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Background: Since the beginning of the covid19 pandemic, clinical and demographic data showed that cancer patients are at high risk of developing severe consequences of Sars-Cov2 disease. For this reason, vaccination is strongly recommended, especially for patients on active treatment. Nevertheless, the efficacy of the Sars-Cov2 vaccine in cancer patients is not fully investigated. Our trial aim to explore the seroconversion in a large series of vaccinated cancer patients undergoing active treatment. Here we present a subgroup analysis concerning patients affected by breast cancer. Methods: The “VAX-on” is a single-center study that enrolled 366 cancer patients who underwent oncological treatment within the last six months. The study was approved by the ethics committee and all patients had to sign specific informed consent to be enrolled. Subjects were vaccinated against Sars-Cov2 with mRNA vaccine BNT162b2 (Comirnaty) - Pfizer BioNTech. Blood samples were obtained to quantify the production of specific anti-Spike IgG antibodies at day 21 from the first dose and at 6-8 weeks after the second dose. The antibody laboratory title cut-off of 50 U.A./mL defined the seroconversion. Results are shown as Mean and Standard Deviation for continuous variable, percentage (%) for categorical ones. The Mann-Whitney test or Chi-Square test were used to compare continuous or categorical groups, respectively. Results: A total of 100 patients with breast cancer were enrolled. Clinical and demographic data are summarized in Table 1. The median age was 60.5 years and the majority had an ECOG PS of 0 (75%). Almost all were women (97%), with advanced cancer in 60% of cases. In early or advanced setting 46% patients were treated with chemotherapy while 54% were on target therapy (also including monoclonal antibody and CDK4/6 inhibitors). The mean antibody title after the first dose of mRNA Comirnaty vaccine was 2185.03±9303.26 U.A./mL (M±SD), while after the second dose the mean antibody title rise to 6492.10±10425.95 (M±SD). After the first dose 61% of patients were considered as immunized, meanwhile after the second dose 86% of patients resulted immunized (defined as an antibody title >50 U.A./mL). In the 9 patients in treatment with steroids (prednisone > 10mg/die or equivalent), there was a trend to a decreased antibody development compared to patients without chronic use of steroids (p 0.06 and 0.05 after the first and second dose, respectively). Of interest, patients using G-CSF (12%) had a significant reduction in the production of Sars-Cov2 antibody after vaccination compared to patients who did not use them (p 0.02 and Table 1.Parameters *Gender (F) (%)97 (97.00)Age (yrs)60.55±11.94Advanced Stage (Yes) (%)60 (60.00)ECOGPS (%)075 (75.00)121 (21.00)24 (4.00)Setting (%)Other Therapy60 (60.00)Adjuvant & Neoadjuvant40 (40.00)Therapy (%)Other46 (46.00)Target54 (54.00)Last cycle 10 mg)/> 7 days9 (9.00)FANS last 7 days (Yes) (%)15 (15.00)G-CSF last 21 days (Yes) (%)12 (12.00)Previous Allergies (Yes) (%)19 (19.00)Antibody Title 1st Dose2185.03±9303.26Antibody Level 1st Dose (>50) (%)61 (62.89)Antibody Title 2nd Dose6492.10±10425.95Antibody Level 2nd Dose (>50) (%)86 (92.47) Citation Format: Agnese Fabbri, Eleonora Marrucci, Fabrizio Nelli, Marco Mazzotta, Angelo Onorato, Primi Francesca, Mario Giovanni Chilelli, Antonella Virtuoso, Carlo Signorelli, Julio R Giron Berrios, Marta Schirripa, Rossella Donghia, Enzo Maria Ruggeri. Evaluation of the effects of anticancer treatments in cancer patients undergoing SARS-COV2 vaccination (VAX-on study: Breast cancer subgroup analysis) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-11-02.

Background Numerous research studies have looked into how the primary tumor location (PTL) affects patients' prognosis for colorectal cancer (CRC). Our research aimed to investigate the prognostic effects of PTL in patients with synchronous (SM) and metachronous (MM) colorectal cancer liver metastases (CRCLM). Material and methods From 2016 to 2021, we looked back at the records of patients at our institute who were affected by CRCLM. Results 109 patients were included, of whom 21.1% received CRCLM resection (R0=73.9%), with 57.7% having left-sided colon cancer (LCC) and 42.2% having right-sided colon cancer (RCC). SM predominated (69.7%). The median duration of follow-up was 21,3 months (95%CI=15,4-25,2). ≥5 hepatic metastases prevailed in the SM group (N=61; 83.5%). 21% of all patients underwent CRCLM resection (R0=78.2%). We observed a double rate of patients unresponsive to standard systemic antineoplastic treatments in the SM group (35.8% vs. 17.9% of the MM group) (p=0.27). We found a significantly longer median overall survival (OS) in patients with MM-LCC compared with the other groups (27.7 months; HR=0.3797; 95%CI=0.19-0.74; p=0.0205). The median OS, regardless of PTL, was higher in the MM group (16,5 months vs. 16,1 months; HR=0,29; 95%CI=0,13-0,67; p=0.0038) as well as progression-free survival (PFS) (11 months vs. 10,2 months; HR=0,61; 95%CI=0,33-1,12; p=0.11). Finally, in patients undergoing liver surgery, a noteworthy median OS was shown to be significantly in favor of patients with metachronous liver metastases from the primary left tumor (37.0 months; HR=0.47; 95%CI=0.11-1.96; p=0.0041). Conclusions Our real-life study demonstrated that patients with LCC, particularly MM-LCC, have the highest survival and that the timing of CRCLM should be a prognostic factor.

Background The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors (ICIs) are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. Methods Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of ICI treatment before vaccination for an advanced solid malignancy were eligible. Results The current analysis included 56 patients with metastatic disease (median age: 66 years; 71% male), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 3424 AU/mL allowed a dichotomization of recipients into low-responders (Low-R

The adaptive immune response following COVID-19 vaccination is essential for humoral immunogenicity and clinical protection against symptomatic infections. We present the results of circulating lymphocyte profiling and their correlation with antibody response in cancer patients tested serologically six months after receiving a two-dose schedule of mRNA-BNT162b2 vaccine.Absolute counts of lymphocyte subsets were determined using peripheral blood immunophenotyping. We collected samples for flow cytometry analysis alongside quantitative detection of IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S1). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response.311 patients were evaluable for lymphocyte profiling and serologic testing. A preliminary multivariate analysis revealed that cytotoxic chemotherapy was the most consistent factor associated with lower counts of all lymphocyte subpopulations. T helper and B cells were found to be useful in predicting the occurrence of a positive seroconversion response using ROC curve analysis. A significant positive linear correlation was shown when anti-RBD-S1 IgG titers were compared to these lymphocyte subset counts. Univariate analysis indicated that antibody titers and seroconversion rates were significantly improved in the high-level T and B cell subgroups. Multivariate analysis confirmed these significant interactions, as well as the negative predictive value of immunosuppressive corticosteroid therapy.These findings suggest that simple and widely available peripheral counts of T helper and B cells correlate with humoral response to mRNA-BNT162b2 vaccine in actively treated cancer patients. Upon validation, our results could provide additional insights into the predictive assessment of vaccination efficacy.

We evaluated immune cell frequencies in peripheral blood samples of 41 NSCLC patients before and after second-line therapy with anti-PD-1/PD-L1 agents. Changes in lymphocyte subsets and their correlation with clinical response, progression-free survival (PFS), and overall survival (OS) were analyzed. We observed an increase in median values of all lymphocyte subsets, being significant only for NK cells. A correlation was retrieved between higher post-treatment NK cell level and clinical benefit. On multivariate analysis, PD-L1 tumor proportion score ≥1% and higher post-treatment NK cell counts were predictive of longer PFS and OS. Co-presence of these factors was characterized by longer survival.

Small cell lung cancer (SCLC) is an aggressive disease, difficult to treat. There have been no significant therapeutic advances over platinum and etoposide chemotherapy in the last 20 years until the introduction of immunotherapy. In 2020 atezolizumab, an immune checkpoint inhibitor against PD-L1 was approved in Italy in combination with carboplatin and etoposide for the first-line treatment of patients with extensive stage disease (ES-SCLC), becoming the new standard treatment. On May 20, 2021, a virtual meeting, directed by profs. Federico Cappuzzo and Emilio Bria, was held in which 14 clinicians from different oncology centers in Lazio, Umbria and Sardinia discussed the issues of ES-SCLC patients treatment, after the advent of immunotherapy. The aim of the meeting was to share their clinical experience and to provide a series of practical indications that can support clinicians in the management of ES-SCLC patients in first-line with chemo-immunotherapy.

Pemetrexed maintenance significantly improved progression-free survival (PFS) and overall survival (OS) in advanced nonsquamous non-small-cell lung cancer (NSCLC) patients not progressing after induction chemotherapy.This study is aimed at examine the association of various clinical factor and survival in a real-world cohort analysis.One hundred ninety-four patients were included and classified as "PM" cohort ("Pemetrexed Maintenance", including patients given with pemetrexed maintenance after induction chemotherapy, n=112), and "noPM" cohort ("no Pemetrexed Maintenance" including those discontinuing pemetrexed, n=82).The median PFS was 8.8 and 5.4 months in the PM and noPM cohorts, respectively (p=0.001). The median OS was 19.6 months in the "PM" cohort and 13.2 months in the "noPM" cohort (p0.02). In the multivariate analysis, ECOG Performance Status (PS) 0 and maintenance therapy were independently associated with improved PFS and OS. A longer median PFS was reported in patients given ≥5 cycles of pemetrexed maintenance (p0.01).These results further confirm the survival benefit of pemetrexed maintenance in a real-word population. All eligible advanced NSCLC patients should be strongly considered for at least 5 of pemetrexed maintenance.

Lung cancer is a disease extremely heterogeneous in the molecular aspect and knowing the mutational profile of patients is essential in order to initiate the most appropriate treatment. In 2018, alectinib was approved in Italy for the first-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC), becoming a new therapeutic option for this patient group which constitutes approximately 3-7% of patients with NSCLC. On October 26th a virtual meeting was held in which 10 clinicians from various oncology centers in Lazio took part on the management of therapy of patients with Alk translocation, directed by Dr. Maria Rita Migliorino. The aim of the meeting was to share their clinical experience and to provide a series of practical that can help clinicians during treatment with target therapies in ALK-positive NSCLC.

Preliminary analysis from the Vax-On study did not find a correlation between cancer treatment type and antibody response to COVID-19 vaccination. We carried out a secondary subgroup analysis to verify the effects of comprehensive cancer treatment classification on vaccine immunogenicity.The Vax-On study prospectively enrolled patients who started a two-dose messenger RNA-BNT162b2 vaccine schedule from 9 March 2021 to 12 April 2021 (timepoint-1). Those on active treatment within the previous 28 days accounted for the exposed cases. Patients who had discontinued such treatment by at least 28 days or received intravesical therapy represented the control cases. Quantification of immunoglobulin G (IgG) antibodies against the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein was carried out before the second dose (timepoint-2) and 8 weeks thereafter (timepoint-3). Seroconversion response was defined at ≥50 arbitrary units/ml IgG titer. Classification of antineoplastic agents was based on their pharmacodynamic properties.Three hundred and sixty-six patients were enrolled (86 and 260 as control and exposed cases, respectively). Univariate analysis revealed a significantly lower IgG titer after both doses of vaccine in subgroups treated with tyrosine kinase inhibitors (TKIs), multiple cytotoxic agents, alkylating agents, and topoisomerase inhibitors. At timepoint-3, seroconversion response was significantly impaired in the topoisomerase inhibitors and mechanistic target of rapamycin (mTOR) inhibitors subgroups. After multivariate testing, treatment with alkylating agents and TKIs was significantly associated with a reduced change in IgG titer at timepoint-2. Treatment with mTOR inhibitors resulted in a similar interaction at each timepoint. Cyclin-dependent kinase 4/6 inhibitor treatment was independently correlated with an incremental variation in IgG titer at timepoint-3. Specific subgroups (TKIs, antimetabolites, alkylating agents, and multiple-agent chemotherapy) predicted lack of seroconversion at timepoint-2, but their effect was not retained at timepoint-3. Eastern Cooperative Oncology Group performance status 2, immunosuppressive corticosteroid dosing, and granulocyte colony-stimulating factor use were independently linked to lower IgG titer after either dose of vaccine.Drugs interfering with DNA synthesis, multiple-agent cytotoxic chemotherapy, TKIs, mTOR and cyclin-dependent kinase 4/6 inhibitors differentially modulate humoral response to messenger RNA-BNT162b2 vaccine.

With the advent of immunotherapy, the life expectancy of patients with advanced non-small cell lung cancer (NSCLC) is dramatically improved. As described in the most recent clinical trials, the addition of immunotherapy to the available therapeutic strategies, restoring an efficient immune response against neoplasms and establishing an immunological memory, is able to improve both patient's survival and quality of life. This paved the way for new therapeutic algorithms, new combination strategies, as well as the possible use of adoptive immunotherapy. Although the use of immunotherapy is now widely employed in the different phases of lung cancer, we have not yet fully understood what are both the actual mechanisms of action and resistance to checkpoint inhibitors, predictive factors of response, immuno-related response criteria, and interferences between immunotherapy and tumor microenvironment, as well as angiogenesis and its interactions with conventional therapies, such as chemotherapy. The objective of this critical review is to frame the relevant results obtained with immunotherapy in NSCLC, providing insights to help overcome decision-making for a better therapeutic choice. In addition, returning to the study of pulmonary physiology and preclinical data, we will address the new issues on the heterogeneity of response to anti-PD1/anti-PD-L1, including their combinations, in NSCLC. Moreover, to date, we are facing with patterns of response different from those previously seen with cytotoxic or target therapies. Indeed, different radiological evaluation criteria have been proposed to evaluate response to immunotherapy and further efforts are needed to identify a unique system of evaluation and other than PDL1 biomarkers, to integrate radiology in the assessment of response.

BACKGROUND/AIM Recent data highlighted that location of metastatic colorectal cancer (mCRC) may have a prognostic impact and also a predictive value of the outcomes of first-line therapy. MATERIALS AND METHODS The records of mCRC patients who underwent first-line therapy from 2011 to April 2018 at our Institute were retrospectively reviewed. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) according to the primary tumor location were investigated. RESULTS Overall, 130 patients were eligible. Two-year OS was 82.9% in left-sided colon cancers (LCC) and 67.5% in right-sided (RCC) (p=0.32). One-year mPFS was statistically longer in LCC (46.8% vs. 24.2%, p=0.0005). mPFS was longer in LCC treated with anti-VEGF vs. anti-EGFR (p=0.06). ORR was 51.1% in LCC, 25% in RCC (p=0.008). Overall, 11 complete responses all in LCC were observed (p=0.03). CONCLUSION Tumor location has a prognostic impact and might influence the outcomes of mCRC patients.

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.

Background The impact of previous cumulative exposure to CS before treatment start is unknown, while its use for the treatment of immune-related adverse events during PD-(L)1 therapy does not seem to reduce efficacy. We used real-world data to evaluate the effect of CS immunosuppressive dose (cumulative dose of > 700 mg of prednisone equivalent) or CS delivery modality (prolonged, daily dose >10 mg of prednisone equivalent lasting >5 days, or pulsed, duration ≤5 days) over 3 months before treatment start. Methods Patients with advanced NSCLC treated at our Institution with single agent PD-(L)1 blockade after failure of platinum-based chemotherapy and on CS treatment in the previous 3 months were included. Clinical and pharmacy records were reviewed to identify CS dose and duration. According to the label, patients must not have received CS > 10 mg prednisone or equivalent over 10 days before start of anti-PD-(L)1 therapy and had PS ≤ 1. Patients must also have received >2 cycles of PD-(L)1 blockade to be eligible for efficacy analysis. Results We identified 62 patients fulfilling our inclusion criteria, 28 (45%) and 36 (58%) of them received a CS immunosuppressive dose and pulsed CS, respectively, 8 (13%) had brain metastases, and 20 (32%) had squamous histology. As of the general population, 36 (58%) patients achieved a durable clinical benefit (DCB, partial response or stable disease >6 months). The median PFS was 4.3 months, and the 1-year survival rate was 39%. CS immunosuppressive dose was not associated with decreased DCB (44% vs 55%; p-value 0.9), nor with shorter median PFS (3.7 vs 4.4 months; HR 1.2; p-value 0.2), nor with lower 1-year survival rate (31% vs 43%; p-value 0.6). CS prolonged exposure was significantly associated with either decreased DCB (30% vs 69%; p-value 0.01) and shorter median PFS (2.7 vs 4.5 months; HR 1.8; p-value 0.05), but not with lower 1-year survival rate (29% vs 41%; p-value 0.06). Conclusions Prolonged exposure to > 10 mg of prednisone equivalent through pretreatment 3 months was associated with poorer outcome in patients with advanced NSCLC treated with second-line PD-(L)1 blockade. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

We retrospectively evaluated the efficacy of first-line epirubicin and docetaxel in patients with metastatic, hormonal receptor (HR)-positive, and human epidermal growth factor receptor-2-negative breast cancer. A subgroup analysis evaluated the predictive value of immunohistochemistry-defined luminal subtype.We included patients with at least one visceral and measurable site of metastatic disease. Patients were grouped as luminal A (HR(+) and Ki6713%) or luminal B (HR(+) and Ki6713%).Forty-four patients were entered and prognostic variables were similar between the subgroups. Luminal B patients achieved higher objective response rate than luminal A (69% versus 19%; P = 0.001), longer time to progression (12.2 months versus 8.6 months; P = 0.039), and longer overall survival (24.6 months versus 19.5 months; P = 0.041). The multivariate analysis confirmed the predictive value of luminal B subtype for longer time to progression.Identification by Ki67 labelling index of human epidermal growth factor receptor-2-negative luminal A could predict a substantial benefit from systemic chemotherapy. Endocrine therapy would be the most appropriate therapy for luminal A tumours.

This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan.Seventy patients received a regimen composed of weekly irinotecan 125 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest. The predictive value of adverse events (AEs) attributable to cetuximab (rash) and major toxicities attributable to irinotecan (gastrointestinal [GI] and hematologic) were observed after the first cycle of treatment and, therefore, correlated to activity and efficacy of cetuximab and weekly irinotecan.Sixty-six of 70 patients receivedor= 1 cycle of chemotherapy and were therefore evaluable for response. Overall, toxicity observed was generally mild and manageable. According to an intent-to-treat analysis, a partial response was exhibited in 15.7% of patients, with a median progression-free survival (PFS) and median overall survival time of 4 months and 9 months, respectively. As expected, PFS (P = .01) and median survival (P = .04) correlated strongly with the presence and severity of the rash. Surprisingly, the presence of at least moderate hematologic and GI toxicity was associated with improved PFS (P = .03).Our data suggest that irinotecan-induced AEs might predict a better outcome in advanced CRC. This finding would identify a different subset of patients-those likely to benefit from a renewed sensitivity to irinotecan induced by cetuximab.

337 Background: Abiraterone acetate (AA) is a potent, selective androgen (CYP17) biosynthesis inhibitor, which showed to improve overall survival in mCRPC pts progressing after docetaxel. Few data are available concerning the clinical outcome of AA treatment in mCRPC in terms of the duration of prior androgen deprivation therapy (ADT). In this retrospective analysis we assessed the PFS and OS in patients affected with mCRPC according to the duration of ADT. Methods: We retrospectively reviewed the clinical data of pts affected by mCRCP progressive after chemotherapy who received AA (1000 mg/d) plus prednisone (5 mg/twice daily). A total of 189 pts were included in the analysis, 71 received AA with ADT duration 50% was observed in 50 % of pts in both groups. AA was well tolerated and no relevant toxicity were observed Conclusions: This retrospective analysis showed a benefit in terms of PFS and OS in group B patients, our finding might be related to the best prognostic factors of patients in group B (less symptomatic).

Several improvements in the treatment of advanced transitional cell malignancies have been provided by clinical trials in the past 10 years. Nonetheless, there are conflicting results regarding the effect of perioperative chemotherapy of muscle-invasive disease and new cytotoxic agents in the metastatic setting. The authors will discuss the results of major clinical trials and examine developing targeted-oriented treatment strategies.

BACKGROUND The treatment of muscle-invasive bladder carcinoma should include both the eradication of local disease and the elimination of potential micrometastases. To date, the ‘gold standard’ treatment for muscle invasive bladder carcinoma has been recognized to be radical cystectomy. Adjuvant chemotherapy (AC) has the advantage of being administered to patients with known prognostic factors of recurrence. A pooled analysis was used to verify whether AC is able to increase the disease-free survival (DFS) and overall survival (OS) of patients with muscle-invasive bladder carcinoma who had undergone radical cystectomy. METHODS All published randomized Phase III studies were considered eligible and a literature-based pooled analysis was accomplished. DFS and OS were the endpoints. Event-based relative risk ratio (RR) and 95% confidence intervals (95% CI) were derived. Combined effect estimation was computed with a fixed- and a random-effect model. A heterogeneity test was applied as well. RESULTS Five trials were collected. All were evaluable for OS (350 patients) and four of these also were evaluable for DFS (273 patients). A significant benefit from AC was noted both in OS (RR, 0.74; 95% CI, 0.62–0.88 [P = 0.001]) and DFS (RR, 0.65; CI 0.54–0.78, [P < 0.001]). No significant heterogeneity was found. CONCLUSIONS Although the results of the analysis favor the use of AC, larger studies are needed to identify the role of AC in the treatment of muscle-invasive bladder carcinoma. Ongoing trials (European Organization for Research and Treatment of Cancer [EORTC]/Southwest Oncology Group [SWOG] and the Italian Multicentric Study) can help to better identify patients who can benefit from this approach. Cancer 2006. © 2006 American Cancer Society.

The aim of the study was to describe in detail the impact of aging and comorbidities on safety and efficacy of gemcitabine-cisplatin in the subset of elderly with advanced NSCLC. We report the results of our study which enrolled patients aged over 65 years or older. This study included 46 patients consecutively admitted to our Department. Treatment consisted of gemcitabine 1250 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 2, of a 21-day cycle. The Charlson score method was chosen to evaluate the conditions of comorbidity. All patients were evaluable for toxicity and 44 for activity. A total of 128 courses were administered, with a median of 3 courses per patient and a dose-intensity of 93% and 88% for gemcitabine and cisplatin, respectively. Grade 3-4 neutropenia (22% of patients) and grade 3 asthenia (4.5%), emesis (4.5%) and nephrotoxicity (4.5%) were the most severe adverse events. Univariate analysis of toxicity did not show any significant difference among all groups. The overall response rate was 45.6% (95% CI, 31.3-60). At a median follow up of 13 months, the median and progression-free survival were 15 and 8 months, respectively. The multivariate analysis resulted in objective response and disease control being predictive of longer survival. The combination of gemcitabine and cisplatin appears to be an effective and tolerated regimen for elderly patients with advanced NSCLC, regardless of aging and condition of comorbidities. Prospective randomized trials based on specific geriatric assessment are required to obtain compelling information for the optimal management of elderly patients with advanced NSCLC.

BACKGROUND The objective of this study was to evaluate the activity and toxicity of combined cisplatin, etoposide, and gemcitabine (PEG) and combined cisplatin plus gemcitabine (PG) in previously untreated patients with extensive-stage and poor-prognosis limited-stage small-cell lung carcinoma. METHODS One hundred forty patients (70 patients in two arms) were randomized to receive either cisplatin 70 mg/m2 on Day 1, etoposide 50 mg/m2 on Days 1–3, and gemcitabine 1000 mg/m2 on Days 1 and 8 or cisplatin 70 mg/m2 on Day 1 plus gemcitabine 1250 mg/m2 on Days 1 and 8. Both regimens were recycled every 21 days. RESULTS In total, 626 cycles were delivered (303 cycles of PEG and 323 cycles of PG), with a median of 4 cycles per patient in both arms. The objective response rate was 63% (95% confidence interval [95%CI], 49–71%) for PEG and 57% (95%CI, 43–67%) for PG, with the suggestion of a higher complete response rate in the PEG arm (18.6% and 4.3%, respectively). A similar time to disease progression (6 months in the PEG arm and 7 months in the PG arm) and a similar median survival (9.5 months in the PEG arm and 10 months in the PG arm) were observed in both arms. The PEG regimen was associated with more severe hematologic toxicity in terms of neutropenia, febrile neutropenia, and a higher rate of treatment delays and dose reductions, whereas nonhematologic toxicities did not differ between the two arms. CONCLUSIONS According to the results of this Phase II randomized trial, the PEG regimen produced a higher complete response rate but more toxicity compared with the PG regimen in patients with extensive-stage or poor-prognosis, limited-stage small cell lung carcinoma. Cancer 2005. © 2005 American Cancer Society.

BACKGROUND The objective of the current study was to define the activity and tolerability, as well as the influence on resectability, of the combination of gemcitabine, paclitaxel, and cisplatin (GTP) as induction chemotherapy for patients with Stage IIIA(N2) nonsmall cell lung carcinoma (NSCLC). METHODS Forty-nine chemotherapy-naive patients (median age, 61 years; World Health Organization performance status, 0–1) with biopsy-proven Stage IIIA(N2) disease received 1000 mg/m2 gemcitabine, 125 mg/m2 paclitaxel, and 50 mg/m2 cisplatin on Days 1 and 8 of every 3 weeks until reevaluation for surgery or definitive radiotherapy. RESULTS Grade 3–4 neutropenia was the most common hematologic toxicity, occurring in 32.7% of patients; however, only 1 case of febrile neutropenia was reported. Grade 3–4 thrombocytopenia occurred in 12.2% of patients but was not associated with bleeding. Severe nonhematologic toxicities were uncommon; the only Grade 4 nonhematologic toxicity was diarrhea, which occurred in 4% of patients. One patient died after the first course of therapy, but this event was found to be unrelated to treatment. Thirty-six patients (73.5%) achieved an objective response, and an additional 4 patients had stable disease with clearance of mediastinal lymph nodes. Overall, 29 patients underwent thoracotomy and 27 (55%) underwent complete resection. Mediastinal nodes were free of tumor in 35% of all cases, and 8 pathologic complete responses (16%) were reported. Median survival was 23 months, with a 1-year survival rate of 85%. CONCLUSIONS GTP is highly active as an induction chemotherapy regimen for Stage IIIA(N2) NSCLC and yields good toxicity results. The use of GTP in combination with radiotherapy and new biologic drugs should be explored. Cancer 2003. © 2003 American Cancer Society. DOI 10.1002/cncr.11662

BACKGROUND The objective of this trial was to evaluate the activity and safety of one of the newer platinum-based doublets as a neoadjuvant regimen in patients with unresectable Stage IIIA-bulky N2 and Stage IIIB nonsmall cell lung carcinoma (NSCLC). METHODS From June 1996 to April 2000, 129 consecutive patients with locally advanced NSCLC were treated with gemcitabine, 1000 mg/m2 on Days 1 and 8 and cisplatin, 70 mg/m2 on Day 2 (GC) of a 21-day treatment cycle, for 4 cycles, as part of a combined-modality approach. RESULTS After induction chemotherapy, 80 patients (62%; 95% confidence interval, 53.6–70.4%) achieved a partial response, 43 patients (33%) had stable disease, and 6 patients (5%) had disease progression during chemotherapy. Forty patients (31%), were considered resectable and underwent thoracotomy. Complete resectability was obtained in 38 patients (29%), with 2% of patients achieving a pathologic complete response. After surgery, 9 patients with Mountain Classification Stage IIIA NSCLC and 9 patients with Stage IIIB NSCLC received definitive adjuvant radiotherapy. Forty-six of 52 patients with Stage IIIB disease and 24 of 37 patients with Stage IIIA disease who were not considered suitable for surgery received definitive radiotherapy. The median time to disease progression was 11.4 months, the median survival was 19.4 months (range, 1.2–55.2 + months), and the 1-year survival rate was 74%. The lungs (33%) and the brain (21%) were the main sites of recurrence. Major toxicity was comprised of Grade 3–4 thrombocytopenia, which occurred in 34 patients (27%). CONCLUSIONS GC administered according to a 3-week schedule was a highly active and safe regimen in patients with primary, unresectable, locally advanced NSCLC. Cancer 2003;98:128–34. © 2003 American Cancer Society. DOI 10.1002/cncr.11460

Monoclonal antibodies bevacizumab and cetuximab both improve overall survival (OS), progression free survival (PFS) and overall response rate (ORR) when combined with irinotecan-containing regimens. The optimal sequence of these monoclonal antibodies in combination with chemotherapy is controversial. This study analysed the efficacy of cetuximab plus Folfiri after progression with the same regimen plus bevacizumab in patients with metastatic colorectal cancer (mCRC). Patients are eligible if progressive disease (PD) after Folfiri-bevacizumab; ECOG PS 0–1. Primary endpoint is the disease control rate (DCR:ORR plus stable disease > 6 months); secondary endpoints: ORR, PFS, duration of response, OS and toxicity. ORR and DCR were reported with their confidence interval at 95%. Kaplan-Meier method was used for PFS and OS evaluation. Results: 54 patients were enrolled to receive Folfiri-cetuximab after PD to Folfiri-bevacizumab treatment. Median age was 65 (43–80), M/F 31/23, ECOG PS 0/1 was 36/ 18, WT Kras 33(61%). The DCR was 64.8% (CI 95% 52.1-77.5). Among the group of patients with stable or progressive disease at first line treatment, 13.3% of them obtained a response at second line. For second line treatment median duration of response was 6 months and clinical benefit 7 months. The ORR was 22.2% (CI 95% 11.1-33.3). The median progression-free survival was 7 months (CI 95% 6–8). The median overall survival for second line treatment was 14 months (CI 95% 11–17). No grade 4 toxicity was observed. Data suggest that this sequential combination therapy is active and well tolerated. At disease progression to first line chemotherapy treatment the maintenance of the same chemotherapy regimen and the change of the monoclonal antibody showed efficacy in response and survival in patients with mCRC.

The addition of bevacizumab to standard chemotherapy has improved progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) in both first- and second line treatment, but the role of maintenance bevacizumab remains controversial. The association of various clinical factor and survival was examined in this retrospective cohort analysis. The clinical data from 220 previously untreated patients with mCRC, not progressive at the end of standard chemotherapy plus bevacizumab, were collected and analyzed. Patients were classified into two subgroups: those given with maintenance bevacizumab: “maintenance bevacizumab cohort (n = 118; MB)”, and those discontinuing bevacizumab as a result of physician’s or patient’s decision: “no maintenance bevacizumab cohort (n = 102; noMB)”. The baseline factors were well balanced between the study subgroups. Median PFS and OS for the general population was 10 months (range 7–15) and 22.5 months (range 18–26), respectively. Median PFS was 13 and 8 months in the BM and noBM cohorts, respectively (p < 0.0001). In the multivariate analysis, maintenance therapy resulted independently associated with improved PFS (HR 1.73; p < 0.001), but only objective response (OR) after first-line chemotherapy was associated with improved OS. Maintenance chemotherapy cannot be considered a standard of care after induction chemotherapy for mCRC, because the optimal balance between efficacy and safety of maintenance therapy remains a significant challenge. The results of our retrospective study suggest that maintenance therapy with bevacizumab is a safe and valuable option, particularly in those patients achieving an objective response after first-line chemotherapy.

We evaluated the efficacy of gemcitabine and carboplatin for patients affected by pretreated metastatic breast cancer. A subgroup analysis was performed to evaluate the predictive value of immunohistochemically defined breast cancer subtypes.We included human epidermal growth factor 2 (HER-2) negative metastatic breast cancer resistant to previous anthracycline-based and taxane-based chemotherapy, and HER-2 positive metastatic breast cancer with at least two progressions of disease during protracted trastuzumab-based therapy. Treatment consisted of gemcitabine (1000 mg/m(2) intravenous (iv) on days 1 and 8) and carboplatin (area under the curve 5 iv on day 1) applied every 3 weeks.Forty-two patients were registered. Disease control was 58%, with a median time-to-progression (TTP) of 7 months (range 1-12) and a median overall survival of 10.5 months (range 1-34). Patients were grouped as triple negative (ER and PR negative, HER-2 negative), HER-2 (HER-2 positive, ER and PR negative), luminal B (ER and/or PR positive and either HER-2 positive and/or high Ki67), and luminal A (ER and/or PR positive and HER-2 negative and low Ki67). For luminal A patients, disease control was lower (luminal A 34 vs. others 67%; P = 0.02), TTP was shorter (luminal A 2.4 months vs. others 6.3 months, P = 0.015), and overall survival was shorter (luminal A 7.5 months vs. others 11.7 months, P = 0.034) than for other subtypes.Gemcitabine and carboplatin are effective for pretreated patients with metastatic breast cancer. Luminal A subtype seems to fare poorly compared with other subtypes. Specific difference in gene expression might account for the different outcome.

Brain metastases are the most common intracranial tumors, occurring in 15–40% of cancer patients with an estimated incidence of 170,000 new cases a year in the United States (Davey, 2002). Lung cancer is the most common primary source of metastases to the central nervous system (CNS), causing brain metastases in 10–64% of patients. Non-small-cell lung cancer (NSCLC) represents 85% of lung cancers, and brain metastases are a frequent finding with an overall incidence of 20–40% of cases during the course of the disease (Langer and Mehta, 2005). The incidence of brain metastases in NSCLC has increased in recent years, probably owing to the longer survival of patients as a result of aggressive treatment of primary tumor and of the improvements achieved in neuroimaging (e.g., magnetic resonance imaging techniques and systematic CNS staging). However, a recent epidemiological study did not confirm this increased incidence (Schouten et al., 2002). This discrepancy probably depends on differences in the type of study undertaken (autoptically vs. clinical). A clear relation is known between stage of disease and incidence of brain metastases, and it is interesting to note that 25–30% of new NSCLC cases present with synchronous brain metastases (Sorensen et al., 1988).

Aims and Background The purpose of this pilot study was to determine the safety and feasibility of a complete integrated approach, including induction chemotherapy with carboplatin/paclitaxel followed by accelerated hyperfractionated radiotherapy with concurrent chemotherapy, and then by consolidation chemotherapy for locally advanced stage III non-small cell lung carcinoma. Methods Systemic doses of carboplatin AUC 6 and paclitaxel (200 mg/m2), 3 weeks out of 4, were planned as induction and consolidation chemotherapy. Weekly carboplatin AUC of 2 plus paclitaxel (50 mg/m2) were given during thoracic radiotherapy. Results Eighteen patients were enrolled: 10 were evaluated at the end of chemoradiation and 8 received consolidation chemotherapy. On an intent-to-treat basis, 55% of patients achieved a response after induction therapy, whereas chemoradiation and consolidation therapy increased the response rate by 33% and 16%, respectively. No patient experienced grade >3 acute hematologic toxicity during systemic-dose chemotherapy. With the exception of one episode of a severe cardiac adverse event, non-hematologic toxicity was similarly tolerable. Severe acute adverse events observed during concurrent chemoradiation were mainly represented by esophagitis, resulting in interruption of the radiotherapy in 25% of patients. More notably, only one patient experienced serious non-hematologic late toxicity. Conclusions Although the present approach seemed feasible, our data did not support any possible advantage in favor of this three-phase integrated treatment, and therefore the design will not be investigated in a subsequent phase II study.

BACKGROUND. For patients with stage IV nonsmall cell lung cancer (NSCLC) who present with brain metastasis (BMs), standard platinum-based chemotherapy regimens have challenged the role of up-front whole-brain radiotherapy (WBRT). METHODS. In this survey, the authors analyzed the decision tree by which 6 oncologic centers guided the pattern of care in an unselected population of patients with NSCLC who presented with BMs at first diagnosis. The impact of front-line, platinum-based chemotherapy also was evaluated. Individual data were reviewed from 156 eligible patients who were referred to participating centers. RESULTS. Up-front treatment included chemotherapy in 110 patients and WBRT followed by chemotherapy in 46 patients. The selection of first treatment was guided based mainly on the presence of by BM symptoms, with chemotherapy selected for 24% of patients in the chemotherapy cohort and for 76% of patients in the chemotherapy and WBRT cohort. Regardless of treatment, the brain response was 29% (27% and 35% for the chemotherapy and WBRT cohorts, respectively; P value not significant). For the entire population, the overall response rate was 37%, progression-free survival was 6 months, and the median survival was 11 months. At multivariate analysis, significant predictors for survival were: brain response (hazard ratio [HR], 2.59; P = .0001), modified Radiation Therapy Oncology Group class (HR, 0.87; P = .003), and Eastern Cooperative Oncology Group performance status (HR, 1.49; P = .04). CONCLUSIONS. For patients with NSCLC who present with BMs at first diagnosis, the results of the current survey confirmed that the expected benefit of platinum-based chemotherapy may be translated into clinical practice and that selected subsets of patients who receive frontline chemotherapy (ie, patients in whom BM symptoms are absent or are controlled by supportive therapy) may be spared from WBRT. Further prospective studies evaluating different approaches and interventions are warranted. Cancer 2007. © 2006 American Cancer Society.

Summary Background To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. Patients and Methods Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m2, paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m2). Toxicity and response of radio-chemotherapy treatment have been assessed. Results Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. Conclusion Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.

The objective of this study was to evaluate the activity and toxicity of combined cisplatin, etoposide, and gemcitabine (PEG) and combined cisplatin plus gemcitabine (PG) in previously untreated patients with extensive-stage and poor-prognosis limited-stage small-cell lung carcinoma.One hundred forty patients (70 patients in two arms) were randomized to receive either cisplatin 70 mg/m2 on Day 1, etoposide 50 mg/m2 on Days 1-3, and gemcitabine 1000 mg/m2 on Days 1 and 8 or cisplatin 70 mg/m2 on Day 1 plus gemcitabine 1250 mg/m2 on Days 1 and 8. Both regimens were recycled every 21 days.In total, 626 cycles were delivered (303 cycles of PEG and 323 cycles of PG), with a median of 4 cycles per patient in both arms. The objective response rate was 63% (95% confidence interval [95%CI], 49-71%) for PEG and 57% (95%CI, 43-67%) for PG, with the suggestion of a higher complete response rate in the PEG arm (18.6% and 4.3%, respectively). A similar time to disease progression (6 months in the PEG arm and 7 months in the PG arm) and a similar median survival (9.5 months in the PEG arm and 10 months in the PG arm) were observed in both arms. The PEG regimen was associated with more severe hematologic toxicity in terms of neutropenia, febrile neutropenia, and a higher rate of treatment delays and dose reductions, whereas nonhematologic toxicities did not differ between the two arms.According to the results of this Phase II randomized trial, the PEG regimen produced a higher complete response rate but more toxicity compared with the PG regimen in patients with extensive-stage or poor-prognosis, limited-stage small cell lung carcinoma.

Docetaxel was proven to be effective as second-line therapy for patients with advanced NSCLC after failure of platinum-based front-line chemotherapy. We designed this phase I/II study to define the Maximum Tolerated Dose of weekly docetaxel combined with weekly vinorelbine, and subsequently evaluate tolerability and activity of this schedule in NSCLC patients who were progressive after treatment with either cisplatin and gemcitabine or carboplatin and paclitaxel regimens. To be eligible for the study, patients were required to have a WHO performance status < or =2, failure after at least two cycles of first platinum-based chemotherapy, and no prior treatment with docetaxel and vinorelbine. A total of 27 patients were enrolled in this phase I/II study. A weekly docetaxel dose of 25 mg/m2 was recommended in combination with fixed vinorelbine dose of 20 mg/m2, and 24 patients were treated at this dose level. Severe neutropenia (62%) and febrile neutropenia (29%) were the most frequent toxicities, with 83% of patients requiring dose modification or delay. In the phase II study, 5 (21%) patients obtained a partial response, 8 (33%) patients had stable disease, whereas 10 (42%) patients progressed. After a median follow-up of 18.7 months, median survival was 8 months, with 30% surviving at 1 year. Regardless of the use of weekly docetaxel schedule, this regimen was highly myelosuppressive, and did not seem to improve response rate and survival compared to single-agent docetaxel. No further developments of this schedule are warranted.

Purpose: Our objective was to determine the activity in terms of response rate, surgical resectability, and the tolerability of the new three-drug combination gemcitabine–cisplatin–paclitaxel (GCP) in unresectable stage IIIA(N2) and IIIB non-small cell lung cancer (NSCLC). Patient and methods: Forty-two chemo-naive patients with stage IIIA(N2)–IIIB NSCLC, median age of 59 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and the ability to tolerate pneumectomy, received gemcitabine (Gem) 1000 mg/m2 IV days 1 and 8, cisplatin (CDDP) 50 mg/m2 IV days 1 and 8, paclitaxel 125 mg/m2 1 h infusion IV days 1 and 8, every 21 days for 3 cycles. After induction chemotherapy, patients were evaluated for surgery or definitive radiotherapy. Results: Grade 3–4 neutropenia was the main hematologic toxicity, occurring in 28% of patients. Grade 3–4 thrombocytopenia was observed in only 11% of cases. No neutropenic fever or bleeding episodes were recorded. Severe non-hematologic toxicity was uncommon. Thirty (71%, 95% CI: 57.2–84.7%) of the 42 eligible patients had objective responses (1 complete and 29 partial responses). After induction chemotherapy, 21 patients (50%) went to surgery. Complete resection was obtained in 16 patients (38%). Viable tumor was present in 18 of 21 resection specimens. In three cases only necrotic tumor cells were identified, for a pathological complete response of 7%. With a median follow-up of 13.9 months, median time to progression was 17.4 months, median survival 21.7 months and estimated 1-year survival 92%. Conclusions: GCP combination is active and well tolerated in locally-advanced, non-resectable NSCLC. The activity profile, in terms of response and surgical resection rate, is comparable to that obtained with standard doublets.

Objective: The objectives of this phase I/II study were to define the maximum tolerated dose (MTD), safety, and activity of cisplatin, etoposide, and gemcitabine (PEG) in the treatment of previously untreated patients with small-cell lung cancer (SCLC). Patients and Methods: Chemonaive patients received fixed doses of gemcitabine (1000 mg/m 2 on days 1 and 8) and cisplatin (70 mg/m 2 on day 2) and escalating doses of etoposide (starting dose of 50 mg/m 2 on days 3, 4, and 5) every 3 weeks. No prophylactic granulocyte colony-stimulating factors were used. Results: From September 1998 to April 2000, 56 patients with limited- or extensive-stage SCLC were enrolled and received a total of 235 cycles. Two different etoposide doses were tested in eight patients. At the second level (75 mg/m 2 ), two out of two patients experienced dose-limiting toxicities (neutropenia and thrombocytopenia) and no further dose-escalation was attempted, thus an etoposide dose of 50 mg/m 2 was defined as the MTD. In the subsequent phase II evaluation, 48 additional patients were enrolled, for a total of 54 patients treated at the MTD. Grade 3/4 neutropenia and thrombocytopenia occurred in 66.7 and 53.7% of patients, respectively. Non-hematologic toxicity was mild, with grade 3 diarrhea and fatigue as the main side effects. Two patients died of neutropenic sepsis (one at 75 mg/m 2 and the other at 50 mg/m 2 etoposide). Ten complete and 29 partial responses were reported, for an overall response rate of 72.2% (95% confidence interval, 56.6–85.0%). The median duration of response and median survival were 8.0 and 10 months, respectively, with a 1-year survival probability of 37.5%. Conclusions: The combination of PEG is feasible and well tolerated as front-line chemotherapy in SCLC. A randomized comparison of this triplet is underway.

The quality of life of lung cancer patients is affected by several factors related to the patients, stage of disease and treatment characteristics. For small-cell lung cancer (SCLC), the treatment is generally aggressive, primarily based on chemotherapy. Treatment strategy for non-small-cell lung cancer (NSCLC) is strongly dependent on the stage of the disease and ranges from surgery to palliative chemotherapy. Over the last few years, very little progress has been made in terms of survival. Therefore, the effect of treatment on quality of life has become progressively more relevant. Among the instruments for measuring quality of life, there are some specifically developed for lung cancer, such as the European Organization for Research and Treatment of Cancer (EORTC) LC-13 questionnaire, the Functional Assessment of Cancer Therapy (FACT-L) questionnaire and the Lung Cancer Symptom Scale (LCSS). Up to now, few randomised clinical trials have correctly evaluated quality of life. There are evident pitfalls associated with the use of frequently non-validated tools, and poor methods of data analysis, but quality-of-life evaluation is crucial and should be addressed through well-planned and well-conducted prospective clinical trials.

Background AIs represents the standard HT for the adjuvant treatment of post menopausal endocrine sensitive early breast cancer. A percentage of pts interrupt treatment because of toxicity. In this setting the switch to other AIs or tamoxifen (TAM) may represent an option to allow the prosecution of HT. We reviewed the main reasons for interruption of the AIs in our institution from 2006 to the present. Methods 236 pts with a minimum treatment time up of 6 months were considered eligible for analysis. Pts characteristics: median age 64 yrs (35-89), median follow up 24 months (6-28). Prior adjuvant CT: taxanes based: 47 pts, anthracyclines based: 43 pts. 118 pts (49%) had received letrozole (L), 101 (43%) anastrozole (A), 18 (8%) exemestane (E). An alternative HT (AIs or tamoxifen [T]) was offered to pts who wanted or needed to interrupt permanently the ongoing drug. Results According to the CTC NCI, arthralgia was the main toxicity observed (G1 19.4%, G2/3 5.5%/1.7%. Overall 24 out of 236 pts (10%) needed discontinuation of AIs as a result of toxicity. Grade 2 and 3 arthralgia was the main reason for discontinuation in 13/24 pts (54%). No differences in the incidence of arthralgia were noted in pts who had received taxanes or anthracyclines. Headache (n = 2), alopecia (n = 2), G3 itching (n = 2), diffuse skin reaction (n = 1) allergic reaction with hypertensive crisis (n = 1), xerostomia and xerophthalmia (n = 1), insomnia (n = 1) and somnolence (n = 1) were the other reasons for discontinuance. In the multivariate logistic regression analysis, age (65 yrs) and HT represent independent factors associated with the onset of arthralgia (respectively p = 0.006 and 0.008, OR 2.65, CI95: 1.32-5.31). 17/24 pts were switched to E, 5 to T and 1 each to L and A. In pts who switched to another AI we observed a reduction in the severity of the arthralgia but not its complete resolution. A complete resolution of symptoms was observed for the other toxicities except for allergic reactions that recurred after switching from L to A. Moreover, the patient with the diffuse skin reaction, chose discontinuation of HT. Conclusions In our analysis, 10% of pts discontinued AIs due to toxicity. Switching to alternative HT, and monitoring the toxicity, represent an option to offer to pts in order to avoid a premature and permanent interruption of an effective treatment. Disclosure All authors have declared no conflicts of interest.