ABSTRACT
BACKGROUND: FOLFIRINOX regimen is the first-line reference chemotherapy (L1) in advanced pancreatic ductal adenocarcinoma (aPDAC). FOLFOXIRI, a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil, has demonstrated efficacy and feasibility in colorectal cancer. AIM: To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice. METHODS: Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions, with either FOLFOXIRI (n = 165) or FOLFIRINOX (n = 124) regimens. FOLFOXIRI consisted of irinotecan (165 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2) and 5-fluorouracil (3200 mg/m2 as a 48-h continuous infusion) every 2 wk. Ninety-six pairs of patients were selected through propensity score matching, and clinical outcomes of the two treatment regimens were compared. RESULTS: Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts, respectively. After propensity score matching, survival rates remained similar between the two regimens in terms of overall survival (hazard ratio = 1.22; P = 0.219) and progression-free survival (hazard ratio = 1.27; P = 0.120). The objective response rate was 37.1% in the FOLFOXIRI group vs 47.8% in the FOLFIRINOX group (P = 0.187). Grade 3/4 toxicities occurred in 28.7% of patients in the FOLFOXIRI cohort vs 19.5% in the FOLFIRINOX cohort (P = 0.079). FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events. Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5% with both regimens. CONCLUSION: FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX. The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.
ABSTRACT
Genetic instability is one part of the oncogenic process. Gene mutations involved in DNA repair mechanisms can promote this genetic instability and participate in oncogenesis and metastatic progression. In prostate cancer, DNA repair abnormalities mainly correspond to somatic or constitutional mutations of the BRCA2 and ATM genes. Therapeutic management of metastatic castration-resistant prostate cancer (mCRPC) is currently based on new hormonal therapies (abiraterone, enzalutamide) and taxane-type chemotherapy (docetaxel or cabazitaxel). Preliminary data tend to indicate a specific activity of agents causing DNA breaks (platinum salts) and PARP inhibitors in patients with these DNA repair abnormalities. The frequency of DNA repair gene mutations in patients with prostate cancer (around 20%) and the antitumor response of PARP inhibitors make it a possible short-term therapeutic strategy with several registering clinical trials ongoing.
