Phase I study of liposomal doxorubicin (Doxil) and cyclophosphamide in solid tumors.

INTRODUCTION

The purpose of this study was to determine the recommended phase II dose (RPTD) of the combination of cyclophosphamide and liposomal doxorubicin (Doxil).

PATIENTS AND METHODS

Eligibility criteria included: a diagnosis of non-hematologic cancer with no conventional effective therapy, normal renal, liver and bone marrow function, and ECOG performance status of 0-2. Both drugs were administered intravenously on day 1 of a 21-day cycle. The following doses (mg/m2) of Doxil and cyclophosphamide were tested: 30/500, 40/600, and 48/600.

RESULTS

Thirty-seven patients with a median age of 62 years (male:female 21:16) received 119 cycles of Doxil and cyclophosphamide. Hand-foot syndrome and mucositis were the dose limiting toxicities for this combination. Other major toxicities included neutropenia. The side effects to the combination were cumulative. The RPTD of Doxil and cyclophosphamide was 48 mg/m2 and 600 mg/m2, respectively. Three patients with adenocarcinoma of the stomach, fibrosarcoma of the stomach and renal cell carcinoma showed objective antitumor responses.

CONCLUSION

The toxicity profile of the combination of Doxil/cyclophosphamide differs significantly from that of non-liposomal doxorubicin plus cyclophosphamide. Major toxicities of the combination include the hand-foot syndrome, stomatitis and neutropenia.