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Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC.Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone. Investigator-assessed PFS and blinded independent centrally reviewed PFS were coprimary end points. With 80% power in detecting a 0.60 hazard ratio and two-sided α error of 0.05, 126 events of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17.From April 11, 2016, to February 27, 2019, a total of 160 patients were randomized to erlotinib plus bevacizumab (80) or erlotinib alone (80). At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI]: 12.2-18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI: 8.2-10.6) with erlotinib alone (hazard ratio = 0.66, 95% CI: 0.47-0.92). Blinded independent centrally reviewed PFS analysis confirmed this result. A statistically significant interaction with treatment effect was found for smoking habit (p = 0.0323), with PFS prolongation being clinically significant only among current or previous smokers. Hypertension (grade ≥3: 24% versus 5%), skin rash (grade ≥ 3: 31% versus 14%), thromboembolic events (any grade: 11% versus 4%), and proteinuria (any grade: 23% versus 6%) were more frequent with the combination.The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFR-mutated NSCLC; toxicity was increased with the combination but without unexpected safety issues.

Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of clinical uncertainty about the choice of active treatment in this poor prognosis malignancy.To compare the effectiveness and safety and weigh the benefit of different systemic treatments in patients with pre-treated mesothelioma by systematic review, meta-analysis and network meta-analysis of RCTs. Full-text articles and abstracts were searched on PubMed, EMBASE, Cochrane Library and oncology conferences proceedings from 2005 through November 2021 for phase 2 and 3 RCTs. The protocol was submitted to the PROSPERO registry. Reporting followed the PRISMA guideline. Outcomes of interest were overall survival (OS) and progression-free (PFS), grade ≥3 treatment-related (Tr) adverse events (AEs), Tr-deaths and Tr-AEs leading to treatment discontinuation.Nine trials at low risk of bias by Cochrane Collaboration's methodology were included, encompassing 2789 patients. Five studies showed PFS benefit in the experimental treatment. In two studies, OS was prolonged by immunotherapy (versus placebo) or by adding an antiangiogenic agent to chemotherapy. Reported Tr-AE were lower with single-agent anti-PD1 compared with chemotherapy or placebo. The meta-analysis revealed a beneficial global effect on OS and PFS from experimental treatments (HR 0.86, 95% CI 0.77-0.96, p = 0.0083 and HR 0.79, 95% CI 0.72-0.86, p 0.001), that for the PFS significantly favoured the comparison with non-active treatments (HR 0.73, 95% CI 0.66-0.81, p 0.001). Younger patients (i.e. 65-70 years) appeared to benefit the most in OS (HR 0.71, 95% CI 0.55-0.92, p = 0.04). The risk of serious Tr-AEs and Tr-deaths was not significantly increased by experimental treatments (RR 1.38, 95% CI 0.81-2.35, p = 0.24 and RR 2.07, 95% CI 0.69-6.24, p = 0.19, respectively) that instead increased TrAEs leading to treatment discontinuation (RR 2.9, 95% CI 1.44-6.08, p = 0.003). The network meta-analysis did not identify any superior treatment in PFS.For patients with pre-treated MPM, single-agent anti-PD1 or chemotherapy ± the antiangiogenic agent can be considered active and safe systemic therapeutic options, particularly for younger patients.

Cyclin4/6-dependent kinase inhibitors (CDKIs) plus hormonotherapy currently represent the standard golden treatment for patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor-2-negative (her-2−) advanced breast carcinoma. Among CDKIs, abemaciclib is the most active. No data on the use of abemaciclib in patients with end-stage renal disease (ESRD) exist in the medical literature. Two women with ER+, her-2− metastatic breast cancer received standard hormonal therapy plus abemaciclib 100 mg b.i.d. under strict monitoring for toxicity. Although ESRD exposes patients to a higher risk of toxicity from antineoplastic agents, no unexpected or severe toxicity was recorded in both patients after 9 and 12 months of therapy. In 1 patient, grade 2 diarrhea started after 7 days of therapy and disappeared or was significantly reduced after using loperamide and dietary modifications. Both patients complained of grade 1 asthenia. Hematological parameters were in line with expected toxicity. No cardiovascular or hepatic side effects were observed. This report of two women with metastatic breast cancer suggests the potentially safe use of abemaciclib in ESRD, which should be confirmed in more extensive real-life studies.

Introduction: Bone metastases (BMs) are the common cause of cancer-related pain, as approximately 45% of cancer patients suffer from bone pain (BP). Radiotherapy (RT) is well established as BP treatment strategy; also, other approaches have been shown to be effective in this setting. Radiofrequency thermoablation (RFA) in a combined strategy with RT appears to be feasible and effective in the treatment of metastatic BP ensuring a better quality of life. Aim of this retrospective study was to describe a case series of patients with painful osteolytic lesions at risk of fracture treated with the RFA-RT combined approach, analyzing local control and pain control as outcomes. Methods: Data of all patients with BM treated with combined approach in our center from April 2016 to June 2020 were retrospectively analyzed. Patients underwent RFA followed by cementoplasty on the same day and RT in a second phase. RT dose ranged between 30 and 37.5 Gy in 5/10 fractions. BP was evaluated according to the numeric rating scale (NRS), at the beginning of treatment and at 1, 2, 3, 6, 9, and 12 months from the end of combined treatment. Results: A total of 27 patients were treated from April 2016 to June 2020 with RFA-RT combined approach. The large majority of patients underwent stereotactic body radiotherapy (SBRT) (23/27). All patients experienced an NRS value decrease >2 at 1 month and between the first and second months. NRS mean value reached 0 at 3, 6, 9, and 12 months’ evaluations. Discussion/Conclusion: The results of this retrospective analysis of patients treated with RFA-RT combined approach for BP support its safety and efficacy in terms of pain reduction. SBRT role in this combined approach has to be investigated in randomized trials.

Many cancer patients use integrative therapies with a combination of natural products and diets. In the Western world, integrative medicine is often not shared with oncologists even during antineoplastic treatments. This behavior stems from the unmet needs of cancer patients who may feel oncologists’ underestimation of their symptoms and spiritual aspects. This case report demonstrates the potential harm of inadequate diet and nutraceutical intake in a 68-year-old woman with metastatic estrogen receptor-positive, human epidermal growth factor receptor-2-negative breast cancer. Her care team recommended hormone therapy with abemaciclib plus fulvestrant. Her diarrhea started after 10 days of therapy and did not disappear, despite the use of loperamide, causing a significant reduction in adherence and dose intensity of abemaciclib. The patient finally disclosed to her oncologist she was following a detoxifying diet and taking several nutraceuticals. Her diarrhea was correlated with abemaciclib but most probably exacerbated and prolonged by the diet. Evaluation of disease after 3 months showed progressive disease. Integrative medicine should be in the multidisciplinary management of cancer patients to avoid potentially harmful events and ameliorate patients’ quality of life in a holistic approach.

At present, multidisciplinary tumor boards (MDTB) are considered best practice in oncology. However, web-based virtualization of MDTB may increase participation in meetings, the number of cases discussed, and adherence to guidelines, deliver better treatment, and eventually improve outcomes for patients with prostate cancer.This is an observational study focused on exploring the structuring process and implementing a multi-institutional virtual MDTB in Sicily, Italy. Other endpoints included the analysis of cooperation between participants, adherence to guidelines, patient outcomes, and patient satisfaction.Overall, 126 patients were referred to the virtual MDTB for a total of 302 cases discussed in an 18-month period. Nearly 45% of cases were referred from general hospitals or tertiary centers, 38% from comprehensive cancer centers, and only 17% from academic ones. Most health professional participants (95%) reported eliminating geographical barriers and consequently reducing costs and saving time as key advantages of virtual meetings over face-to-face ones. Using a specifically designed platform for virtual MDTBs was another excellent point, especially to geolocate clinical trials and time-lapse data storage. The majority of referred patients had stage T 3-4 prostate cancer (79%). Overall, 71% of proposals discussed were approved unchanged, while 19% changed after the virtual MDTB discussion. Debated points were mostly radiologic, surgical, medical, or radiation treatment-related issues. In particular, the prescriptive appropriateness of positron emission tomography with 68Ga-prostatic specific membrane antigen, newer drugs, radiation versus surgical approach, stage T3-4 cases, and adjuvant therapy represented the most debated issues. The proposed diagnostic and/or therapeutic options were controlled for adherence to the guidelines and/or updated scientific evidence. Overall, 98% of approved proposals and changes were in line with the guidelines. Overall, most participants felt virtual MDTB was very useful and case discussions led to a major change of strategy in 19% of cases.Virtual MDTBs are a very useful way to achieve best management of prostate cancer while saving time and fostering cooperation.

To date, the virtual multidisciplinary tumor boards (vMTBs) are increasingly used to achieve high-quality treatment recommendations across health-care regions, which expands and develops the local MTB team to a regional or national expert network. This review describes the process of lung cancer-specific MTBs and the transition process from face-to-face tumor boards to virtual ones. The review also focuses on the project organization's description, advantages, and disadvantages. Semi-structured interviews identified five major themes for MTBs: current practice, attitudes, enablers, barriers, and benefits for the MTB. MTB teams exhibited positive responses to modeled data feedback. Virtualization reduces time spent for travel, allowing easier and timely patient discussions. This process requires a secure web platform to assure the respect of patients’ privacy and presents the same unanswered problems. The implementation of vMTB also permits the implementation of networks especially in areas with geographical barriers facilitating interaction between large referral cancer centers and tertiary or community hospitals as well as easier access to clinical trial opportunities. Studies aimed to improve preparations, structure, and conduct of MTBs, research methods to monitor their performance, teamwork, and outcomes are also outlined in this article. Analysis of literature shows that MTB participants discuss 5–8 cases per meeting and that the use of a vMTB for lung cancer and in particular stage III NSCLC and complex stage IV cases is widely accepted by most health professionals.Despite still-existing gaps, overall vMTB represents a unique opportunity to optimize patient management in apatient-centeredapproach.

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.

The use of opioids in cancer survivors with chronic pain raises concerns as it occurs with chronic non-malignant pain .Thus, in some circumstances advanced therapeuthic strategies should be performed to allow pain control for prolonged periods of time We describe a case of a long-survivor patient receiving prolonged opioid therapy. She received multiple opioid rotations or some more complex treatments, including burst of ketamine and midazolam, which allowed to maintain an acceptable pain control for 12 years, despite her poor compliance. Different opioids in different phases were given. A high level of knowledge, experience, and assessment is mandatory to implement of pain management among survivors.

Immunotherapy with antibodies against PD-1 or PD-L1, either alone or in combination with chemotherapy, has revolutionized treatment paradigms of non-small cell lung cancer (NSCLC) patients without oncogenic driver alterations. These agents, namely immune checkpoint inhibitors (ICIs), have also widely demonstrated a remarkable efficacy in locally advanced as well as in early-stage NSCLC. Assessment of tumor PD-L1 expression by immunohistochemistry has entered into routine clinical practice to select patients for immunotherapy, even though its predictive role has long been debated. Despite improved survival outcomes over standard chemotherapy, treatment with ICIs is associated with initial low response rate, with a significant proportion of patients not responding to these agents. Hence, novel appealing predictive biomarkers, such as those related to tumor cell signaling pathways, metabolism or the tumor microenvironment, have emerged as potentially useful to select those patients most likely to benefit from immunotherapy. Moreover, most patients ultimately develop acquired resistance to ICI treatment over time and novel therapeutic strategies are urgently needed to overcome or delay resistance. Herein, we provide an overview on recent advances in immunotherapy in NSCLC, focusing on updated results from studies on ICIs in different disease settings and at different lines of treatment. We further describe currently emerging predictive biomarkers, beyond PD-L1, to optimize patient selection and novel strategies to improve clinical outcomes.

The spread of instant messenger systems provides an excellent opportunity and a helpful tool to healthcare professionals. WhatsApp instant messenger use is widely prevalent among health professionals, cancer patients, caregivers and the general population. It is a quick and easy communication tool that may also be used on personal computers and business purposes. WhatsApp instant messenger and other similar tools may be a very useful complement for e-medicine. Instant messaging systems may be helpful, especially in rural areas, in medium- or low-income countries, or to avoid unnecessary travels, improve knowledge and awareness of cancer, monitor home care and support the delivery of home care. The unregulated use of WhatsApp instant messenger requires sound and shared guidelines to assure impeccable professional service. Although a significant number of papers have investigated the roles of social networks in connecting patients to health professionals, there is still a lack of information and scientific data about their uses, benefits and limitations in connecting health providers only for professional communication. The role of instant messenger systems in cancer practice and research needs to be clarified. In this paper, we report a focus on available data, pros and contras of the unregulated use of WhatsApp instant messaging, in the context of e-medicine, as an interprofessional and doctor/patient communication tool in oncology.

Treatment of advanced non-small cell lung cancer (NSCLC) has radically improved in the last years due to development and clinical approval of highly effective agents including immune checkpoint inhibitors (ICIs) and oncogene-directed therapies. Molecular profiling of lung cancer samples for activated oncogenes, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and BRAF, is routinely performed to select the most appropriate up-front treatment. However, the identification of new therapeutic targets remains a high priority. Recently, MET exon 14 skipping mutations have emerged as novel actionable oncogenic alterations in NSCLC, sensitive to MET inhibition. In this review we discuss: (I) MET gene and MET receptor structure and signaling pathway; (II) MET exon 14 alterations; (III) current data on MET inhibitors, mainly focusing on selective MET tyrosine kinase inhibitors (TKIs), in the treatment of NSCLC with MET exon 14 skipping mutations. We identified the references for this review through a literature search of papers about MET, MET exon 14 skipping mutations, and MET inhibitors, published up to September 2020, by using PubMed, Scopus and Web of Science databases. We also searched on websites of main international cancer congresses (ASCO, ESMO, IASLC) for ongoing studies presented as abstracts. MET exon 14 skipping mutations have been associated with clinical activity of selective MET inhibitors, including capmatinib, that has recently received approval by FDA for clinical use in this subgroup of NSCLC patients. A large number of trials are testing MET inhibitors, also in combinatorial therapeutic strategies, in MET exon 14-altered NSCLC. Results from these trials are eagerly awaited to definitively establish the role and setting for use of these agents in NSCLC patients.

Background/aim Upper limb breast cancer-related lymphedema (BCRL) is a chronic and severe condition affecting a significant percentage of breast cancer survivors. Even though its physiopathology is well-known, there is no worldwide consensus on BCRL evaluation and a gold-standard treatment. This narrative review aims at providing a brief descriptive overview with regard to BCRL treatment modalities. Materials and methods We conducted a literature search within the PubMed database, and 33 articles out of 56 were selected, including reviews, systematic reviews, and meta-analyses aiming find the most updated evidence regarding BCRL treatment modalities. Results Physical exercise (aerobic exercise, resistance exercise, aquatic therapy), bandages, and intermittent pneumatic compression were shown to be most effective in BCRL patients, in terms of swelling reduction in the acute-intensive phase. Furthermore, physical exercise was beneficial also as a maintenance tool. Manual lymphatic drainage demonstrated efficacy in preventing secondary lymphedema if applied immediately after breast cancer surgery or in early phases of BCRL or as a maintenance tool. Complementary procedures such as acupuncture, reflexology, yoga and photo-biomodulation therapy did not show conclusive results in BCRL treatment. Surgery was shown effective in managing symptoms (liposuction), preventing (lymphaticovenular anastomosis) and treating BCRL (vascularized lymph node transfer). Conclusion BCRL is still a challenging condition either for breast cancer survivors and clinicians, deeply impacting patient functioning and quality of life. Due to the lack of globally accepted criteria in evaluating BCRL, to date a gold standard treatment for this widespread issue is still needed.

BACKGROUND Multidisciplinary tumor boards play a pivotal role in the patient-centered clinical management and in the decision-making process to provide best evidence-based, diagnostic, and therapeutic care to patients with cancer. Among the barriers to achieve an efficient multidisciplinary tumor board, lack of time and geographical distance play a major role. Therefore, the elaboration of an efficient virtual multidisciplinary tumor board (VMTB) is a key point to successfully obtain an oncology team and implement a network among health professionals and institutions. This need is stronger than ever during the COVID-19 pandemic. OBJECTIVE This paper presents a research protocol for an observational study focused on exploring the structuring process and the implementation of a multi-institutional VMTB in Sicily, Italy. Other endpoints include analysis of cooperation between participants, adherence to guidelines, patients’ outcomes, and patient satisfaction. METHODS This protocol encompasses a pragmatic, observational, multicenter, noninterventional, prospective trial. The study’s programmed duration is 5 years, with a half-yearly analysis of the primary and secondary objectives’ measurements. Oncology care health professionals from various oncology subspecialties at oncology departments in multiple hospitals (academic and general hospitals as well as tertiary centers and community hospitals) are involved in a nonhierarchic manner. VMTB employs an innovative, virtual, cloud-based platform to share anonymized medical data that are discussed via a videoconferencing system both satisfying security criteria and compliance with the Health Insurance Portability and Accountability Act. RESULTS The protocol is part of a larger research project on communication and multidisciplinary collaboration in oncology units and departments spread in the Sicily region. The results of this study will particularly focus on the organization of VMTBs, involving oncology units present in different hospitals spread in the area, and creating a network to allow best patient care pathways and a hub-and-spoke relationship. The present results will also include data concerning organization skills and pitfalls, barriers, efficiency, number, and types with respect to clinical cases and customer satisfaction. CONCLUSIONS VMTB represents a unique opportunity to optimize patient management through a patient-centered approach. An efficient virtualization and data-banking system is potentially time-saving, a source for outcome data, and a detector of possible holes in the hull of clinical pathways. The observations and results from this VMTB study may hopefully be useful to design nonclinical and organizational interventions that enhance multidisciplinary decision-making in oncology. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/26220

Background Multidisciplinary tumor boards play a pivotal role in the patient-centered clinical management and in the decision-making process to provide best evidence-based, diagnostic, and therapeutic care to patients with cancer. Among the barriers to achieve an efficient multidisciplinary tumor board, lack of time and geographical distance play a major role. Therefore, the elaboration of an efficient virtual multidisciplinary tumor board (VMTB) is a key point to successfully obtain an oncology team and implement a network among health professionals and institutions. This need is stronger than ever during the COVID-19 pandemic. Objective This paper presents a research protocol for an observational study focused on exploring the structuring process and the implementation of a multi-institutional VMTB in Sicily, Italy. Other endpoints include analysis of cooperation between participants, adherence to guidelines, patients’ outcomes, and patient satisfaction. Methods This protocol encompasses a pragmatic, observational, multicenter, noninterventional, prospective trial. The study’s programmed duration is 5 years, with a half-yearly analysis of the primary and secondary objectives’ measurements. Oncology care health professionals from various oncology subspecialties at oncology departments in multiple hospitals (academic and general hospitals as well as tertiary centers and community hospitals) are involved in a nonhierarchic manner. VMTB employs an innovative, virtual, cloud-based platform to share anonymized medical data that are discussed via a videoconferencing system both satisfying security criteria and compliance with the Health Insurance Portability and Accountability Act. Results The protocol is part of a larger research project on communication and multidisciplinary collaboration in oncology units and departments spread in the Sicily region. The results of this study will particularly focus on the organization of VMTBs, involving oncology units present in different hospitals spread in the area, and creating a network to allow best patient care pathways and a hub-and-spoke relationship. The present results will also include data concerning organization skills and pitfalls, barriers, efficiency, number, and types with respect to clinical cases and customer satisfaction. Conclusions VMTB represents a unique opportunity to optimize patient management through a patient-centered approach. An efficient virtualization and data-banking system is potentially time-saving, a source for outcome data, and a detector of possible holes in the hull of clinical pathways. The observations and results from this VMTB study may hopefully be useful to design nonclinical and organizational interventions that enhance multidisciplinary decision-making in oncology. International Registered Report Identifier (IRRID) DERR1-10.2196/26220

Chemotherapy-induced nausea and vomiting (CINV) may affect adherence to planned chemotherapy treatments and compromise patients' quality of life during the therapy. NEPA is an oral fixed combination of netupitant, a highly-selective NKEligible patients were undergoing carboplatin and gemcitabine combination chemotherapy for metastatic non-small cell lung cancer (NSCLC), ovarian cancer or urothelial cancer and experienced nausea and/or vomiting after the first cycle of chemotherapy, despite an antiemetic prophylaxis with a 5HTDuring the first cycle of chemotherapy, 15 out of 30 (50%) patients did not properly control CINV with a 5HTOur experience showed that NEPA has proven to be very effective and well tolerated in the prophylaxis of CINV induced by carboplatin-based chemotherapy.

Fighting cancer is an economically expensive challenge for both health care payers, and the patients and their families and the median costs for cancer care are rapidly increasing in the last decade. Although both direct and indirect costs of medical assistance have been a frequent source of distress and contention, however analysis of the non-medical expenses incurred directly by cancer patients has not received adequate attention. Developing a deeper understanding of so-called "out-of-pocket" costs may be necessary. Out-of-pocket costs for medical care range from 7 % to 11 % of medical costs for all payers. However, the range of out-of-pocket costs shows considerable variability in different studies. In this review, we reviewed available data concerning direct and indirect medical costs, including psychosocial ones.

Objectives Data supporting the prognostic role of chemotherapy induced haematological toxicity suggest that toxicity-adjusted-dosing (TAD) of chemotherapy might improve treatment efficacy. We tested whether TAD of the cisplatin-etoposide combination might improve the response rate, in previously untreated extensive stage disease (ED)-SCLC patients, as compared with standard fixed-dosing (FD). Methods Patients with ED-SCLC were randomized to receive either TAD or FD of cisplatin-etoposide as first-line treatment. Primary endpoint was the objective response rate (ORR) according to the RECIST 1.0 criteria, secondary endpoints included progression free survival (PFS), overall survival (OS) and toxicity. Results Hundred-fifty-eight patients were randomized. Most patients were male, with ECOG-PS 1, without brain metastases and had not received radiotherapy before study entry. Response rate was 54.4 (95%CI: 43.5–64.9%) and 58.2 (95%CI: 47.2–68.5%) in the control and experimental arms, respectively (P = 0.75). No significant differences were found in terms of PFS (HR 1.04; 95%CI: 0.74–1.44, P = 0.84) and OS (HR1.01; 95%CI 0.71–1.42, p = 0.97). Seven patients died on treatment, one in the standard arm and 6 in the experimental arm. The most frequent cause of death was neutropenia with infection and, apart in one, death was not related to dose modification. Severe toxicity was more frequent in the experimental arm (91% vs 60%). Conclusions In our population of chemonaive ED SCLC patients, TAD failed to improve the ORR, PFS and OS over the FD of cisplatin-etoposide as first line chemotherapy and was associated with increased toxicity.

// Lucia Kim 1,12,* , Mauro Saieg 1,13,* , Massimo Di Maio 2,14,* , Ciro Gallo 3,* , Charles Butts 4 , Fortunato Ciardiello 5 , Ronald Feld 6 , Dengxiao Cheng 6 , Vittorio Gebbia 7 , Marco Angelo Burgio 8 , Yasmin Alam 9 , Simona Signoriello 3 , Antonio Rossi 10 , Natasha Leighl 6 , Paolo Maione 10 , Alessandro Morabito 2 , Geoffrey Liu 6,** , Ming-Sound Tsao 1,** , Francesco Perrone 2,** and Cesare Gridelli 10,11,** 1 Department of Pathology, University Health Network, Princess Margaret Cancer Center and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 2 National Cancer Institute, G. Pascale Foundation, IRCCS, Naples, Italy 3 Department of Mental Health and Preventive Medicine, Chair of Statistics, Second University of Naples, Naples, Italy 4 Medical Oncology, Cross Cancer Institute, Edmonton, Canada 5 Medical Oncology, Second University, Naples, Italy 6 Division of Hematology and Oncology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada 7 Medical Oncology, Casa di Cura La Maddalena, Palermo, Italy 8 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy 9 Medical Oncology, Windsor Regional Cancer Centre, Windsor, Canada 10 Department of Oncology/Hematology, Division of Medical Oncology, “S.G. Moscati” Hospital, Avellino, Italy 11 On behalf of the TORCH Investigators 12 Department of Pathology, Inha University School of Medicine, Incheon, South Korea 13 Santa Casa Medical School, Sao Paulo, SP, Brazil 14 University of Turin, Turin, Italy * Co-first author ** Co-last author Correspondence to: Cesare Gridelli, email: // Keywords : NSCLC, EGFR TKI, biomarker analysis, predictive factors, prognostic factors Received : November 09, 2016 Accepted : February 01, 2017 Published : February 25, 2017 Abstract Background: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. Methods: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting. Progression-free survival (PFS) was the primary end-point, overall survival, response rate and side effects (diarrhoea and skin toxicity) were secondary end-points. Interactions between biomarkers and treatment were studied with multivariable models (either Cox model or logistic regression). Statistical analyses accounted for multiple comparisons. Results: At least one biomarker was assessed in 324 out of 760 patients in the TORCH study. EGFR mutation was more common in female ( P = 0.0001), East Asians ( P < 0.0001) and never smoker ( P < 0.0001) patients; low MET protein expression by IHC (H-score

Background: Agent targeting HER-2 pathway plus chemotherapy has represented a major progress in the management of patients with breast cancer. However, the role of late-line treatment in heavily pretreated patients is still largely unclear. In the last decade, nab-paclitaxel has shown significant activity and good toxicity profile in metastatic breast cancer. Case Presentation: We report the case of a 76-year-old Caucasian woman with metastatic HER-2 positive ductal infiltrating breast carcinoma treated with a combination of weekly nab-paclitaxel and trastuzumab as fifth-line therapy. She had previously received first-line paclitaxel and trastuzumab, second-line vinorelbine and trastuzumab, third-line TDM1 and fourth-line oral capecitabine and lapatinib. Clinical and radiological staging showed progression at bone, skin and soft-tissue. The patient received weekly nab-paclitaxel plus trastuzumab. Massive objective response was clinically and PET documented which lasted 8 months. Tolerance to treatment was fairly good as well as cardiac safety. Conclusion: To the best of our knowledge, this is the first reported case of efficacy of nab-paclitaxel in combination with trastuzumab as fifth-line of treatment in a patient with metastatic HER-2 positive breast cancer.

The authors present a case of an 80-year-old Caucasian male with multiple gastric and rectal metastases from malignant melanoma presenting with hypochromic anemia as the sole symptom of disease without evidence of cutaneous and ocular tumor localization. The patient had a medical history positive for malignant lentigo melanoma of the occipital region of the scalp and early stage laryngeal squamous cell carcinoma and prostatic carcinoma treated with radiation therapy. The authors make some considerations on intestinal involvement by metastatic melanoma and discuss the choice of not treating with endoscopic procedures the gastric metastatic lesions most likely responsible for the clinical sign present at diagnosis. The patient was referred to clinical oncologists and received immunotherapy with ipilimumab and pembrolizumab.

Introduction: Radium-223 (223Ra) improves symptoms and survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC). Study aim: To evaluate the impact of a previous radical prostatectomy (RP) on the outcome of 223Ra therapy in mCRPC patients. The primary prostate tumor left untreated could progress during 223Ra treatment. Materials and methods: mCRPC symptomatic patients treated with 223Ra were enrolled. Luteinizing Hormone-Releasing Hormone analogue was maintained. No other anticancer therapy was given. 223Ra was administered i.v. at the dose of 55 kBq/kg every 4 weeks for 6 cycles. Patients were stratified according to previous RP or not. Hematological toxicity was monitored. Statistical analysis of 223Ra discontinuations, progressions, and deaths were performed. Results: Forty-four patients were enrolled, 16 (36.4%) previously received RP, 5 (11.3%) prostate radiotherapy and 23 (52.3%) maintained the primary prostate tumor after local treatment. All patients presented only bone metastases, 24 patients (54.5%) had more than 20. Twenty-six (59.1%) patients were treated after first or second line systemic chemotherapy. Treatment interruptions occurred in 14 patients (50%) with prostate and in 4 (25%) without (P = 0.04). After a median follow-up of 18 months (6−30 months), 15 (53.6%), and 7 (43.7%) progressions (P = 0.34) and 13 and 1 (6.2%) deaths (P = 0.04) occurred in patients with and without prostate respectively. Conclusion: The presence of the primary prostate tumor seems to play a detrimental role in mCRPC patients undergoing 223Ra treatment in absence of other concomitant anticancer therapy. On the other hand a previous RP might play a protective role. 2019 Elsevier Inc. All rights reserved.

e19389 Background: Financial toxicity (FT) among cancer patients (CP) is multifactorial, arising from both disease-related and non- disease related factors, including socio-cultural, environmental, and psychological attributes. It derives both from costs related to assistance and borne on the patients and its caregivers, and reduction of income capacity also in this case borne on the patients and on the caregivers. Stress levels may escalate to significant proportions in some patient, to present with symptoms of anxiety especially during therapy administration periods. Methods: In order to highlight financial toxicity related to the diagnosis of metastatic pancreatic and lung cancer and to measure its evolution over time and any correlation with the prognosis, we developed a questionnaire called FT16 and we conducted a validation study on a sample of 31 patients. The design of the study involved the development and the psychometric assessment of a scale to measure the perceived sources of FT among CP. Following extensive literature review, a table of specification with the initial items was created to guide item construction for developing the scale. The items related to these FT were converted into an 16-item, multipoint questionnaire, resulting in the FT16. We also monitored quality of life of the patients, using the QlQ C-30 questionnaire, in the aim to capture correlation between FT onset and quality of life deterioration; clinical characteristics of the patients, response to therapy and outcome parameters also have been recorded in the aim to evaluate eventual correlation with FT. Results: The questionnaire was administered to 31 adult patients with lung and pancreatic metastatic cancer, both men and women, who were newly diagnosed and will undergo cancer treatment. Each of them has been informed about the research and written informed consent has been obtained. The internal consistency reliability (Cronbach’s alpha) was 0.77 for the 16 items of the FT16. Analyses of variance (ANOVAs) indicated that there were no significant differences in the mean FT16 score, between sexes, and age groups in the severity score. Conclusions: FT16 questionnaire seems to be an useful tool to capture FT onset in this poor-prognosis subset of patients; the analysis of the data recorded will continue to assess the capability of the FT16 to capture correlations with clinical characteristics at diagnosis and correlations with the prognosis.

e21580 Background: EGFR tyrosine kinase inhibitors (TKIs) represent the standard first-line therapy for advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, despite initial marked responses, tumors invariably develop acquired resistance to TKIs. Oligoprogression is commonly observed during treatment with oncogene-directed therapies, including EGFR TKIs, and refers to patients who experience disease progression only in limited sites as a result of heterogeneous mechanisms of resistance. The use of local ablative treatments for these resistant lesions may extend the duration of TKI therapy and potentially improve long-term disease control and survival. We e retrospectively analyzed the efficacy of EGFR TKI therapy continuation with high-dose hypofractionated radiation therapy (RT), in EGFR-mutant NSCLC patients with oligoprogressive disease. Methods: Patients with metastatic EGFR mutant NSCLC who developed oligoprogression during first-line treatment with gefitinib were included in this analysis. We evaluated progression-free survival 1 (PFS 1), defined as the time from initiation of TKI therapy until development of oligoprogression or death, and PFS 2, defined as time of focal progression until further progression of disease or death. Overall survival and safety were also assessed. Results: Thirty-six patients were included in the study. The median PFS 1 was 12.5 (4.0-23.2) months. High-dose hypofractionated RT consisted of intensity-modulated RT in 23 patients (64%) and stereotactic radiotherapy in 13 cases (36%). The median PFS 2 was 6.3 (2-12.5) months. Overall survival was 38.7 months (9.0-46.3). The treatment was well-tolerated and no patient had to discontinue TKI therapy because of adverse events during radiotherapy. Conclusions: Our therapeutic strategy, including high-dose hypofractionated RT in addition to TKI therapy, was feasible in the clinical setting and was associated with significant prolongation of disease control and improvement of survival outcomes, while being associated with manageable side effects. Our study further support the use of definitive therapeutic approaches in oligoprogressive disease, especially in oncogene-driven tumors. Molecular profiling of metastatic sites remains crucial to identify novel biomarkers, involved in the development of acquired resistance and oligoprogression, that may be useful to select patients for local treatments.

Introduction Cisplatin with pemetrexed (CP) and carboplatin with paclitaxel and bevacizumab (CbTB) are standard first-line treatments for patients with advanced nonsquamous (NS) non–small-cell lung cancer (NSCLC). Quality of life (QoL) is a key objective in the management of advanced NSCLC. Thus, effect on QoL could be an additional factor in the choice of treatment. Patients and Methods Patients with untreated stage IIIB/IV NS-NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomized to receive first-line chemotherapy with cisplatin 75 mg/m 2 and pemetrexed 500 mg/m 2 , every 3 weeks, for 6 cycles followed by maintenance pemetrexed; or carboplatin area under the curve 6, paclitaxel 200 mg/m 2 , and bevacizumab 15 mg/kg, every 3 weeks, for 6 cycles followed by maintenance bevacizumab. The primary end point was the difference in QoL between the 2 treatment arms after 12 weeks of maintenance, measured using the EuroQoL 5 Dimensions-Index (EQ5D-I) and EQ5D-visual analogue scale (EQ5D-VAS). Results One hundred eighteen patients were randomized to CP (n = 60) or CbTB (n = 58). Baseline characteristics were well balanced. The proportion of patients evaluable for the primary end point was lower than planned. After 12 weeks of maintenance, the difference between mean changes in EQ5D-I was 0.137, favoring CP (95% confidence interval [CI], −0.02 to 0.29, Wilcoxon P = .078), although not statistically significant; and the difference between mean changes in EQ5D-VAS was 0.97 (95% CI, −9.37 to 11.31, Wilcoxon P = .41). Conclusion Although the study was underpowered because of a small number of patients evaluable for the primary end point, QoL did not differ between treatment arms. Other factors such as comorbidities and schedule should be used when deciding on first-line treatment.

Background In Italy, previously untreated patients with RAS wild-type metastatic colorectal cancer (mCRC) may receive an epidermal growth factor receptor (EGFR) inhibitor with a chemotherapy regimen (CT). The choice of anti-EGFR, either cetuximab (cet+CT) or panitumumab (pan+CT), depends on various factors, including adverse event (AE) profiles. Although AE profiles will evolve with increasing use and familiarity, the differences in AE profiles can be explored using literature and safety data from the summary of product characteristics (SmPC). The financial impact of these differences on the Italian National Health Service has yet to be estimated. Methods We developed a model to estimate costs of AE management. Frequencies of common and very common AEs associated with cet+CT or pan+CT were sourced from the respective SmPC.1,2 Applicable resource use costs were obtained from hospital services price lists from the Ministry of Health using the DRG outpatient tariff.3 The national-level financial impact was calculated from the number of cet+CT–eligible patients with mCRC treated in the first line based on published literature, national guidelines, and pan+CT market share. Inputs were validated by practicing Italian oncologists. Results All-grade AEs were estimated to be 58.1% lower and grade 3/4 AEs were estimated to be 70.2% lower in patients receiving cet+CT than in those receiving pan+CT. Mean costs of AE management per patient treated with cet+CT and pan+CT were estimated at €1,194 and €2,951, respectively, resulting in average savings of €1,758 (59.6%) per patient. Differences are mainly driven by a lower frequency of AEs that are costly to manage, such as GI disorders. Annual savings could reach €2,191,839 for a population of 1,247 cet+CT–eligible patients with mCRC. Conclusions Fewer AEs for cet+CT may result in markedly lower AE management costs vs pan+CT. Although results should be considered together with overall costs and clinical outcomes, cet+CT could decrease cost burden on the Italian National Health Service and AE burden for patients with mCRC. Editorial acknowledgement ClinicalThinking, Inc, Hamilton, NJ, USA (funded by Merck Healthcare KGaA, Darmstadt, Germany). Legal entity responsible for the study Merck Healthcare KGaA. Funding Merck Healthcare KGaA. Disclosure N. Personeni: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono. V. Gebbia: Honoraria (self): Merck; Honoraria (self): Amgen; Honoraria (self): Roche. P. Novelli: Full / Part-time employment: Merck Serono S.p.A. S. Di Matteo: Research grant / Funding (institution): Merck. G. Colombo: Research grant / Funding (institution): Merck. C. Pescott: Full / Part-time employment: Merck Healthcare KGaA. All other authors have declared no conflicts of interest.

Background: In vitro data suggest that panobinostat (LBH589), a pan-deacetylase inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer (SCLC) with regression of tumors. Methods: This multicenter, nonrandomized phase 2 trial was designed to evaluate antitumor activity of LBH589 in patients with previously treated SCLC. Patients received LBH589 administered intravenously at a dose of 20 mg/mq (days 1–8) every 21 days. Results: A total of 21 patients with extensive- or limited-stage SCLC were enrolled. Patients received a median of two cycles (range, 1–6). LBH589 was well tolerated, and the most common toxicities were grade 1 to 2 gastrointestinal disorders (nausea 38%, diarrhea 24%, vomiting 19%), grade 1 to 2 thrombocytopenia (14.3%). Of 19 patients evaluable for efficacy, two cases showed shrinkages more than 30% at first assessment, with time to progression of 14 and 21 weeks, respectively, and there were three long disease stabilizations of 12, 10, and 13 weeks. The study was prematurely closed because of a lack of activity. Conclusion: This is the first report of a pan-deacetylase inhibitor inducing tumor shrinkage and sustained stable disease in SCLC. We believe that although the trial was prematurely discontinued, modest clinical activity of LBH589 combined with a favorable safety profile in pretreated SCLC patients was observed, which warrants further exploration of the potential contribution of LBH589 in other trials.

BACKGROUND: This survey was performed to draw information on pain prevalence, intensity, and management from a sample of patients who were admitted to an oncologic center where a palliative care unit (PCU) has been established for 13 years. METHODS: Cross-sectional survey in an oncological department performed 1 day per month for six consecutive months. RESULTS: Of the 385 patients, 69.1, 19.2, 8.6, and 3.1 % had no pain, mild, moderate, and severe pain, respectively. Inpatients and patients with a low Karnofsky score showed higher levels of pain intensity (p

Background Adherence to erlotinib could be a determinant for clinical outcome and treatment toxicity in patients with advanced non–small-cell lung cancer (A-NSCLC). Patients and Methods In an observational study, the Basel Assessment of Adherence Scale (BAAS), a visual analogue scale (VAS), pill counting, and missed appointment rate were used to evaluate adherence in a first cohort of patients who was prescribed erlotinib without a specifically designed management strategy and in a second cohort of patients followed by an oral treatment monitoring program. Results Adherence > 95% by BAAS at 2 months of treatment in the first and second cohorts was 72% and 84%, respectively ( P = .042). Adherence by pill counting was 78% and 87% in the first and second cohorts, respectively ( P = .0021). Disease control rate (DCR) (complete response [CR] + partial response [PR] + stable disease [SD]) was significantly higher in all patients whose adherence by BAAS at 2 months was ≥ 95% ( P = .0266). DCR was higher in the second cohort compared with the first, being 63% (95% confidence interval [CI], 53%-72%) and 44% (95% CI, 30%-58%) in the second and the first cohort, respectively ( P = .0368). A significant correlation between the number of adverse events and patient-reported adherence was observed ( r = 0.105; P = .0001). Conclusion Nonadherence may be related to poorer rates of response to erlotinib. Effective interventions to reduce nonadherence need to be implemented.

Background The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. Methods EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting. Progression-free survival (PFS) was the primary end-point, overall survival, response rate and side effects (diarrhoea and skin toxicity) were secondary end-points. Interactions between biomarkers and treatment were studied with multivariable models (either Cox model or logistic regression). Statistical analyses accounted for multiple comparisons. Results At least one biomarker was assessed in 324 out of 760 patients in the TORCH study. EGFR mutation was more common in female (P = 0.0001), East Asians (P < 0.0001) and never smoker (P < 0.0001) patients; low MET protein expression by IHC (H-score

In the nineties, spinal analgesia has been described as an useful means to control pain in advanced cancer patients. The aim of this review was to update this information with a systematic analysis of studies performed in the last 10 years. 27 papers pertinent with the topic selected for review were collected according to selection criteria. Few studies added further information on spinal analgesia in last decade. Despite a lack of a clinical evidence, spinal analgesia with a combination of opioids, principally morphine, and local anesthetics may allow to achieve analgesia in patients who had been intensively treated unsuccessfully with different trials of opioids. Some adjuvant drugs such as clonidine, ketamine, betamethasone, meperidine, and ziconotide may be promising agents, but several problems have to be solved before they can be used in the daily practice. In complex pain situations, spinal analgesia should not be negated to cancer patients, and oncologists should address this group of patients to other specialists.

Introduction: To date, orally administered chemotherapy and biologic agents represent a significant percentage of all antineoplastic treatments in several types of cancer, which are most likely to increase in the near future. In this scenario, the issue of adherence and persistence to oral therapy is a key issue since poor compliance to oral antineoplastic treatments may negatively influence patients' clinical outcomes and, in turn, cause an increase in costs, number of hospitalizations and time spent in the hospital. Areas covered: The issue of adherence to new oral chemotherapeutic and/or biologic agents has not been deeply evaluated and data published in medical literature are quite scarce. Adherence is a multidimensional phenomenon, which may be influenced by patient-and health-care provider-related factors, anticancer therapy itself, education and socioeconomic aspects. Patients' selection plays, therefore, a key role in maximizing adherence and persistence to oral therapies. Treating health-care practitioners should first evaluate patient reliability to avoid prescribing oral treatments to patients with socioeconomic and medical conditions, which may predict poor adherence. Expert opinion: Adherence and persistence to new oral biologic agents, which are linked to several side effects and whose use is constantly widening, should represent a main endpoint of clinical research in the nearest future. © 2012 Informa UK, Ltd.

Lung cancer is the most common cancer in the world today, in terms of both incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and the majority of people diagnosed with NSCLC have locally advanced or metastatic disease. Treatment algorithms have rapidly changed in the last 10 years because of the introduction of new chemotherapeutic and targeted agents in clinical practice. SUN is a 1-year longitudinal observational multicenter study that has consecutively enrolled patients affected by stage IIIB or IV NSCLC with the aim to describe the pattern of care and evolving approaches in the treatment of advanced NSCLC. 987 consecutive NSCLC patients were enrolled between January 2007 and March 2008 at the 74 participating centers throughout Italy and a 12-month follow-up was performed. Cyto-histological diagnosis was performed mainly by broncoscopy with only 24% by CT-scan guided fine-needle aspiration biopsy. 91.4% of the patients received a first-line medical treatment and 8.6% supportive care only. Median age of patients receiving first-line treatment was 66 years. First-line chemotherapy consisted of a single agent in 20% of patients and combination chemotherapy in 80%. The most frequently used chemotherapy regimens were cisplatin plus gemcitabine and carboplatin plus gemcitabine. Median survival of patients receiving first-line chemotherapy was 9.1 months. 32% percent of patients received a second-line treatment that consisted of chemotherapy in 71% of cases and erlotinib in 29%. Overall third-line treatment was given to 7.3% of patients. These results showed a pattern of care for advanced NSCLC that reflects the current clinical practice in Italy at the study time with a high adherence to the International guidelines by the Italian Oncologists. Keywords Advanced NSCLC; Observational study; Chemotherapy; Platin-based chemotherapy; Pemetrexed; Docetaxel; Targeted therapy; Erlotinib

The aim of this study was to determine the activity and toxicity of two sequential chemotherapy regimens in the first-line treatment of advanced non-small-cell lung cancer (NSCLC).Eighty-eight chemonaive patients with stage IIIB/IV NSCLC were randomised to receive either three cycles of 75 mg/m(2) cisplatin plus 75 mg/m(2) docetaxel, both administered on day 1 every 21 days, followed by three cycles of 1,200 mg/m(2) gemcitabine on days 1 and 8 every 3 weeks (arm A), or three cycles of 25 mg/m(2) cisplatin plus 25 mg/m(2) docetaxel on days 1, 8 and 15 every 28 days, followed by three cycles of 1,200 mg/m(2) gemcitabine on days 1 and 8 every 3 weeks (arm B).Of the evaluable patients, 61% in arm A (n = 41) and 36% (n = 44) in arm B completed treatment as per the protocol. The best tumour response rates were as follows (arm A and arm B): complete response: 2.4 and 2.3%; partial response: 39 and 20.4%; stable disease: 26.8 and 13.6%; and progressive disease: 31.8 and 45.4%. The median progression-free and overall survival were 3.9 and 12.3 months in arm A, respectively, 3.1 and 7.7 months in arm B. Grade 3-4 adverse events were more common in arm A. Grade 3-4 neutropenia was the main toxicity observed (56.1% in arm A and 11.4% in arm B).Our data demonstrate the feasibility of a sequential approach of cisplatin plus docetaxel followed by single-agent gemcitabine. Weekly administration of platinum-docetaxel is associated with an improved safety profile but lower efficacy than the conventional three-weekly schedule (registration ID 2004-001044-72).

Background More than 50% of brain metastases (BMs) occur in advanced non-small cell lung cancer (NSCLC) patients. Untreated patients with BMs have a poor prognosis with a median survival of 2 months. In most cases BMs are multiple and their optimal therapy is whole-brain radiation therapy (WBRT). The role of systemic therapies for these patients is still a matter for investigation due to concerns about the ability of these drugs to cross the blood–brain barrier (BBB). Cisplatin (CDDP) remains the backbone for medical treatment of NSCLC and fotemustine (FTM) is a nitrosurea able to cross the BBB. Methods Patients with advanced NSCLC, ECOG performance status (PS) 0–1 and multiple BMs not amenable to surgery or stereotactic radiotherapy were treated with 2 cycles of FTM 80 mg/m2 days 1, 8 and CDDP 80 mg/m2 day 1, every 3 weeks followed by WBRT 30 Gy (3 Gy daily in 10 fractions). Radiological restaging was performed before WBRT to assess the role of chemotherapy both for cranial and extracranial disease. Patients with disease control (DC: complete response plus partial response) received 4 more cycles. To assess the basic activities of daily living (ADL), the Barthel ADL Index was used to score patients’ performance every 2 cycles. The trial design provides a two-step evaluation according to the optimal two-stage design of Simon. In the first phase 29 patients were enrolled in order to verify if this schedule showed more than 25% response rate both for cranial and extracranial disease. If so, enrolment added up to a total of 81 patients. Results After the first evaluation 4 out of 29 patients were excluded from the study (3 untreated/1 not included for administrative reasons). At the time of the planned interim analysis patient's characteristics were the following: median age 61 years (range 44–70), M/F = 16/9, adenocarcinoma 11, squamous 5, large cell 2, undefined NSCLC 7; PS 0/1 in 11/14 cases, median Barthel Index score was 20 [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] . Three (12%) partial responses were observed, 9 subjects (36%) with stable disease and 13 (52%) showing disease progression. These data did not satisfy the pre-planned hypothesis and the study was stopped. At the time of the first evaluation before WBRT 12/25 (48%) patients had a systemic DC in contrast with 15/25 (60%) patients with BMs DC. Chemotherapy was relatively well tolerated with a prevalence of asthenia as the most relevant specific toxicity while the haematological toxicity was mild. Conclusion CDDP and FTM combined with WBRT do not represent a therapeutic option for patients with NSCLC. Therefore further studies to evaluate the combination of systemic treatments with WBRT are warranted.

at present, there is very little data available about the impact of anemia on elderly cancer patient's quality of life (QoL). Most of the acquired knowledge has been derived from small studies selected for primary site cancer. This observational study investigates the association between hemoglobin (Hb) level and comprehensive geriatric assessment variables: Cancer Linear Analog Scale (CLAS), Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE) in elderly cancer patients undergoing chemotherapy (CT).we enrolled 586 elderly cancer patients undergoing CT who were evaluated at baseline and every 3-4 weeks for at least 12 weeks. The correlation between Hb level changes and the examined index changes were performed using Pearson correlation analysis and a multivariate analysis was performed using a logistic regression model.both univariate and multivariate analyses at baseline showed that Hb values are related to ECOG performance status (PS), stage of disease and self-reported QoL. Hb level variation significantly correlated with CLAS and ADL changes measured at baseline and after 12 weeks. This correlation is highly significant in patients with Hb11g/dl. Multivariate analysis showed that Hb change of at least 1g/dl was the only independent predictor of a better quality of life, when assessed by using the CLAS and ADL questionnaire (p0.05). Moreover the median time of hospitalisation was found to be significantly lower in patients showing higher Hb level (Hb ≥ 11g/dl) (p=0.037).the findings of this study seem to provide adequate support for the correlation between anemia and elderly cancer patient's QoL. Interestingly, we reported an association between anemia and the length of hospitalisation in this setting of patients. However, the above results do need to be confirmed by further prospective trials.

Introduction: Several large randomized trials have shown the superiority of combining trastuzumab with chemotherapy versus chemotherapy alone as adjuvant treatment for HER2+ breast cancer patients. We are running a large phase III trial comparing two different trastuzumab durations (Short-HER study). We are reporting the preliminary cardiac safety data. Methods: The Short-HER study is a phase III, multicentric, Italian trial where 2500 HER2+ breast cancer patients will be randomized to: Arm A (Long) 4 courses of anthracycline based chemotherapy (AC or EC) followed by 4 courses of docetaxel in combination with trastuzumab, followed by 14 additional courses of 3-weekly trastuzumab; or Arm B (Short) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab followed by FEC x3. this is a non-inferiority trial with DFS and OS as primary end points, and 2-yr failure rate and incidence of cardiac events as secondary end points. Left ventricular ejection fraction (LVEF) is measured at baseline, at the end of each sequence of chemotherapy in both arms, and after 9 and 12 months since randomization thereafter. A cardiac event (CE) was defined as the occurrence of any of the followings: 1) LVEF decrease of more than 15 percentage points from baseline ; 2) LVEF decrease of more than 10 percentage points with absolute value below 50%; 3) symptomatic cardiac failure; 4) other cardiac side effects of grade 2 or more. Results: 510 patients from 69 Italian centers have been randomized so far, 251 in arm A (long) and 259 in Arm B (Short). 146 patients enrolled in arm A and 150 patients enrolled in arm B have received at least 3 months of therapy, and are eligible for the present analysis. In arm A (long), 20 patients (13.7%) experienced a CE: 12 patients experienced a LVEF decline of > 15 percentage points (5 patients with LVEF below 50%, one patient with concomitant atrial fibrillation); 3 patients had a LVEF decline of >10 percentage points with an absolute value below 50%. One patient had symptomatic cardiac failure. Two patients developed Grade 2 hypertension. Two patients developed Grade 2 arrhythmia. In arm B (short), 11 patients (7.3%) experienced a CE: 7 patients had a LVEF decline of > 15 percentage points; one patient had a LVEF decline of > 10 percentage points with an absolute value below 50%. Three patients developed Grade 2 arrhythmia Conclusions: This is a non-inferiority study designed on the assumption that a shorter treatment duration is associated with a significantly lower incidence of cardiac events. With 9 clinically relevant CEs (symptomatic cardiac failure or LVEF below 50%) in arm A (Long) and 1 in arm B (Short), these preliminary data support the assumption, and recruitment is ongoing. Supported by Agenzia Italiana del FArmaco (AIFA). Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-12-05.

The use of oral anticancer drugs has shown a steady increase. Most patients prefer anticancer oral therapy to intravenous treatment primarily for the convenience of a home-based therapy, although they require that the efficacy of oral therapy must be equivalent and toxicity not superior than those expected with the intravenous treatment. A better patient compliance, drug tolerability, convenience and possible better efficacy for oral therapy as compared to intravenous emerge as the major reasons to use oral anticancer agents among oncologists. Inter- and intra-individual pharmacokinetic variations in the bioavailability of oral anticancer drugs may be more relevant than for intravenous agents. Compliance is particularly important for oral therapy because it determines the dose-intensity of the treatment and ultimately treatment efficacy and toxicity. Patient stands as the most important determinant of compliance. Possible measures for an active and safe administration of oral therapy include a careful preliminary medical evaluation and selection of patients based on possible barriers to an adequate compliance, pharmacologic issues, patient-focused education, an improvement of the accessibility to healthcare service, as well as the development of home-care nursing symptom-focused interventions. Current evidences show similar quality of life profile between oral and intravenous treatments, although anticancer oral therapy seems to be more convenient in terms of administration and reduced time lost for work or other activities. Regarding cost-effectiveness, current evidences are in favor of oral therapy, mainly due to reduced need of visits and/or day in hospital for the administration of the drug and/or the management of adverse events. © 2010 Elsevier Ltd.

Patients with advanced pancreatic cancer failing gemcitabine-based first-line chemotherapy are still in relatively good clinical conditions and may still require second-line chemotherapy, which is frequently administered in daily clinical practice given to without solid scientific support.A retrospective survey was carried out including 40 patients with stage III or IV gemcitabine-refractory pancreatic carcinoma. Patients received standard FOLFIRI regimen biweekly until progression or unacceptable toxicity. Response evaluation criteria in solid tumors and National Cancer Institute common toxicity criteria were employed respectively for response and toxicity assessment.Six partial responses (15%) and 14 stabilizations of disease (35%) were recorded for a tumor growth control rate of 50%. The median time to progression was 3.7 (range, 1-6.5 months), and median overall survival was 6 months (range, 2-8.2 months). A stabilization of performance status and a subjective improvement of cancer-related symptoms were recorded in 21 patients (52.5%). No correlation has been found between length of time to progression during first-line chemotherapy and length of that reported in the second-line setting or objective response. Grade 3-4 diarrhea and mucositis was observed in 15% and 10% of cases, respectively.Data presented in this article demonstrate that the second-line FOLFIRI regimen are able to induce an objective response in a relatively small fraction of patients with gemcitabine-refractory adenocarcinoma of the pancreas. The use of second-line chemotherapy should be carefully proposed to patients with good performance status or those who had a good response to first-line therapy.

Background Quality of life (QoL) has gained greater importance in the management of metastatic non-small-cell lung cancer due to the palliative nature of treatment. Docetaxel (DCT) and cisplatin (CDDP) doublet has been reported to be associated to a better QoL than the weekly vinorelbine (VNR) and CDDP regimen. Recently a newer more tolerated schedule of the VNR/CDDP regimen has been published and is widely employed in medical practice. The impact of these regimens on patients' QoL as well as symptoms control and type and grading chemo-related side-effects has been compared prospectically. Methods Patients received CDDP 75mg/m 2 plus DCT 75mg/m 2 on day 1 every weeks (arm A) or CDDP 80mg/m 2 on day 1 plus VNR 30mg/m 2 day 1 and 8 every 3 weeks (arm B). G-CSF and/or EPO were employed as needed. Health-related QoL was assessed at entry and after every cycle by the EORTC-QLQ-C30 and LC13 questionnaires, toxicity by the NCI-NCCN CTC vs 2, and intent-to-treat objective response by the Recist criteria. Results The QoL questionnaires were completed by 37 pts (88%) in the DCT/CDDP arm and 39 pts (87%) in the VNR/CDDP one. Baseline mean scores and rates at which pts failed to complete QoL assessment were similar in the two arms. Global health status of the EORTC QLQ-C30 scale and specific symptoms control (LC13 module) improved during treatment without any statistically significant difference between the two arms. Emotional functioning remained stable in both groups during treatment, whereas physical and role improved slightly. In the DCT/CDDP arm 14 pts (33%; 95%CL 24–40%) had PR, and 10 (24%) SD for a 57% TGCR. In the VNR/CDDP arm 12 pts (27%) achieved PR, 18 (41%) SD a 68% TGCR. Differences were not statistically significant. Median time-to-progression was 4.2 months in the DCT/CDDP arm and 4.5 months in the VNR/CDDP one, and median overall survival was 12.1 (range 1–26+ months) and 12.5 months (range 1–28+ months) for DCT/CDDP and VNR/CDDP arms, respectively. Febrile neutropenia rate was higher in the VNR/CDDP arm ( p =0.02) as well as G3-4 anemia ( p =0.005) and G-CSF/EPO use ( p =0.019). Conclusions Global and specific health-related QoL data similar in both treatment groups with no statistically significant difference. Efficacy measures, overall response rate, time-to-progression and overall survival were equivalent in both arms. However, severe anemia and febrile neutropenia are statistically more frequent in the VNR/CDDP arm than in the DCT/CDDP one. These data should be considered in treatment decision-making for pts with advanced non-small-cell lung cancer and for the design of future trials with chemotherapy plus biologics.

Capecitabine is an oral chemotherapeutic agent, already used in breast and colon cancer. Previous data showed encouraging results in the treatment of recurrent ovarian cancer. The aim of this study was to describe activity and toxicity of capecitabine in patients with platinum resistant or refractory ovarian cancer. Patients were eligible if they had cytologically or histologically proven epithelial ovarian cancer, refractory or resistant to prior platinum-containing chemotherapy. Capecitabine was administered at the dose of 1,250 mg/m2 twice daily on days 1–14 of a 21-day cycle for a maximum of six cycles. The primary end point of the study was activity in terms of objective response rate in according to RECIST criteria. A two-stage minimax design for phase II studies was used: at least four objective responses had to be reached among 32 evaluable patients to define the treatment active. Between March 2006 and October 2007, 36 patients were enrolled. All patients had ovarian cancer and 83.3% had previously received two or three lines of chemotherapy. Thirty-two patients were evaluable for response and included in the activity analysis. The objective response rate was 3.1% [95% exact confidence interval (CI): 0.08–16.22%], lower than the threshold required to define the treatment as active. The median progression free survival was 68 days (95% CI: 65–120). Haematological toxicity was not frequent. Nausea and fatigue were common, but never severe, and they were observed in 13 (37.1%) and 12 (34.2%) patients, respectively. Diarrhoea occurred in 11 patients (31.5%) and it was of grade 3 in 8.6% of cases. Grade 1–2 stomatitis was observed in seven patients (20%). Cardiovascular toxicity was reported in two cases, including a death for pulmonary embolism. Capecitabine is not active in platinum resistant non mucinous ovarian cancer, producing a response rate lower than that required by study design. Further trials are not warranted in these patients.

Background Doublet chemotherapy is more effective than single-agent as first line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable information instead is available on the effect of doublets in second line treatment. The aim of DISTAL-2 study was to compare two doublets containing docetaxel with single agent docetaxel as second line treatment of patients with NSCLC (ClinicalTrials.gov id.:. NCT00345059 ). Methods NSCLC patients, aged 2 on days 1, 8, 15 q 4 weeks); arm B, weekly docetaxel (30 mg/m 2 on days 1, 8, 15) plus gemcitabine (800 mg/m 2 on days 1, 8 q 4 weeks) or plus vinorelbine (20 mg/m 2 on days 1, 8 q 4 weeks) depending on which of the two had been used in first line; arm C, weekly docetaxel (as in arm B) plus capecitabine (625 mg/m 2 twice daily on days 5–18 q 4 weeks). Primary end-point was overall survival (OS). Two comparisons were planned: arm B vs. A and arm C vs. A. Overall, 375 patients had to be randomized. Response was assessed by RECIST, quality of life (QoL) by EORTC questionnaires. Results 84 patients were randomized from May 2005 to December 2006, when the trial was prematurely stopped due to the slow accrual. After 62 deaths, median OS was 40.0 weeks in arm A, 32.6 weeks in arm B ( p = 0.18 vs. A) and 39.7 weeks in arm C ( p = 0.90 vs. A). Response rate was 6.4, 16.7 and 5.3%, and median progression-free survival was 12.4, 13.1 and 11.9 weeks, for arms A, B and C, respectively. Patients in arm B had significantly more grade 3–4 haematological and non-haematological toxicity compared to arm A, and patients in arm C had significantly more grade 3–4 non-haematological toxicity compared to arm A. No relevant differences were found in QoL analysis, with the exception of significant worsening in appetite, vomiting and hemoptysis for patients in arm B. Conclusion Due to early termination, the trial does not have the planned statistical power. However, available data do not support the role of docetaxel-based combination chemotherapy as second line in advanced NSCLC.

BackgroundThis study was carried out to evaluate total basal bilirubin levels as a predictive factor for survival and toxicity in patients with advanced colorectal carcinoma treated with CTP-11-based regimens.Patients and methodsThe analysis was carried out on a data base including 287 patients affected by advanced colorectal carcinoma all treated with CPT-11 plus bolus and continuous venous infusion intravenous folinic acid and 5-fluorouracil on a biweekly schedule (FOLFIRI regimen). Patients were divided into four groups according to basal bilirubin levels as follows: 0.50 and 1.00 and 1.50mg/dl. Analysis of overall median survival and time-to-progression were correlated to performance status at entry, volume of liver metastases, and carcinoembrionary antigen.ResultsGlobal statistical analysis showed that bilirubin levels were strongly correlated with time-to-progression and overall survival in a statistically significant fashion (p

This paper is an updated review of the pre-clinical rationale and clinical results of new EGFR-targeted agents – cetuximab and panitumumab – employed in the management of advanced/ metastatic colorectal cancer. The addition of either biologic agent or last generation standard chemotherapy regimens – FOLFIRI and FOLFOX – has yielded better results as compared to those reported for chemotherapy alone. These results have been obtained without a significant increase in severe toxicity with the exception of skin side-effects.