Streptozocin can impair renal function. The purpose of this study was to evaluate the evolution of renal function in patients receiving this anti-mitotic for the treatment of locally advanced/metastatic digestive well differentiated neuroendocrine tumours. A prospective and a retrospective cohort of patients with normal baseline renal function were analysed. The primary endpoint was the incidence of a decrease in the estimated glomerular filtration rate ≥ 25% during treatment. Secondary endpoints were the evaluation of glomerular filtration rate changes, the impact of combined nephrotoxic treatments, other toxicities, compliance, and the objective response rate. After screening 142 patients, 27 were included in the prospective and 84 in the retrospective cohort. A decrease in estimated glomerular filtration rate ≥ 25% was observed in 32 patients (30%): respectively four (15.4%) and 28 patients (34.1%) among respectively 26 and 82 patients with numerous measures (P = 0.0097). Altogether, 39 patients (35%) experienced grade 1-2 renal toxicity, while no grade 3-4 occurred in the prospective and 1 occurred in the retrospective cohort. Renal toxicity was more frequent in the retrospective cohort with a less careful follow up. As best responses, objective response was achieved in 27% of patients with pancreatic primary tumours, disease control in 78.9% of patients with pancreatic primary tumours, in 87% of those with small bowel tumours and in 72.7% of patients with other primary locations. Strongly recommended for pancreatic NET, streptozocin is associated with frequent mild renal toxicity but low occurrence of renal impairment in patients with baseline normal renal function and under adequate hydration.

Fluropyrimidine monotherapy is an option for some patients with inoperable metastatic colorectal cancer. Unlike bevacizumab, the addition of aflibercept, an antibody acting as an anti-angiogenic agent, has never been evaluated in this context. The aim of the study was to determine whether aflibercept could increase the efficacy of fluoropyrimidine monotherapy without increasing toxicity. This multicenter phase II non-comparative trial evaluated the addition of aflibercept to infusional 5-fluorouracil/folinic acid (LV5FU2 regimen) as first-line treatment in patients unfit to receive doublet cytotoxic chemotherapy. The primary endpoint was 6-month progression-free survival (PFS). The clinical hypotheses expected a PFS rate at 6 months of over 40% (60% expected). A total of 117 patients, with a median age of 81 years, were included: 59 in arm A (LV5FU2-aflibercept) and 58 in arm B (LV5FU2 alone). Six-month PFS was 54.7% in both arms (90% CI 42.5–66.5 in both). Median overall survival was 21.8 months (arm A) and 25.1 months (arm B). Overall toxicity was more common in arm A: grade ≥ 3 toxicity in 82% versus 58.2%. Given the 6-month PFS, the study can be considered positive. However, the toxicity of aflibercept in this population was high, and continuation of the trial into phase III is not envisaged.

4110 Background: Neoadjuvant chemotherapy in a perioperative setting has proven valuable in locally advanced resectable colon cancer (CC) in terms of toxicity, postoperative morbidity and downstaging, but its effect on oncological outcomes remains uncertain. Methods: Prodige 22 was a randomized multicenter phase II trial in patients with resectable high-risk T3, T4 and/or N2 CC on baseline CT-scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type (wt) patients a third arm testing perioperative FOLFOX-cetuximab was added. Primary endpoint was the Tumor Regression Grade. Secondary endpoints were 3-years overall (OS), disease-free survival (DFS) and time to recurrence (TTR). Results: 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients (control, n = 52; FOLFOX peri-op n = 52) represented our intention-to-treat population. In the FOLFOX peri-op group, 96% received the schedule 4 cycles prior to surgery and all but one underwent adjuvant FOLFOX for a total of 12 cycles. In the control arm, 38 patients received adjuvant FOLFOX (1 postoperative death and 13 low-risk stage II patients). Median follow-up was 54.3 months [48.5-57.2]. Nineteen deaths and 26 disease recurrences were observed leading to a 3 years-OS of 90.3% in both arms (p = 0.7) and to a 3-years DFS of 76.8% and 69.2% in the peri-op and control arm respectively (p = 0.6). A trend to a better TTR in the peri-op arm was observed with a 3-years TTR of 82% as compared to 72% in the control arm (p = 0.3). No benefit from adding Cetuximab was observed in the 16 RAS-wt treated patients. Conclusions: In this pilot randomized study, perioperative FOLFOX chemotherapy has no detrimental effect on long term oncological outcomes and may be an option for some patients with locally advanced CC. A pooled analysis of randomized trials testing peri-operative strategies in this setting is warranted. Clinical trial information: NCT01675999 .