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. Copyright 2002 American Cancer Society.
BACKGROUND: Pegylated liposomal doxorubicin (PEG-LD) and gemcitabine have single-agent activity in breast and ovarian carcinomapatients. 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. Copyright 2002 American Cancer Society.
Authors: R-D Hofheinz; A Willer; A Weisser; U Gnad; S Saussele; S Kreil; J T Hartmann; R Hehlmann; A Hochhaus Journal: Br J Cancer Date: 2004-05-17 Impact factor: 7.640