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Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies
Author(s) -
Fracasso Paula M.,
Blum Kristie A.,
Tan Benjamin R.,
Fears Carole L.,
Bartlett Nancy L.,
Arquette Matthew A.,
Clark Romnee S.
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10937
Subject(s) - gemcitabine , medicine , rash , nausea , refractory (planetary science) , gastroenterology , stomatitis , toxicity , pharmacology , chemotherapy , physics , astrobiology
BACKGROUND Pegylated liposomal doxorubicin (PEG‐LD) and gemcitabine have single‐agent activity in breast and ovarian carcinoma patients. We conducted a Phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in patients with advanced malignancies. METHODS Twenty‐six patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of PEG‐LD 20 mg/m 2 and gemcitabine 1000 mg/m 2 administered on Days 1 and 15 of a 28‐day cycle. RESULTS The MTD was PEG‐LD 20 mg/m 2 and gemcitabine 2000 mg/m 2 administered on Days 1 and 15 of a 28‐day cycle. Dose‐limiting toxicity, a Grade 3 rash, was observed in one patient during Cycle 1 and Grade 3 stomatitis and a rash were observed in a second patient during Cycle 2 after administration of PEG‐LD 25 mg/m 2 and gemcitabine 2000 mg/m 2 . Other side effects included palmar–plantar erythrodysesthesia, nausea, and fatigue. One complete and two partial responses were observed. CONCLUSIONS The recommended Phase II dose is PEG‐LD 20 mg/m 2 with gemcitabine 2000 mg/m 2 on Days 1 and 15 of a 28‐day cycle. A trial with this combination is currently ongoing at this institution comprising patients with refractory ovarian carcinoma. Cancer 2002;95:2223–29. © 2002 American Cancer Society. DOI 10.1002/cncr.10937