Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial.
BACKGROUND
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.


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.
Division of Clinical Oncology, Department of Internal Medicine I, Vienna University Hospital, Vienna, Austria. gabriela.kornek@akh-wien.ac.at
G V
GV
Kornek
B
B
Schuell
F
F
Laengle
T
T
Gruenberger
M
M
Penz
K
K
Karall
D
D
Depisch
F
F
Lang
W
W
Scheithauer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine