Phase I evaluation of prolonged-infusion gemcitabine with fludarabine for relapsed or refractory acute myelogenous leukemia.
OBJECTIVE
The purpose of this study was to determine the maximum tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with fludarabine at 25 mg/m(2) daily for 5 days in the treatment of relapsed or refractory acute myelogenous leukemia.


METHODS
Eighteen patients with relapsed or refractory acute myelogenous leukemia were enrolled. The median age was 54.5 years (range, 21-80 years). Patients received a 30-min infusion of fludarabine at 25 mg/m(2) daily for 5 days. i.v. gemcitabine was given as a single infusion at 10 mg/m(2)/min with the duration adjusted following a modified continuous reassessment method.


RESULTS
After 18 patients, the maximum recommended duration of infusion of gemcitabine in combination with fludarabine was selected as a 15-h infusion given at 10 mg/m(2)/min (9,000 mg/m(2)). Severe stomatitis or esophagitis was the most common nonhematological dose-limiting toxicity. Myelosuppression was universal. Febrile neutropenia was common, and 3 of 18 (17%) patients developed bacteremia. Occasional nausea, vomiting, or diarrhea was also reported. There were three complete responses and two partial responses for an overall response rate of 28%.


CONCLUSIONS
Prolonged-infusion gemcitabine at a fixed dose rate of 10 mg/m(2)/min for 15 h with 25 mg/m(2)/day fludarabine for 5 days is a tolerable induction regimen for relapsed or refractory leukemia. Stomatitis, esophagitis, febrile neutropenia, and myelosuppression should be anticipated; however, this regimen may be beneficial in patients with relapsed or refractory leukemia.
Rizzieri
David A
DA
Duke University Medical Center, Division of Medical Oncology and Transplantation and the Duke Oncology Consortium, Durham, North Carolina 27710, USA. rizzi003@mc.duke.edu
Ibom
Valerie K
VK
Moore
Joseph O
JO
DeCastro
Carlos M
CM
Rosner
Gary L
GL
Adams
David J
DJ
Foster
Traci
T
Payne
Nancy
N
Thompson
Maria
M
Vredenburgh
James J
JJ
Gasparetto
Christina
C
Long
Gwynn D
GD
Chao
Nelson J
NJ
Gockerman
Jon P
JP
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D004941:Esophagitis / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012008:Recurrence; D013280:Stomatitis / Q000139:chemically induced; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000093542:Gemcitabine
D003841:Deoxycytidine; D014740:Vidarabine; C024352:fludarabine; D000093542:Gemcitabine