P-0143 The Role of Chemotherapy in Advanced Biliary Tract Cancers: Clinical Experience from a Specialist UK Cancer Centre

Abstract

ABSTRACT Introduction Since 2010, treatment of advanced biliary tract cancers (ABTC) has evolved with the results of the ABC-02 trial, which demonstrated that first-line chemotherapy with gemcitabine plus cisplatin (GEM-CIS) improves survival without the addition of substantial toxicity. There is no standard second line therapy for patients (pts) with progressive disease. We evaluated the outcome and toxicity of GEM-CIS as first line and FOLFOX-6 as second line therapy in pts with ABTC. Methods We retrospectively reviewed 36 pts with ABTC treated at Guy's Hospital, between May 2008 and February 2012. Of these, 32 pts received as first line GEM (1000 mgr/m2)- CIS (25 mgr/m2), each administered on days 1 and 8, every 3 weeks, for 8 cycles or until progression or unacceptable toxicities. Among the 14 pts who progressed and were eligible for second line therapy. 11 pts were treated with FOLFOX-6 (oxaliplatin 85 mgr/m2 and folinic acid 400 mgr/m2 on day 1, followed by a 5-FU bolus 400 mgr/m2 and 46-h infusion 2400 mgr/m2) every 2 weeks, for 12 cycles or until progression or unacceptable toxicities. The primary endpoint was median overall survival (mOS), and secondary endpoints were median progression free-survival (mPFS), tumour control rate (TCR)- [complete response (CR) plus partial response (PR) plus stable disease (SD)]- and toxicity. Results Pts had a median age of 65 years (range 35-79); 58% pts were women. Primary tumour sites of the 36 pts were extrahepatic (7), intrahepatic (14), gallbladder (11) and unknown (4). 23/36 pts immunophenotyped, with biliary type adenocarcinoma observed in 19, and intestinal type in 4 pts. The median number cycles of GEM-CIS administered was 4 (1-8). The mOS was 16.3 months (95%, CI 9.62-23.04), and the mPFS was 9.1 months (95%, CI 6.24-11.95). The TCR was 70%, including 13 patients with PR and 8 patients with SD. Neutropenia grade 3 and 4 was recorded in 26.7% of pts. When they relapsed, 11 pts were eligible to receive FOLFOX-6, 4 women and 7 men. A median number of 6 cycles (2-11) were administered. The mOS was 6.7 months (95%, CI 4.45-8.94), and the mPFS was 3.6 months (95%, CI 1.50-5.69). TCR observed was 45.5% (95%, CI 16.8-76.6). Among the 5 pts who responded, 2 pts achieved PR, one who had previously achieved PR and another who had progressed with GEM-CIS, and 3 patients achieved SD, who had previously achieved PR (1) and SD (2) with the first line. 4 pts who had progressed with GEM-CIS, did not respond with FOLFOX-6, and 2 pts who had achieved PR with GEM-CIS, progressed with FOLFOX-6. Neutropenia grade 3 and 4 was recorded just in 1 patient and grade 2 neurotoxicity was reported in 3 pts. Neither GEM-CIS nor FOLFOX-6 caused any treatment-related death. Conclusion We confirm that GEM-CIS is an effective and well-tolerated first line regimen for treatment of ABTC. FOLFOX-6 should be considered as a potential second-line therapy for pts who progress after GEM-CIS, and clinical trials to evaluate this further are warranted.