Background Oxaliplatin, irinotecan, 5-fluorouracil, and l -leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 or 4 adverse events associated with the standard dosage of FOLFIRINOX limits its widespread use in clinical practice. In this study, we were to evaluate the efficacy and safety of a modified FOLFIRINOX regimen as a first-line chemotherapy for Chinese patients with metastatic PC. Methods Patients with histologically confirmed primary metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–2 were recruited to receive the modified FOLFIRINOX regimen (intravenous infusion of oxaliplatin, 65 mg/m 2 ; irinotecan, 150 mg/m 2 ; l -leucovorin, 200 mg/m 2 ; and 5-fluorouracil, 2400 mg/m 2 , repeated every 2 weeks). The treatment was continued for 12 cycles unless the patient had progressive disease (PD), stable disease (SD) with symptom deterioration, unacceptable adverse events, or requested to terminate the treatment prematurely. The primary endpoint was objective response rate (ORR). Results Sixty-five patients were enrolled from July 2012 to April 2017 in three institutions, and they all received at least one cycle of chemotherapy, with a median of 8 cycles (range 1–12 cycles). No complete response was observed. Twenty-one (32.3%) patients had partial responses, and 27 (41.5%) had SD. The ORR and disease control rate of the study cohort was 32.3% and 73.8%. The estimated median overall survival and progression-free survival were 11.60 (95% confidence interval [CI] 8.76–14.44) and 5.77 (95% CI 5.00–6.54) months. Major grade 3 or 4 adverse events included neutropenia (12.3%) and diarrhea (6.2%). No treatment-related death was observed. Conclusions Modified FOLFIRINOX was well-tolerated and might be a promising option as first-line therapy for Chinese patients with metastatic PC. Trial registration ClinicalTrials.gov, NCT02028806. Registered 7 January 2014, https://clinicaltrials.gov/ct2/show/NCT02028806

Fibroblast growth factor receptor 4 (FGFR4) is a member of receptor tyrosine kinase family. A functional Gly388Arg (rs351855 G>A) polymorphism in FGFR4 gene causes a glycine-to-arginine change at codon 388 within the transmembrane domain of the receptor. Although the FGFR4 rs351855 G>A polymorphism has been implicated in cancer development, its association with cancer risk remains controversial. Here, we have systematically analyzed the association between the rs351855 G>A polymorphism and cancer risk by performing a meta-analysis of 27 studies consisting of 8,682 cases and 9,731 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. The rs351855 G>A polymorphism was associated with an increased cancer risk under the recessive model (OR=1.19, 95% CI=1.01-1.41). Stratified analysis by cancer type indicated the rs351855 G>A polymorphism was associated with an increased risk of breast and prostate cancer, but a decreased risk of lung cancer. This meta-analysis demonstrates the FGFR rs351855 G>A polymorphism is associated with increased cancer risk and suggests it could potentially serve as a chemotherapeutic target or biomarker to screen high-risk individuals.

BackgroundMonosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin‐based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin‐induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin‐based chemotherapy.MethodsIn total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI‐CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ‐CIPN20), time to grade 2 neurotoxicity (NCI‐CTCAE or the oxaliplatin‐specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3‐year disease‐free survival (DFS) and adverse events.ResultsThere were no significant differences between the arms in the rate of NCI‐CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ‐CIPN20 or time to grade 2 neurotoxicity using NCI‐CTCAE and the oxaliplatin‐specific neuropathy scale. GM1 substantially decreased participant‐reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3‐year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms.ConclusionPatients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977).

Purpose: Metastatic colorectal cancer patients with low epidermal growth factor receptor (EGFR) gene copy number are unlikely to respond to anti-EGFR monoclonal antibody (mAb) treatment. The objective of this study was to investigate EGFR fluorescence in situ hybridization (FISH) patterns of chromosome 7 disomy with efficacy of cetuximab therapy in metastatic colorectal cancer patients.Experimental Design: We detected the EGFR FISH patterns and KRAS status in 74 tumors from cetuximab-treated metastatic colorectal cancer patients and analyzed with response rate (RR) and progression-free survival (PFS).Results: One of the 16 (6.25%) patients with chromosome 7 homogeneous disomy (defined as FISH negative) had objective response to cetuximab. A total of 53(76.8%) patients with chromosome 7 pattern of variable ratios of disomy versus polysomy (defined as FISH positive) had a significantly higher RR (37.7% versus 6.25%; P ¼ 0.01), a trend towards longer PFS (4.5 versus 2.9 months; P ¼ 0.07). Among 54 KRAS wild-type patients, EGFR FISH-positive patients had significantly higher RR (51.3% versus 9%; P ¼ 0.01) and longer PFS (5.0 versus 2.3 months; P ¼ 0.02) than EGFR FISH-negative patients. However, among 20 KRAS mutant-type patients, there was no difference in RR (0% versus 0%) and PFS (2.5 versus 3.8 months; P ¼ 0.51) between EGFR FISH-positive and -negative patients.Conclusion: Our results show firstly that patients with EGFR FISH pattern of chromosome 7 disomy have a very low chance to benefit from cetuximab-based therapy. EGFR FISH pattern of chromosome 7 disomy may be as a negative predicative factor for cetuximab response in KRAS wild-type metastatic colorectal cancer patients. Clin Cancer Res; 17(2); 382-90. Ó2011 AACR.