Annals of Oncology 15:478-483, 2004
© 2004 European Society for Medical Oncology
Original Paper |
Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial
Received 2 August 2003; revised 22 October 2003; accepted 16 December 2003Background:
Patients with advanced biliary tract carcinoma face a particularly dismal prognosis, and no standard palliative chemotherapy has yet been defined. Among several different single agents, mitomycin C and, more recently, the oral fluoropyrimidine capecitabine and the nucleoside analogue gemcitabine, have been reported to exert antitumour activity. In view of a potential drug synergy, the present randomised phase II trial was initiated. The aim was to investigate the therapeutic efficacy and tolerance of mitomycin C (MMC) in combination with gemcitabine (GEM) or capecitabine (CAPE) in previously untreated patients with advanced biliary tract cancer.
Patients and methods:
A total of 51 patients were entered in this study and randomly allocated to treatment with MMC 8 mg/m2 on day 1 in combination with GEM 2000 mg/m2 on days 1 and 15 every 4 weeks, or MMC 8 mg/m2 on day 1 plus CAPE 2000 mg/m2/day on days 1–14, every 4 weeks. In both arms, chemotherapy was administered for a total of 6 months unless progressive disease occurred earlier.
Results:
Pretreatment characteristics were well balanced between the two treatment arms. The overall independent review committee-confirmed response rate among those treated with MMC + GEM was 20% (five of 25) compared with 31% (eight of 26) among those treated with MMC + CAPE. Similarly, median progression-free survival (PFS; 4.2 versus 5.3 months) and median overall survival (OS; 6.7 versus 9.25 months) tended to be superior in the latter combination arm. Chemotherapy was fairly well tolerated in both arms, with a comparably low rate of only grade 1 and 2 non-haematological adverse reactions. Also, only four (17%) patients in both treatment arms experienced grade 3 leukocytopenia, and three (13%) and four (17%) had grade 3 thrombocytopenia in the MMC + GEM and MMC + CAPE arm, respectively.
Conclusions:
The results of this study indicate that both combination regimens are feasible, tolerable and clinically active. The MMC + CAPE arm, however, seems to be superior in terms of response rate, PFS and OS, and should therefore be selected for further clinical investigation in advanced biliary tract cancer.
1 Division of Clinical Oncology, Department of Internal Medicine I, 2 Department of Surgery, and 3 Division of Gastroenterology & Hepatology, Department of Internal Medicine IV, Vienna University Hospital, Vienna; 4 Department of Surgery, Wr Neustadt General Hospital, Wr Neustadt; 5 Department of Surgery, Neunkirchen General Hospital, Neunkirchen, Austria
Key words: advanced biliary tract cancer, capecitabine, chemotherapy, gemcitabine, mitomycin C
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