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In stage IV colorectal cancer, bevacizumab-based maintenance therapy, complete stop therapy and continuous therapy are considered all possible approaches after first line induction chemotherapy. However, there are no clear data about which approach is preferable.All randomized phase III trials comparing bevacizumab-based maintenance therapy (MB) with complete stop therapy (ST) or with continuous therapy (CT) were considered eligible and included into the analysis. Primary endpoint was the Time to failure strategies (TFS). Secondary endpoints were Overall Survival (OS) and Progression free survival (PFS). Meta-analysis was performed in line with the PRISMA statement.1892 patients of five trials were included into the analysis. A significant improvement in TFS (HR 0.79; CI 95% 0.7-0.9 p=0.0005) and PFS (HR 0.56; CI 95% 0.44-0.71 p0.00001) were observed in favour of MB versus ST. A trend, but not statistically significant, in favour of MB versus ST was also observed for OS (HR 0.88; CI 95% 0.77-1.01, p=0.08). Comparing maintenance therapy versus continuous therapy no statistically differences were observed in the outcomes evaluated (OS 12 months OR 1.1 p=0.62, OS 24 months OR 1 p=1, OS 36 months OR 0.54 p=0.3, TFS 12 months OR 0.76 p=0.65).Our meta-analysis suggests that use of MB approach increases TFS, PFS compared to ST. Although without observing any statistically advantage, it should be highlighted that MB versus ST showed a trend in favour of MB. We observed no difference between MB and CT. MB should be considered the standard regimen in patients with stage IV colorectal cancer after first line induction therapy.

Oncological emergencies are important complication of cancer, potentially occurring in different phases of the disease. A preventive attitude, early clinical recognition, and treatment are cornerstones for patient survival and functional preservation. Therefore, oncological emergencies represent a challenge to the Emergency and Oncology Departments and in general to the hospital organization which should provide adequate diagnostic evaluation and treatment even on weekends and holidays. They are generally classified in mechanical and metabolic emergencies, but other classifications or subclassifications have been proposed to improve the nosological framework. Breast cancer, representing one of the most frequent cancers and the leading cause of cancer death among females worldwide, with an estimated 1.7 million cases and 521,900 deaths in 2012, is an important cause of oncological emergencies. Throughout this chapter, the principal oncological emergencies will be analyzed, with attention to pathophysiology, clinical features, diagnosis, and management, focusing their clinical relevance and distinctive traits in breast cancer.

To prospectively assess feasibility, side effects, and safety of a home treatment with zoledronic acid in patients with bone metastases confined to home.Forty-two patients with bone metastases (15 males and 27 females; mean age, 72 years; range, 48-86), confined to home because of functional impairment or low performance status, were enrolled into the trial. They were included in a comprehensive program of home care, and were treated with zoledronic acid, 4 mg. Primary end point of this observational trial was the safety assessment of the treatment at home; secondary end points were the clinical assessment of the time to treatment discontinuation and the definition of a pattern of patients who could benefit by a home treatment with intravenous bisphosphonates.Nineteen patients had breast cancer; 7, multiple myeloma; 5, non-small-cell lung cancer; 4, renal cancer; 4, prostate cancer; 1, thyroid cancer; 1 non-Hodgkin's lymphoma; and 1 soft tissue sarcoma. On the whole, 220 home treatments were administered in 3 years, with a median of 4 administrations per patient (range, 1-28). Median time to treatment discontinuation was 130 days. The treatment was interrupted for worsening of the performance status in 30 patients (71.4%), length of the treatment greater than 24 months in 2 patients (4.8%), hypocalcemia in 1 patient (2.4%), renal failure in 1 patient (2.4%). No difference in median time to treatment discontinuation was observed among patients with breast cancer, multiple myeloma, or other tumors in univariate analysis. Multivariate analysis showed no prognostic significance for kind of tumor, age at the time of entering the trial, gender, and number of extraosseous sites of disease. No acute major side effects were observed during the treatment, and the treatment had to be interrupted for side effects in 2 patients (4.8%). One patient had jaw osteonecrosis some months after the treatment was stopped.The home treatment with zoledronic acid seems safe. The appropriate use of biphosphonates in such a new setting needs a criterion to identify the subset of patients with bone metastases confined to home who can really benefit by this treatment.

e16519 Background: To compare efficacy and safety of E and AA in the treatment of metastatic, castration-resistant prostate cancer. Methods: Efficacy and safety of E and AA were compared using the data of the PREVAIL, AFFIRM, COU-AA-302 and COU-AA-301 trials. All the data extracted from the selected trials were reported ad Hazard Ratio (HR) or Odds Ratio (OR). Overall survival was assumed as index of efficacy, and was the primary end point of our analysis, all the side effects, grade III-IV side effects, serious side effects, side effects leading to treatment discontinuation or death were assumed as indexes of safety and were the secondary end points of our analysis. Overall survival was assessed both in the entire population and in the subgroups of patients chemotherapy-naïve or docetaxel-resistant. An alpha error of 5% was assumed as index of statistical significance. Results: The outcome of 5191 patients were reviewed. 1671 patients had been treated with E, 1339 with AA and 2181 with placebo. Comparing E vs AA no differences were observed for overall survival in the entire population (HR = 0.955, IC95% = 0.796-1.144, p = 0.616), overall survival in chemotherapy-naïve patients (HR = 0.947, IC95% = 0.723-1.24, p = 0.692), overall survival in docetaxel-resistant patients (HR = 0.961, IC95% = 0.753-1.228, p = 0.75), all side effects (OR = 0.414, IC95% = 0.054-3.196, p = 0.463), grade III-IV side effects (OR = 1.36, IC95% = 0.253-7.318, p = 0.72), serious side effects (OR = 0.742, IC95% = 0.137-4.006, p = 0.729), side effects leading to treatment discontinuation (OR = 0.743, IC95% = 0.132-4.193, p = 0.736), and side effects leading to death (OR = 0.572, IC95% = 0.089-3.657, p = 0.556). Conclusions: Although E and AA differ for pharmaceutical structure and mechanism of action, they seem to be comparable both for indication (pre- or post-docetaxel treatment in patients with metastatic, castration-resistant prostate cancer), and for efficacy or safety (in chemotherapy-naïve and docetaxel-resistant patients). It follows that compliance, patients characteristics and costs can play a role in the decision making process of clinical practice.

Background Although Indocyanine green (ICG) is used to find sentinel nodes (SN) in patients with breast cancer (BC), its role in clinical practice is still debated, and needs a definitive validation to be included in the standard approach to finding sentinel nodes in breast cancer. Materials and methods To validate the ICG methods of detecting the SN in BC we have recently concluded a prospective validation trial. Patients with clinically node-negative, invasive early BC scheduled for breast surgery and SN biopsy were included in the trial. All the patients underwent SN detection using both the standard-of-care procedure using radioisotope technetium (99mTc) and the ICG, using the Photodynamic Eye camera. A comparison of the detection rate and the diagnostic accuracy of the two methods was performed to detect the equivalency of the two approaches. Results At the end of the enrolment, 301 patients were considered eligible and included in the trial, and 589 nodes were removed. Five hundred and eighty-three nodes (99%) were identified with ICG (median 2 nodes per patient) and 452 (76.7%) were identified with 99mTc (median 2 nodes per patient). A concordance index of 98.75% (CI, 95% = 97.1%–99.5%) was detected. The dosage given ranged from 0.3 to 1.4 ml. ICG was used in all patients eligible for SN biopsy without any significant acute side effects. Conclusions The index of concordance between 99mTc and ICG seems to be extremely high, suggesting that ICG could be validated as an alternative method to 99mTc in the detection of SN in BC.

259 Background: To assess the role of chemotherapy in metastatic, hormone-naïve prostate cancer, we presents the preliminary data of a pooled analysis comparing the outcome of patients with metastatic hormone-naïve prostate cancer. Methods: A pooled analysis of the outcome of randomized clinical trials approaching the role of docetaxel in metastatic hormone-naïve prostate cancer was performed using a random effect model. The final outcome of all the patients enrolled into the trials was the primary end point of our analysis. The pooled final result was reported as pooled Hazard Ratio and 95% Confidence Interval. The between-the trials heterogeneity was assessed using the I2 test. An α-error of 5% was identified as index of statistical significance. Overall survival of the entire population enrolled into the trials was the outcome of the preliminary analysis, while no subgroup analysis was performed in this preliminary phase of a multi-steps analysis. Results: Three trials (the CHAARTED, the STAMPEDE and the GETUG-AFU 15 trial) were considered eligible and included into the analysis. A pooled Hazard Ratio of 0.76 (95% Confidence Interval of 0.59-0.98, p = 0.037) was detected for overall survival, with an I2 of 67.8. The pooled datum was obtained observed the outcome of 951 patients treated with docetaxel plus androgen blockade and 1338 with androgen blockade alone. Conclusions: Although the between-the-trials heterogeneity seems to suggest caution in the final interpretation of the results, a significant reduction of the risk of death can be obtained with docetaxel in the treatment of metastatic hormone-naïve prostate cancer. Our preliminary analysis, including all the patients with metastatic hormone-naïve prostate cancer, seems to suggest a role of docetaxel in all the patients with metastatic disease; further data are probably needed to detect its role in some different subclasses of patients (patients with high burden of the disease, fit or unfit patients, elderly patients).

Capecitabine is now-a-days rapidly replacing 5-Fluorouracil in daily clinical practice. Neurologic toxicity during a treatment with fluoropyrimidines, as 5-fluorouracil, represents a well-known side-effect, largely described in literature. Central nervous system (CNS) toxicity, mainly encephalopathy with or without seizures, occurs occasionally even when conventional doses are used. CNS toxicity incidence increases markedly when the blood-brain barrier is either overwhelmed or bypassed (Hildebrand J. Neurological complications of cancer chemotherapy. Curr Opin Oncol 2006; 18: 321—324). Peripheral nervous system (PNS) toxicity is more common because proximal and distal extremities of the peripheral nerves are not protected by a blood-brain like barrier and peripheral neuropathy remains a major limiting factor for the administration of conventional doses of several agents (Saif W, Wood TE, McGee PJ and Diasio RB. Peripheral neuropathy associated with capecitabine, Anticancer Drugs 2004;15: 767—771). Capecitabine is a prodrug of 5-fluorouracil, more easily administered by mouth; its transformation in 5-fluorouracil is performed in the liver. There are only a few reports on the toxic neurological side-effects of capecitabine. We describe in our report a rare case of toxic encephalopathy in a 82-year-old female, with a brief review of literature. In the literature reviewed, we found 12 neurologic episodes due to capecitabine lasting between a few days till some months. All clinical symptoms of the cases described in literature, obtained a complete regression with the discontinuation of capecitabine. A relation was not found with dihydropyrimidine dehydrogenase (DPD) mutation, also if pharmacologic and pharmacogenetic assessment should be done for this drug, especially in old patients. Toxic encephalopathy represents a rare event during capecitabine treatment and on the bases of the data found, is fairly managed in the clinical setting. The knowledge of the natural history of the toxic effect allows the use of the drug also in old patients.

Aim of our work was to assess the role of prognostic and predictive factors in patients to be treated with II and III line chemotherapy in metastatic colorectal cancer.All the patients with metastatic colorectal cancer treated with at least one line of chemotherapy for metastatic disease and progressed after I line chemotherapy were considered eligible and enrolled into the trial.Twenty-six out of 51 consecutive, and potentially eligible patients (51%) were considered eligible and included into the analysis. The median time to progression to I line chemotherapy was 6.7 months with no significant differences between FOLFOX and FOLFIRI (respectively 10 and 6.7 months, p = 0.71). The I line response rate was 57.7% with no significant differences between FOLFOX and FOLFIRI (respectively 46.1% vs 70%, p = 0.4). A significant improve in overall survival was observed for I line responder patients (respectively, 60 and 12 months for responder and non-responder patients, p = 0.0037), with a significant correlation with the time to progression to I line chemotherapy (p = 0.041). No statistical difference was observed for the number of lines of treatment (3 vs 2, p = 0.3), the treatment sequence (FOLFOX--FOLFIRI vs FOLFIRI--FOLFOX, p = 0.94), patient's age (p = 0.105), patient sex (p = 0.055), II line response rate (p = 0.987) and time to progression to II line chemotherapy (p = 0.151) in multivariate analysis.Our data seem to suggest a prognostic significance of I line response rate and time to progression in patients with metastatic colorectal cancer.

Lipoplatin is a liposome encapsulated form of cisplatin. phase i studies on lipoplatin have demonstrated that the compound has an excellent toxicity profile. therefore we performed a phase ii trial in heavily pre-treated patients with advanced non-small-cell lung cancer (NSClC), performance status 0-2 in which the primary endpoint was response rate and secondary endpoints were safety and overall survival.Nineteen patients, average age 64 years old, with stage iV NSClC, were treated with lipoplatin 100 mg/m(2) every two weeks, as second line chemotherapy.We observed 1 partial remission (5.2%) and 3 stable diseases (15.9%). Time to progression (ttp) was 16 weeks and median overall survival (OS) was 31 weeks (7.2 months). We observed G1-G2 toxicity during chemotherapy, mainly gastrointestinal with nausea and vomiting (4 patients), asthenia (3 patients), mucositis (2 patients) and anemia (4 patients).Our phase ii study does not support a more extensive use of lipoplatin in phase III studies. An increase of dosage and a better selection of patients are mandatory to understand the real therapeutic activity of lipoplatin.

Lipoplatin is a liposome encapsulated form of cisplatin. Phase I studies on Lipoplatin showed an excellent toxicity profile of the compound. Therefore we performed a phase II trial in heavily pre-treated patients with advanced non–small cell lung cancer (NSCLC).

Nowadays, neoadjuvant radiotherapy represents the gold standard in the treatment of locally-advanced rectal cancer. Likewise, a lot of evidences seems to suggest that preoperative chemotherapy could improve the local control of the disease, favour the downstaging of the tumor, and make possible an higher number of conservative, sphincter-sparing surgical approaches. In our paper we systematically reviewed the evidences of literature to detect both the main benefits and the limits of pre-operative chemotherapy in the treatment of locally advanced rectal cancer. Moreover, we critically reviewed both the main outcomes of preoperative chemotherapy (overall survival, disease-free interval, number of conservative, sphincter-sparing surgical approaches) and its safety (acute and chronic safety), to give clinicians an evidence-based support for their clinical practice.

e14634 Background: To assess the role of anti-EGFR agents [Cetuximab (C) or Panitumumab(P)] or Bevacizumab (B) in the treatment of RAS wild type metastatic colorectal cancer. Methods: The final res...

e15062 Background: To assess the role of Second Line Treatments (SLTs) in the treatment of metastatic, pre-treated gastric cancer. Methods: A systematic review of literature in the MEDLINE and EMBA...

e14622 Background: In stage IV colorectal cancer, Bevacizumab maintenance therapy or stop and go therapy is considered the gold standard approach after first line induction chemotherapy. However, t...

Background: Recently many authors have hypothesized that early palliative care (EPC) in patients with cancer could improve survival, quality of life or symptoms control. To confirm this datum, we have recently completed a systematic review of literature with meta-analysis of randomized clinical trials. Methods: A systematic review of literature with meta-analysis of randomized clinical trials has recently completed by our group. All the trials comparing EPC with standard approach (SA) were considered eligible and included into the pooled analysis. The quality of life improve was the primary end point of our work. The pooled analysis was performed using a random effect model, assuming an alpha error of 5% as index of statistical significance. Heterogeneity between the trials was assessed using the I2 test. The quality of the trials included into the analysis was assessed using the Jadad score. Results: Six trials were considered eligible and included into the analysis. The outcome of 1579 patients was analysed in the pooled analysis. 832 and 765 patients were respectively included in the EPC and SA arm. Heterogeneity between the trials was low, with I2 = 19.3. The Odds Ratio of the pooled analysis was 1.52 (CI95% = 1.21-1.91, p Conclusions: Our data confirm that EPC could improve quality of life of patients with advanced cancer. The datum, that is significant by a statistical point of view, is modest by a clinical point of view, with a negligible impact in the comprehensive assessment of the patient. Nevertheless, many methodological and clinical limits reduce the definitive meaning of our results, and make our conclusion controversial. Further trials, are probably needed to better define the role of EPC in the comprehensive care of cancer patients with advanced disease. Disclosure: All authors have declared no conflicts of interest.

e14557 Background: To assess the role of radiofrequency ablation (RFA) or hepatic resection (HR) in the treatment of potentially resectable liver metastases from colorectal cancer. Methods: A syste...

Numerous studies referring to conventional chemotherapy for aggressive fibromatosis with the use of doxorubicin, cyclophosphamide, vincristin, vinblastine and other drugs have been published. Imatinib mesylate is a recently developed oral anticancer agent designed to selectively inhibit tyrosine kinases implicated in oncogenesis and it seems to represent a promising opportunity (also in first line) in the treatment of patients with advanced disease not candidate to prior surgery.

7578 Background: To assess the efficacy and safety of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC on the basis of the two registrative trial...

4085 Background: Besides its large use in clinical practice, till now no definitive data exist supporting the efficacy of POC when combined with radiotherapy in improving the outcomes of LARC. Outc...

18160 Background: Lipoplatin is a liposome encapsulated form of cisplatin. Phase I studies on lipoplatin showed an excellent toxicity profile of the compound. Therefore we performed a phase II trial in pre-treated patients with advanced non-small cell lung cancer (NSCLC). Methods: Nineteen patients with stage IV NSCLC pre-treated with first line chemotherapy were enrolled in our study. Patient selection criteria included: histologically confirmed malignancy type or cytological confirmation of advanced NSCLC, at least one measurable bi-dimensional lesion outside an irradiation field, stage IV disease, a life expectancy of more than 3 months, previous chemotherapy regimens, PS 0–2, age between 18 and 75, good bone marrow function (peripheral absolute granulocyte count of > 2,000/mm3 and platelet count of 100,000/mm3) and liver function (bilirubine less or equal to 1,5 mg/dl). Patients with symptomatic brain metastases or other severe illnesses were excluded from the study. Written informed consent was required from each patient prior to inclusion. The protocol was approved by the Local Ethical Commitee. We administered lipoplatin at the dose of 100 mg/m2 every fourteen days as second line chemotherapy. Primary endpoint was response rate. Results: We enrolled 19 patients, median age 64, with stage IV NSCLC. This was an open label single-arm trial. Statistical analysis was performed with the SPSS statistical program (version 11.0). Survival curves were estimated by the Kaplan-Meier method. All of the patients completed at least 6 cycles and were evaluated for response and toxicity. After 19 patients were treated we obtained only one partial response (5.2%) and three stable diseases (15.9%) and the study was stopped. Median time to progression was four months and median survival time was 7 months. Conclusions: In this study lipoplatin as second line drug demonstrated a lower activity in comparison to other drugs used in second line treatment. Nevertheless at the light of the excellent safety profile shown we think that the possibility to increase the dose in a new phase I-II study with escalation of the dosage should be considered. No significant financial relationships to disclose.

18518 Background: Although medical oncology and palliative care are often distant dimensions in the treatment of patients with cancer, it is a common notion that an integration could improve the outcome in a comprehensive assistance to the patient. Methods: To create a Palliative Care Network (PCN) in our Department, we promote the creation of a multidisciplinary team (MT) with oncologists (2), palliativists (1), psychologists (1), social workers (2) and nurses (3) with the aim of favouring the continuity of care along all the phases of the disease. The MT gathers the competences of the oncologic and palliative care units, and is coordinated by the responsible of the supportive and palliative care unit of the district. All the patients were evaluated before entering into the project and classified in three levels with different care burden. In all the patients admitted to the PCN a palliative support is planned since the early phases of metastatic disease. The palliative care project are weekly updated by the MT. The outcomes of the PCN are evaluated every six months for activity and annually for efficacy. Results: 4589 patients have been admitted in 2003–2005 period (419 in Hospice). 2441 (53.2%), 1533 (33.4%) and 615 (13.4%) patients were classified respectively in the three increasing severity levels, and an “intensive” palliative approach was needed in 2547 (55.5%) patients. The main problems referred by the patients or their families were symptoms control, pain control, the need of psychological or social support, the need of a continuity of care along the terminal phases of the disease. Preliminary data seem to suggest a positive impact of the shared approach against the symptoms of advanced or terminal disease, and an interesting level of satisfaction by patients and caregivers seems to be confirmed in a preliminary assessment. Conclusions: The continuity of care is considered an index of the quality of care and an integrated model of palliative care should be elaborated in every oncologic district; oncologic departments seem to represent the ideal dimension where favouring an integration between medical oncology and palliative care and every effort should be made to realize this kind of integration. No significant financial relationships to disclose.

Introduction Small cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites. Case presentation We report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen. Conclusions It has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm.