Phase I/II Trial of Combined Pegylated Liposomal Doxorubicin and Cyclophosphamide in Metastatic Breast Cancer

Conventional doxorubicin in combination with cyclophosphamide is active in breast cancer; however, use in metastatic disease is limited by significant toxicity and poor tolerability. This phase I/II trial (n = 30) demonstrated that pegylated liposomal doxorubicin with daily oral cyclophosphamide is an active and tolerable regimen with modest toxicity and reasonable efficacy. Introduction: Doxorubicin in combination with cyclophosphamide is active in breast cancer; however, its use in metastatic cancer is limited owing to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) was formulated to decrease the toxicity of conventional doxorubicin. We evaluated the safety and efficacy of PLD with metronomic oral cyclophosphamide. Patients and Methods: We conducted a single-arm open-label phase I/II study of PLD and oral cyclophosphamide in patients with metastatic breast cancer. In phase I, 3 escalating doses of PLD were planned (30, 35, and 40 mg/m(2)) with cyclophosphamide (60 mg/m(2) orally daily) to determine the maximum tolerated dose (MTD). In phase II, the MTD of PLD in combination of oral cyclophosphamide was used to assess the primary endpoint of overall clinical response rate and secondary endpoints of progression-free survival, overall survival, and adverse events. Results: Thirty patients were enrolled in the study (n = 6 in phase I and n = 24 in phase II). The MTD of PLD from phase I was 30 mg/m(2). The median progression-free and overall survival for the entire cohort were 6.4 months (95% confidence interval, 3.9 months to N/A) and 18.7 months (95% confidence interval, 15.1-31.5 months), respectively. A total of 21 (75%) patients had clinical benefit, including 6 (21%) patients with partial response and 15 (54%) patients with stable disease. The majority of toxicities were uncomplicated myelosuppression, and no infection or febrile neutropenia were noted in any patient. Conclusion: PLD in combination with daily oral cyclophosphamide is an active and tolerable regimen in metastatic breast cancer. (C) 2017 Elsevier Inc. All rights reserved.