Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial

Abstract

Background No standard treatment is available for advanced biliary tract cancer (BTC) after first-line therapy with gemcitabine plus cisplatin (GEMCIS). The objective of this study was to evaluate safety and anti-tumour activity of fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) as salvage treatment in patients with previously treated advanced BTC. Methods In this two-stage phase 2 study, patients with advanced BTC who had disease progression or unacceptable toxicity after ≥3 cycles of GEMCIS were eligible. Primary endpoints were safety and efficacy (defined as objective response rate, ORR). In stage one, ten patients were treated with FOLFIRINOX every 2 weeks. In stage two, an additional 20 patients were enrolled at a starting dose as defined in stage one, provided that in stage ≥1 objective response or ≥2 stable diseases were observed and ≤3 patients had serious adverse events (SAEs) within the first 6 weeks of treatment. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results Forty patients were screened for eligibility and 30 patients were enrolled. In stage one, one patient had a partial response and five patients had stable disease. One patient had a SAE during the first 6 weeks of treatment, and five patients required a dose reduction due to adverse events. The most common grade 3–4 adverse events in stage one were neutropaenia, mucositis and diarrhoea. Stage two was initiated with FOLFIRINOX in an adapted dose. In stage two, grade 3–4 neutropaenia, diarrhoea, nausea and vomiting were the most common adverse events. The ORR, median PFS and OS in all patients were 10%, 6.2 and 10.7 months, respectively. Conclusions In patients with advanced BTC who progressed after or were intolerant to GEMCIS, FOLFIRINOX can be administered safely and could be considered as an option for salvage treatment in these patients. Clinical trial registration ClinicalTrials.gov Identifier NCT02456714.

Overview of current targeted therapy in gallbladder cancer

“…It is noticeable that some clinical trials have shown that combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) yield promising results in patients with BTC. 21 , 22 However, none of the single program has been widely offered, since unexpected responses were deliberately taken into account, such as systemic toxicity, insufficient drug responses, and drug resistance. 23 Therefore, there are currently a large number of preclinical and clinical researches that are adding significant efforts in order to define the overall benefit of drug treatment even in the presence of adversary responses, which can be otherwise governed at a minimal level.…”

Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials

“…To improve therapeutic efficacy, more potent combination chemotherapy and in combination with targeted agents were also tested, including irinotecan and oxaliplatin plus 5-fluorouracil/leucovorin (FOLFIRINOX), and the application of capecitabine, irinotecan and gemcitabine plus bevacizumab [ 26 ]. In a single-arm phase II trial, 30 patients were enrolled who had disease progression or intolerance under GC treatment benefited from FOLFIRINOX treatment, with a median PFS and OS of 6.2 and 10.7 months, respectively [ 27 ].…”

Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm

“…However, a recent retrospective analysis of two large multicenter prospective cohorts suggested that monotherapy with 5-FU is as active as 5-FU doublets [ 18 ]. Chemotherapy intensification with the addition of irinotecan to FOLFOX (FOLFIRINOX), studied in a phase II trial in previously treated patients, reported a modest ORR, median PFS, and OS of 10%, 6.2, and 10.7 months, respectively [ 19 ]. A phase II study in refractory patients with a newer chemotherapeutic agent, TAS-102 (trifluridine and tipiracil), reported a median PFS and OS of 3.8 and 6.1 months, respectively, but no objective responses [ 20 ].…”