Abstract P5-10-13: Phase I Dose Escalation Study of Pirarubicin in Combination with Cyclophosphamide in Breast Cancer

Abstract

Abstract Background: Doxorubicin containing combination chemotherapy regimens are widely used for treatment of breast and other cancers. However, these regimens are associated with significant toxicities including myocardialdysfunction and alopecia. Analogues of doxorubicin are being developed to reduce these side effects. Pirarubicin is a more lipophilic derivative of doxorubicin, with a higher uptake rate of cells, lower cardiotoxicity and better antitumor efficacy in preclinical models. Purpose: We conducted a single-institution phase I clinical trial to determine the maximum-tolerated dose (MTD) and define the toxic effects and recommended dose (RD) of pirarubicin in combination with cyclophosphamide in patients with breast cancer. Patients and Methods: Patients who had received prior anthracycline therapy were excluded. Cohorts of three patients with breast cancer were treated with escalating doses of pirarubicin (40 to 70 mg/m2) intravenously administered every three weeks in combination with cyclophosphamide (60 mg/m2) for 4 or more cycles. Results: Eleven patients of stage I/II operable breast cancer received a total of 46 cycles of pirarubicin and cyclophosphamide as post-operative adjuvant chemotherapy. The most frequently reported treatment-related grade 2 adverse events were constipation (36%) and nausea (27%). There were no grade 3/4 events. Grade 2 leukocytopenia and grade 2 fatigue were dose-limiting at 70 mg/m2, the maximum-tolerated dose was 60 mg/m2. Grade 2 alopecia was reported in 60 and 70 mg/m2 pirarubicin group. Conclusion: At the MTD of 60 mg/m2 every 3 weeks, pirarubicin in combination with cyclophosphamide was associated with mild, reversible toxicity. The recommended phase II dose is pirarubicin 50 mg/m2 and cyclophosphamide 60 mg/m2 on day 1 every 21 days. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-13.