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

Ali Belkouz, Judith de Vos-Geelen, Ron A A Mathôt, Ferry A L M Eskens, Thomas M van Gulik, Martijn G H van Oijen, Cornelis J A Punt, Johanna W Wilmink, Heinz-Josef Klümpen, Ali Belkouz, Judith de Vos-Geelen, Ron A A Mathôt, Ferry A L M Eskens, Thomas M van Gulik, Martijn G H van Oijen, Cornelis J A Punt, Johanna W Wilmink, Heinz-Josef Klümpen

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Change in tumour volume of…
Fig. 1. Change in tumour volume of target lesions.
*, The tumour diameter of this patient did not change over time. The dashed lines represent 20% increase or 30% decrease in tumour diameter.
Fig. 2. Kaplan–Meier curves of overall survival…
Fig. 2. Kaplan–Meier curves of overall survival and progression-free survival.
(a) overall survival (b) progression-free survival.

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