TY - JOUR
T1 - A phase I trial of gemcitabine administered as a 96-h continuous intravenous infusion in patients with advanced carcinoma and lymphoma
AU - Rajdev, Lakshmi
AU - Goldberg, Gary
AU - Hopkins, Una
AU - Sparano, Joseph A.
N1 - Funding Information:
Supported in part by National Institute Of Health Grant P30CA13330 and by a grant from Eli Lilly, Inc. The authors also acknowledge Dr. Merrill Egorin, who reviewed the manuscript and provided helpful advice.
PY - 2006/9
Y1 - 2006/9
N2 - Background and objective: Preclinical data suggest gemcitabine may have schedule-dependent activity favoring prolonged infusion. We sought to determine the recommended phase II dose (RPTD) and toxicity of gemcitabine when given as a continuous intravenous (CIVI) over 96 h. Patients and methods: Gemcitabine was initially given at 1 mg/m2/d for 48, then 72, and finally 96 h. The dose was then increased to 2, 4, 6, 10, 15, 20, and 25 mg/m2/d. Dose levels of 7, 8, 9 mg/m2/d as 96-h infusion were added later after a protocol modification. After identifying the RPTD using an every 3-wk schedule, we then evaluated the feasibility of repeating the infusion every 2 wk, and then weekly for 3 of 4 wk. Results: Thirty-four patients with a variety of tumor types received a total of 126 cycles of therapy (median of 2 cycles, range 1-10 cycles). The RPTD was 8 mg/m2/d every 3 wk, and 6 mg/m2/d every 2 wk. The most common grade 2 or higher toxicities at all dose levels (≥ grade 2) included fever (n = 14), dyspnea (n = 7), mucositis (n = 6), hypotension (n = 6), nausea/vomiting (n = 6), and fatigue (n = 5). Neutropenia and/or thrombocytopenia were uncommon. Conclusion: Administration of gemcitabine as a 96-h infusion results in a markedly different toxicity profile and RPTD than when given by a conventional 30-min infusion. The RPTD was 8 mg/m 2/d (32 mg/m2/course) when given every 3 wk, or 6 mg/m2/d (24 mg/m2/course) when given every 2 wk.
AB - Background and objective: Preclinical data suggest gemcitabine may have schedule-dependent activity favoring prolonged infusion. We sought to determine the recommended phase II dose (RPTD) and toxicity of gemcitabine when given as a continuous intravenous (CIVI) over 96 h. Patients and methods: Gemcitabine was initially given at 1 mg/m2/d for 48, then 72, and finally 96 h. The dose was then increased to 2, 4, 6, 10, 15, 20, and 25 mg/m2/d. Dose levels of 7, 8, 9 mg/m2/d as 96-h infusion were added later after a protocol modification. After identifying the RPTD using an every 3-wk schedule, we then evaluated the feasibility of repeating the infusion every 2 wk, and then weekly for 3 of 4 wk. Results: Thirty-four patients with a variety of tumor types received a total of 126 cycles of therapy (median of 2 cycles, range 1-10 cycles). The RPTD was 8 mg/m2/d every 3 wk, and 6 mg/m2/d every 2 wk. The most common grade 2 or higher toxicities at all dose levels (≥ grade 2) included fever (n = 14), dyspnea (n = 7), mucositis (n = 6), hypotension (n = 6), nausea/vomiting (n = 6), and fatigue (n = 5). Neutropenia and/or thrombocytopenia were uncommon. Conclusion: Administration of gemcitabine as a 96-h infusion results in a markedly different toxicity profile and RPTD than when given by a conventional 30-min infusion. The RPTD was 8 mg/m 2/d (32 mg/m2/course) when given every 3 wk, or 6 mg/m2/d (24 mg/m2/course) when given every 2 wk.
KW - 96 h
KW - Gemcitabine
KW - Infusional
KW - Phase I
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U2 - 10.1385/MO:23:3:369
DO - 10.1385/MO:23:3:369
M3 - Article
C2 - 17018894
AN - SCOPUS:33749379982
VL - 23
SP - 369
EP - 376
JO - Medical Oncology and Tumor Pharmacotherapy
JF - Medical Oncology and Tumor Pharmacotherapy
SN - 0340-7004
IS - 3
ER -
