CPT-11 for bile-duct and gallbladder carcinoma: A phase II North Central Cancer Treatment Group (NCCTG) study

Background. Bile-duct and gallbladder carcinomas are rare cancers. Once they have spread beyond the point of surgical resectability, no therapies have shown meaningful long-term benefit. These cancers are typically refractory to standard chemotherapy agents. Based on preclinical work showing activity of CPT-11, we performed a phase II trial to assess its activity in patients with bile-duct or gallbladder carcinomas. Methods. Patients with histologic or cytologic evidence of locally advanced or metastatic bile-duct or gallbladder carcinoma were potentially eligible for this study. Patients meeting study eligibility and who signed an informed consent were given CPT-11 125 mg/m² weekly for 4 wk followed by a 2-wk break from therapy. The starting dose of CPT-11 was later reduced to 100 mg/m² grade IV toxicity. Patients continued on treatment if they showed evidence of benefit and tolerated therapy. Results. A total of 39 patients were enrolled, and 36 were evaluable. The overall confirmed response rate was 8%. One CR and two PRs were seen. A high frequency of toxicity was seen. However, no unusual or unexpected toxicities occurred. Conclusion. CPT-11 is ineffective therapy for patients with locally advanced or metastatic bile-duct or gallbladder carcinoma.