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International audience; Background/Aim: FOLFOX (5-Fluorouracile and oxaliplatin) exhibits promising activity in advanced welldifferentiated neuroendocrine tumors (NETs). This retrospective study aimed to analyze the outcome of metastatic enteropancreatic NETs patients treated with FOLFOX. Patients and Methods: We retrospectively identified patients treated with FOLFOX for NETs of enteropancreatic or unknown origin among those referred to our Regional Multidisciplinary Tumor Board. Results: Among 48 patients, most often pancreatic NETs (n=33, 68.8%), the median Ki67 index was 10%. The median number cycle of FOLFOX was 6 and median follow-up was 34.8 months. Disease control rate (DCR) was 83.3%. Median PFS and OS were 12.6 and 29.4 months respectively. Median chemotherapy break was 14.1 months. No significant difference was observed between PFS and the following criteria: Ki67 index, primary tumor site, alkaline phosphatase levels, primary tumor surgery and 18 F-FDG PET positivity. Conclusion: FOLFOX exhibits a high DCR and a short duration of treatment with a relative long chemotherapy break in patients with metastatic enteropancreatic NETs.

Background Because of the rarity of the condition, studies concerning the management of patients with squamous cell carcinoma of the anus with distant metastasis are scarce. The available studies indicate poor outcomes with exclusive chemotherapy. Objective Our aim was to evaluate the impact of multidisciplinary treatment on overall survival among patients presenting with metastatic squamous cell carcinoma of the anus. Design This was a retrospective study. Settings The study was conducted at a single French institution between 2000 and 2014. Patients Consecutive patients with histologically proven, newly diagnosed, or recurrent metastatic squamous cell carcinoma of the anus were included. Interventions Study interventions included multimodal therapy combining systemic chemotherapy and local ablative treatment to remove all metastases through surgery, radiofrequency ablation, or radiotherapy. Main outcome measures The primary outcome measure was overall survival. Results Fifty patients (median age, 62 years; men/women: 8/42) fulfilled the inclusion criteria, and 39 were available for Response Evaluation Criteria in Solid Tumors. Forty had metastatic relapse after previous treatment of localized disease, and 10 presented with synchronous metastasis. P16 status was not available. Patients received at least 1 chemotherapy regimen, including 5-fluorouracil-mitomycin C (n = 22), cisplatin-5-fluorouracil (n = 20), or 5-fluorouracil alone (n = 3). Thirteen also had surgical metastasectomy, 11 had radiotherapy, and 6 had radiofrequency ablation. Median overall survival was 20.0 months (95% CI, 18.2-21.8 mo), and median time to failure of strategy was 6.0 months (95% CI, 2.9-9.1 mo). Overall response rate was 56% (95% CI, 40%-73%). Outcomes from the 5-fluorouracil-mitomycin C and cisplatin regimens did not statistically differ. Patients treated with multimodal therapy had a median overall survival of 22.0 months (95% CI, 15.3-28.6 mo) versus 13.0 months (95% CI, 9.5-16.5 mo; p = 0.002). Median time to failure of strategy was 10.0 months (95% CI, 4.2-15.7 mo) versus 5.0 months (95% CI, 2.8-7.2; p = 0.007). After 2 years, 40% of patients with multimodal treatment and 20% of those without ablative treatment were alive. Limitations This study is limited by its retrospective design and modest sample size. Conclusions Stage IV squamous cell carcinoma of the anus outcomes are poor, but first-line chemotherapy can enable good response rates. Other treatment modalities, including surgery, radiotherapy, and thermoablation, should be considered, because they may provide a survival advantage. See Video Abstract at http://links.lww.com/DCR/A336.

Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with various clinical presentations and evolution. NETs are often diagnosed at a late stage, when they are already metastatic. Treatment is currently based on traditional chemotherapies, such as streptozocin, with serious side effects. The favorable toxicity profile of the combination of 5-fluorouracil with oxaliplatin, together with its significant antitumor activity in several gastrointestinal malignancies, led to the evaluation of its efficacy and tolerability in patients with advanced grade 1/2 (G1/G2) NETs. The endpoints of the study were tumor response (according to the Response Evaluation Criteria in Solid Tumors 1.1), overall survival (OS), progression-free survival (PFS) and symptom improvement. From January, 2013 to January, 2015, during our Regional Multidisciplinary Tumor Board dedicated to NETs (RENATEN network), FOLFOX was recommended for the treatment of metastatic NETs as first-line therapy or after failure of other therapies. The inclusion criteria were metastatic, well-differentiated G1/G2 NETs, progressing within the last 3 months. Cases with previous antitumor therapy were allowed. The patients received modified FOLFOX-6 and were assessed every 3 months by computed tomography or magnetic resonance imaging examinations. A total of 31 patients were included. The median follow-up was 20 months [95% confidence interval (CI): 15-27]. Nine patients (29%) exhibited a partial response, and 13 (41%) achieved stable disease; the disease control rate was 70%. A total of 9 patients exhibited disease progression. The control rate was 78% for pancreatic and 65% for extrapancreatic NETs. The median OS was not reached; the 1- and 2-year OS rates were 89 and 70%, respectively (Fig. 1). No significant difference in OS was observed between the

IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI

5004 Background: Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective cohort studies suggest a decrease in PC incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in PC preclinical models, with increase apoptosis when added to DOCE. The addition of MET could enhance DOCE efficacy in mCRPC patients (pts). Methods: TAXOMET is a phase II prospective multicentric randomized controlled trial. Non-diabetic mCRPC pts were assigned 1:1 to receive DOCE 75mg/m2 every 21 days + prednisone (P) 5 mg twice a day and either MET 850mg twice a day (arm A) or placebo (arm B), up to 10 cycles. The primary end point was PSA response rate (≥50% decrease). Main secondary endpoints included objective response rate (ORR, according to RECIST v1.1), clinical and biological progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL). Comparisons between arm A and B were performed using Chi² test for qualitative data and Log-rank test for survival data. Results: From January 2013 to December 2015, 99 pts were randomized (50 pts in arm A and 49 pts in arm B) in 10 french centers, and 95 pts were evaluable. No difference was observed between arm A and arm B in PSA-response rate (72% in both arms), ORR (28% in both arms), clinical or biological mPFS (7.3 months vs 5.8 months p = 0.848) and mOS (24.2 months (95CI: 17.2 – 33.7) vs 19.7 months (95CI: 14.8 – 36.8), p = 0.53), respectively. There was no difference between arms in adverse events, except a trend for diarrhea to be more common with MET (70% in arm A vs 50% in arm B, p = 0.072), but few grade 3-4 events. There was no difference in QoL according to QLQ-C30 score between the two arms during the treatment period. Conclusions: This is the first prospective randomized controlled trial to evaluate the combination of MET with DOCE+P in mCRPC. The addition of MET has no meaningful clinical benefit in this setting. Clinical trial information: NCT01796028.

149 Background: There is no therapeutic consensus after failure of two drug lines for metastatic gastric adenocarcinoma. The theoretical benefit of a third-line chemotherapy has to be weighed with the potential toxicity it could generate. It is essential to have prognostic and predictive factors to better select the candidate patients for a 3rd line chemotherapy. Methods: The medical records of patients (pts) treated in our institute from 2008 to 2018 who received at least two chemotherapy lines have been retrospectively analyzed. The main objective was to look for prognostic factors after failure of two chemotherapy lines. The secondary objectives were to look for predictive factors of progression-free survival, global survival, and RECIST response in 3rd line. Results: Out of a total of 153 pts identified, 68 received at least 2 chemotherapy lines and were eligible for analysis (44%). A third line was initiated for 41 pts (27%). Overall survival from the date of failure of a 2nd line treatment was 4.4 months (95% CI: 3.2-6.2). The median of progression-free survival in 3rd line was 1.68 months (CI 95%: 1.5-3.5 months), 5% of the patients responded to the treatment. In multivariate analysis, a period of less than 12 months between the administration of the 1st line of chemotherapy and the failure of a 2nd line was associated with a Hazard Ratio (HR) for death of 2.7 (p < 0.001; 95% CI 1.44 – 5.1). Pts who did not receive a 3rd line and female patients had a HR for death of 3.7 (p < 0.001; CI 95%: 1,9–7.3), and 2.8 (p < 0.001; 95% CI: 1,3–5.8) respectively. For patients who started a 3rd line: a PS ≥ 2 increased the risk of progression by 4.05 (p < 0.001; 95% CI: 1.1–15.7). Conclusions: Nearly one-third of pts were able to receive a third line chemotherapy. However, the benefit of this chemotherapy is low given the RECIST response rate, and the short overall and progression-free survival medians. Our results suggest that the administration of a third-line chemotherapy should only be considered for pts with 12 months or older ongoing metastatic lesions and whose general health condition is unaltered.

497 Background: Recent reports demonstrate prognostic and predictive impacts of the location of the primary tumor in metastatic colorectal cancer (mCRC). Our retrospective analysis aimed to determine the influence of primary site on metastatic distribution and disease evolution. Methods: From our database all patients (pts) with mCRC (except transverse carcinoma) treated from 1/12/2007 to 1/12/2016 in our institution were collected. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS). Results: A total of 284 pts with available data were analyzed: 83 with Right-sided Colon Cancer (RCC) (29%), 123 with Left-sided Colon Cancer (LCC) (43%) and 78pts with Rectal Cancer (RC) (28%). Hepatic, lung, lymph nodes and peritoneal metastases were respectively found in 63%, 36%, 23% and 20% of the population. The incidence or number of liver metastases were not influenced by sidedness (p = 0.06), LCC presented more bilobar involvement compared to RCC and RC (p = 0.017). Peritoneal carcinomatosis was significantly correlated to colon cancer (p = 0.002), whereas lung metastases were more common in RC (p < 0.001). Patients with RCC more often presented distal lymph node involvement (p = 0.008). RAS mutation status was known for 241pts (80%), of those 110 (37%) were RAS mutated with no significant differences between RCC, LCC and RC (p = 0.4), BRAF mutation (p = 0.007) was more common in RCC. On a multivariable analysis, primary tumor resection (PTR) and complete response after first line therapy were associated with a better OS but only a trend was observed for LCC and RC. Lung, lymph and peritoneal metastasis were associated with worse OS (Table). Conclusions: These results suggests that mCRC had different clinical presentation at diagnosis, the association with molecular features may explain the independent prognostic factor for OS of the sidedness. [Table: see text]

Objective: Treating metastatic pancreatic cancer (MPC) remains a challenging issue. Maintenance therapy is a growing concept used in different types of cancer. Our retrospective analysis aims to evaluate the effectiveness and tolerability of early maintenance capecitabine administrated to patients with MPC treated with first-line FOLFIRINOX. Methods: 103 patients treated for MPC between November 2009 and July 2014 were retrospectively identified in our institution. Among them, 30 patients initially treated with a minimum of 4 and no more than 8 cycles of FOLFIRINOX, without signs of progression (every 14 days), received maintenance therapy with capecitabine until progression. Upon first progression (first progression-free survival, PFS1), patients were retreated with FOLFIRINOX or another scheme until second progression (second progression-free survival, PFS2). Results: Median OS was 17 months. Survival rates were 73% at 1 year (95% CI 0.59-0.91) and 25% at 2 years (95% CI 0.13-0.50). Median PFS1 was 5 months. Twenty-nine patients experienced disease progression during capecitabine treatment (96.7%). After disease progression, median PFS2 was 10 months. Considering the interval between the starting date of FOLFIRINOX treatment and second disease progression, the median time to treatment failure is 17 months. Conclusions: Maintenance with capecitabine seems effective without compromising FOLFIRINOX efficacy and allows obtaining very promising OS and PFS.

BACKGROUND. Docetaxel is a well-recognized drug in patients with hormone-refractory prostate cancer (HRPC), either alone or combined with estramustine. In this indication, a Phase II trial was conducted investigating a docetaxel-capecitabine combination. METHODS. Forty-six patients presenting with documented HRPC were enrolled in the study. The treatment regimen consisted of docetaxel (D) at a dose of 35 mg/m2/week (intravenously, 3 consecutive weeks) plus oral capecitabine (C) at a dose of 625 mg/m2 twice daily (Days 5–18) every 28 days for 4 cycles. The primary endpoint was the biological response defined as a reduction in prostate-specific antigen (PSA) level ≥50%. Secondary endpoints were overall survival, safety, and quality of life. RESULTS. Thirty of 44 assessable patients (68.2%) achieved a biological response, 14 of whom (31.8%) normalized their PSA value. The median overall survival time was 17.7 months (95% confidence interval, 15.8 to not reached). Four treatment cycles were completed by 87% of the patients. Hematologic toxicity was mild. The main Grade 3–4 toxicities were cutaneous toxicity (13.1%) and changes in nails (6.5%). Physical functioning and role scales were higher before treatment (P = .02 and P = .003, respectively), fatigue and diarrhea were more frequent during and after treatment (P = .0003 and P = .03, respectively), and pain was lower during and after treatment. CONCLUSIONS. The results of the current study demonstrated the high efficacy of the DC combination in patients with HRPC, and the associated good tolerability. This combination offers a new alternative to the docetaxel-estramustine combination. Further randomized trials are warranted. Cancer 2006. © 2006 American Cancer Society.

9511 Background: The purpose of this study is to analyse predictive factors of early death in older patients with cancer during 100 days after a geriatric comprehensive assessment (CGA) in order to...

4624 Background: Docetaxel monotherapy is active in hormone refractory metastatic prostate cancer. Pre-clinical models indicate a synergistic cytotoxicity between capecitabine and docetaxel. Recently, this association has proven survival benefits in advanced breast cancer. This multicenter phase II study reports on preliminary efficacy and safety data of docetaxel-capecitabine combination in hormone-refractory prostate cancer with metastases (HRPC). Methods: Eligible pts had histologically and biologically confirmed HRPC. Other requirements included a Karnofsky index of more than 50% and no prior chemotherapy except estramustine. Treatment consisted of 4 cycles of docetaxel 35mg/m2 on day 1, day 8, day 15 and capecitabine 1250mg/m2/day in 2 divided doses from day 5 to day 18 of each 28 days cycle. A minimum of 2 treatment cycles were required for response assessment. Biological efficacy was defined as a decline of >50% from baseline PSA levels. Clinical response was evaluated using RECIST criteria. Result...