A Phase I study of bortezomib plus irinotecan in patients with advanced solid tumors


  • Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18–21, 2002, Orlando, Florida, and the 39th Annual Meeting of the American Society of Clinical Oncology, May 31 to June 3, 2003, Chicago, Illinois.



The authors conducted a Phase I dose-finding trial to study the use of combined bortezomib plus irinotecan in patients with advanced solid tumors.


Patients who had received ≥1 prior chemotherapy regimen were eligible. Patients received bortezomib (1.0 mg/m2, 1.3 mg/m2, or 1.5 mg/m2) on Days 1, 4, 8, and 11 and received irinotecan (from 50 mg/m2 to 125 mg/m2) on Days 1 and 8 of each 21-day cycle for a maximum of 8 cycles. Bortezomib followed irinotecan on coadministration days in Cycle 1 and Cycles 3 through 8 but preceded irinotecan in Cycle 2 to assess the effect of administration sequence on bortezomib pharmacodynamics.


Fifty-one enrolled patients with malignancies, including colorectal cancer (n = 23 patients), lung cancer (n = 6 patients), gastroesophageal cancer (n = 6 patients), and pancreatic cancer (n = 3 patients), received ≥1 dose of study drug. Nausea, vomiting, and diarrhea were the principal dose-limiting toxicities and led to the maximum tolerated doses of 1.3 mg/m2 bortezomib and 125 mg/m2 irinotecan. The most common grade ≥3 bortezomib-related nonhematologic adverse events were fatigue (n = 5 episodes), diarrhea (n = 4 episodes), and nausea (n = 4 episodes). grade ≥3 bortezomib-related hematologic adverse events included neutropenia (n = 6 episodes) and thrombocytopenia (n = 4 episodes) and rarely were dose limiting. Of 34 evaluable patients, no objective responses according to the Response Evaluation Criteria in Solid Tumors were seen; 10 patients achieved stable disease. The degree of proteasome inhibition in whole blood indicated that the biologic activity of bortezomib was unaffected by irinotecan coadministration.


The results of this Phase I study in patients with solid tumors indicated that bortezomib at a dose of 1.3 mg/m2 on Days 1, 4, 8, and 11 plus irinotecan at a dose of 125 mg/m2 on Days 1 and 8 every 21 days were the recommended Phase II doses. Cancer 2006. © 2006 American Cancer Society.