title: Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma.
abstract: OBJECTIVE
  To estimate the maximum-tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with irinotecan at 40 mg/m(2) daily for 3 days in the treatment of relapsed or refractory acute leukemia or lymphoma.
  
  
  METHODS
  Patients with leukemia or lymphoma were escalated in separate strata. Stratum I consisted of 11 patients, median age of 47 years (range, 18 to 68 years), with relapsed or refractory leukemia. Stratum II contained nine patients, median age of 48 years (range, 39 to 68 years), who had refractory non-Hodgkin's lymphoma. Patients received irinotecan at 40 mg/m(2) daily for 3 days, beginning just before the first dose of gemcitabine. Gemcitabine was given at 10 mg/m(2)/min, with the total duration adjusted following a modified continuous reassessment model.
  
  
  RESULTS
  Severe myelosuppression and stomatitis/esophagitis were the most serious hematologic and nonhematologic toxicities. Several patients developed febrile neutropenia, nausea, or vomiting. In both strata, the maximum recommended duration of infusion of gemcitabine was 12 hours delivered at 10 mg/m(2)/min (7,200 mg/m(2)). The overall response rate for one cycle of this therapy in this phase I trial for patients with leukemia was 18% (95% confidence interval, 8% to 45%), and for those with lymphoma, 33% (95% confidence interval, 17% to 66%).
  
  
  CONCLUSIONS
  A prolonged infusion of gemcitabine at 10 mg/m(2)/min for 12 hours with 3 days of irinotecan at 40 mg/m(2)/d is a tolerable induction regimen for patients with acute leukemia or lymphoma. Stomatitis/esophagitis should be anticipated; however, this regimen may induce responses in patients with difficult-to-treat hematologic malignancies.
authors.affiliation: Division of Medical Oncology and Transplantation, Duke University Medical Center, and the Duke Oncology Consortium, Durham, NC 27710, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bass
authors.forename: Jon P
authors.initials: JP
authors.lastname: Gockerman
authors.forename: Eve
authors.initials: E
authors.lastname: Hammett
authors.forename: Carlos M
authors.initials: CM
authors.lastname: DeCastro
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Gary L
authors.initials: GL
authors.lastname: Rosner
authors.forename: Nancy
authors.initials: N
authors.lastname: Payne
authors.forename: Patti
authors.initials: P
authors.lastname: Davis
authors.forename: Traci
authors.initials: T
authors.lastname: Foster
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004941:Esophagitis / Q000139:chemically induced; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D007938:Leukemia / Q000188:drug therapy*; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine