Efficacy and safety of capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated pancreatic, gallbladder, and bile duct carcinoma.

Purpose: Preclinical data indicate the improvement of the antitumor activity of capecitabine by mitomycin C and docetaxel through upregulation of thymidine phosphorylase activity. Therefore, we have established a combination regimen of these drugs (DocMitoCape), which demonstrated preliminary activity especially in bile duct and pancreatic carcinoma.

Methods: Here we report the safety and efficacy of the DocMitoCape regimen in pre-treated patients with gallbladder, bile duct, or pancreatic carcinoma. Treatment consisted of capecitabine (2,000 mg/m(2) days 1-14) in combination with docetaxel (40 mg/m(2) day 1) and mitomycin C (4 mg/m(2) day 1). Cycles were repeated on day 22. Toxicity was graded according to NCI-CTC criteria, and the antitumor activity was assessed by RECIST criteria.

Results: Twenty-eight pre-treated patients with a median age of 59 suffering from pancreatic, gallbladder, intra- (IHCCC) or extrahepatic (EHCCC) bile duct carcinoma were included. Eleven patients had received ≥2 lines of prior chemotherapy. A total of 183 and a median of six cycles were administered (range 1-21). The mean dose intensity was as follows (cycles 1-2/3-4; %): capecitabine 97/92, docetaxel 100/100, mitomycin C 99/100. Main adverse events grades 2/3/4 were (n): leukocytopenia 3/2/2, anemia 13/4/0, thrombocytopenia 3/1/0, nausea/vomiting 2/1/0, diarrhea 5/1/0, hand-foot-skin reaction 7/0/0. Six patients achieved partial and seven patients minor remissions, while six patients had stable disease adding to a tumor control rate of 68%. Median progression-free and overall survival was 4.5 (range 1.0-44.9) and 6.8 months (range 1.5-44.9), respectively, calculated from the start of treatment.

Conclusion: In all, the DocMitoCape regimen exhibited a favorable safety profile and a high rate of tumor stabilizations in patients with pre-treated gallbladder, bile duct and pancreatic carcinoma. It might be considered after failure of standard regimens in these types of cancer.