Clinical Assessment of 5-Fluorouracil/Leucovorin, Nab-Paclitaxel, and Irinotecan (FOLFIRABRAX) in Untreated Patients with Gastrointestinal Cancer Using Genotype-Guided Dosing.

Purpose: 5-Fluorouracil (5-FU)/leucovorin, irinotecan, and nab-paclitaxel are all active agents in gastrointestinal cancers; the combination, FOLFIRABRAX, has not been previously evaluated. UDP Glucuronosyltransferase 1A1 (UGT1A1) clears SN-38, the active metabolite of irinotecan. polymorphism reduces UGT1A1 enzymatic activity and predisposes to toxicity. We performed a trial to assess the safety and tolerability of FOLFIRABRAX with genotype-guided dosing of irinotecan.

Patients And Methods: Patients with previously untreated, advanced gastrointestinal cancers received FOLFIRABRAX with prophylactic pegfilgrastim every 14 days. , and patients received initial irinotecan doses of 180, 135, and 90 mg/m, respectively. 5-FU 2,400 mg/m over 46 hours, leucovorin 400 mg/m, and nab-paclitaxel 125 mg/m were administered. Doses were deemed tolerable if the dose-limiting toxicity (DLT) rate during cycle 1 was ≤35% in each genotype group. DLTs were monitored using a sequential procedure.

Results: Fifty patients enrolled, 30 pancreatic, 9 biliary tract, 6 gastroesophageal, and 5 others. DLTs occurred in 5 of 23 (22%) patients, 1 of 19 (5%) patients, and 0 of 7 patients. DLTs were all grade 3: diarrhea (3 patients), nausea (2 patients), and febrile neutropenia (1 patient). The overall response rate was 31%. Response rates in pancreatic, gastroesophageal, and biliary tract cancers were 34%, 50%, and 11%, respectively. Eighteen patients (36%) received therapy for at least 24 weeks.

Conclusions: FOLFIRABRAX with genotype-guided dosing of irinotecan is tolerable in patients with advanced gastrointestinal cancer and or genotypes. Too few patients were enrolled to provide conclusive results. Responses occurred across multiple tumor types.