Phase I study of liposomal doxorubicin (Doxil) and cyclophosphamide in solid tumors.
BACKGROUND
The purpose of this study was to determine the recommended phase II dose (RPTD) of the combination of cyclophosphamide and liposomal doxorubicin (Doxil).


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.


CONCLUSIONS
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.
El-Rayes
Basil F
BF
Division of Hematology/Oncology, Wayne State University, Karmanos Cancer Institute, Detroit, MI 48201, USA.
Ibrahim
Dina
D
Shields
Anthony F
AF
LoRusso
Patricia M
PM
Zalupski
Mark M
MM
Philip
Philip A
PA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin; D003520:Cyclophosphamide