Background:
Advanced biliary tract cancer (ABTC) is highly aggressive malignancy, with 5 year overall survival of <10%. Chemotherapy improves survival and quality of life in patients with ABTC, with gemcitabine/cisplatin the current standard first line treatment. In the second-line setting, evidence is limited to non-randomised phase II trials and retrospective reviews, with best supportive care the current standard of care. As this has been a traditionally difficult patient population to recruit for clinical trials, we undertook a pilot study to assess the feasibility of a phase II trial using capecitabine with nab-paclitaxel in patients with ABTC after failure of gemcitabine/cisplatin.
Methods:
Patients with histologically proven, unresectable biliary tract cancer, good performance status (ECOG 0-1), and progression on gemcitabine and a platinum were eligible. This is a single arm, open label, multicentre trial, with all patients receiving capecitabine (825mg/m2 bd PO D1-14 q21d) and nab-paclitaxel (125mg/m2 IV D1,8 q21d) until progression or unacceptable toxicity. The primary endpoint was feasibility of delivering the proposed regimen, measured by recruitment rate (time taken to recruit 10 patients) and treatment safety. Secondary objectives were disease control rate (complete +partial response + stable disease), progression free and overall survival, and quality of life outcomes.
Results:
10 patients enrolled within the planned 18 month recruitment period from 4 NSW cancer centres. Treatment generally well tolerated with grade III toxicities in 5 patients (including infection, cholangitis, obstruction and intestinal perforation) and no episodes of grade IV toxicity. Median treatment duration 4.3 months. Early efficacy signals promising, with a disease control rate of 80% (8/10), and median progression free and overall survival of 5.7 and 12.1 months respectively.
Conclusions:
Our pilot study demonstrates that combination capecitabine and nab-paclitaxel is feasible as a second-line treatment in ABTC. A formal phase II, with embedded translational sub-study, is planned to assess efficacy.