Abstract
Purpose
Advanced cancers of the bile duct and gallbladder carry an ominous prognosis. Rebeccamycin analogue (RA) is a novel antitumor antibiotic where phase I trials suggested clinical efficacy in patients with biliary cancers.
Methods
The primary objective was to determine the response rate to RA in patients with advanced gallbladder and bile duct tumors. Secondary endpoints were survival and pharmacokinetic characterization. RA was given at a dose 165 mg/(m2 day) × 5 days every 3 weeks.
Results
Forty-six patients were enrolled. Nine patients were removed from study before their first planned imaging study for response. Two patients had partial responses and 16 had stable disease. On an intent-to-treat analysis the median survival was 6.3 months. A >20% drop in CA19.9 was seen in 43% of patients with initial high levels. Grade 4 neutropenia and thrombocytopenia were seen in 35 and 5% of patients, respectively. Febrile neutropenia occurred in 16% of patients. The pharmacokinetic profile of this trial closely resembles those of prior phase I trials. Measured biliary concentrations of RA were as much as 100× greater than simultaneous plasma concentration.
Conclusion
Although RA has a response rate of 5% in advanced biliary cancers, it is associated with significant numbers of patients experiencing prolonged stable disease. Biliary concentrations of RA are significantly greater than plasma concentrations.
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Acknowledgments
Supported in part by grants U01 CA62502, MO1-RR-00080, 5K23 CA109348-01 (to AD) and TRF 23XS087A (to AD) from the National Institutes of Health to Case Western Reserve University and by grants P30CA47904 and M01-RR-00056 from the National Institutes of Health to the University of Pittsburgh Cancer Institute and Medical Center.
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Dowlati, A., Posey, J., Ramanathan, R.K. et al. Phase II and pharmacokinetic trial of rebeccamycin analog in advanced biliary cancers. Cancer Chemother Pharmacol 65, 73–78 (2009). https://doi.org/10.1007/s00280-009-1005-x
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DOI: https://doi.org/10.1007/s00280-009-1005-x