A Phase I Study of Capecitabine Combined with CPT-11 in Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes

Abstract

Objective: A dose escalation study of biweekly irinotecan (CPT-11) combined with capecitabine was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) for metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Methods: Escalating doses of CPT-11 (80-120 mg/m²) were administered on days 1 and 15. Capecitabine was administered at a fixed dose of 1,657 mg/m²/day for 21 consecutive days, followed by 7 days of rest. We treated 3-6 patients at a particular dose level until the MTD was determined. Results: Twenty patients were treated. The MTD was determined to be 100 mg/m², as 3 of 6 patients developed dose-limiting toxicities, grade 3 leukopenia, neutropenia, photophobia, fatigue and diarrhea. The RD for the phase II study was thus determined to be 90 mg/m². The response rate was 41.7%. Conclusions: Combination therapy with CPT-11 and capecitabine was well tolerated with a promising response rate for MBC that had been treated previously with anthracyclines and taxanes. A multi-center phase II study is warranted to evaluate the efficacy and safety of this combination therapy with pharmacokinetic assessment.

Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase

“…Two small, single-arm clinical trials have specifically assessed the use of non-liposomal irinotecan monotherapy in patients with mBC, with reported ORRs of 5.6% and 23% [20,21]. Studies of non-liposomal irinotecan in combination with a chemotherapeutic agent in patients with mBC have reported ORRs ranging from 11 to 58.3% [22][23][24][25][26][27][28][29]. In addition, in a small-scale pilot study that assessed the use of multi-omic profiling of target tumors to guide treatment selection in patients with mBC, the most frequently selected treatment was irinotecan based on identified topoisomerase I expression in 12 of 25 evaluated patients (7 received irinotecan combination therapy; 5 received irinotecan monotherapy) [30].…”

Efficiency of Protective Interventions on Irinotecan-Induced Diarrhea: A Systematic Review and Meta-Analysis

“…Irinotecan, a semisynthetic derivative of camptothecin, is an anticancer drug that inhibits nucleic acid synthesis by targeting topoisomerase I. 1 , 2 It has been widely used in treating various solid tumors in adults and children, 3 , 4 including colorectal cancer most commonly, 5 , 6 as well as lung cancer, 7 breast cancer, 8 sarcoma, 3 , 4 esophageal cancer, 9 pancreatic cancer, 10 cholangiocarcinoma, 11 gastric cancer, 12 urothelial cell carcinoma, 13 etc. Experimental and clinical studies reveal that irinotecan not only can be used in monotherapy, 14 but also can be used in combination with cytotoxic agents (eg, 5-fluorouracil and oxaliplatin), monoclonal antibodies (eg, cetuximab and bevacizumab), kinase inhibitors (eg, fruquintinib, apatinib, dasatinib, regorafenib, and sunitinib), and cell-cycle checkpoint inhibitors.…”