Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma

Adam J. Bass, Jon P. Gockerman, Eve Hammett, Carlos M. DeCastro, David J. Adams, Gary Rosner, Nancy Payne, Patti Davis, Traci Foster, Joseph O. Moore, David A. Rizzieri

Research output: Contribution to journalArticle

Abstract

Purpose: To estimate the maximum-tolerated duration of infusion of gemcitabine at 10 mg/m2/min in combination with irinotecan at 40 mg/m2 daily for 3 days in the treatment of relapsed or refractory acute leukemia or lymphoma. Patients and 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/m2 daily for 3 days, beginning just before the first dose of gemcitabine. Gemcitabine was given at 10 mg/m2/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/m2/min (7,200 mg/m2). 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%). Conclusion: A prolonged infusion of gemcitabine at 10 mg/m2/min for 12 hours with 3 days of irinotecan at 40 mg/m2/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.

Original languageEnglish (US)
Pages (from-to)2995-3000
Number of pages6
JournalJournal of Clinical Oncology
Volume20
Issue number13
DOIs
StatePublished - Jul 1 2002
Externally publishedYes

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irinotecan
gemcitabine
Lymphoma
Leukemia
Stomatitis
Esophagitis
Confidence Intervals
Febrile Neutropenia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma. / Bass, Adam J.; Gockerman, Jon P.; Hammett, Eve; DeCastro, Carlos M.; Adams, David J.; Rosner, Gary; Payne, Nancy; Davis, Patti; Foster, Traci; Moore, Joseph O.; Rizzieri, David A.

In: Journal of Clinical Oncology, Vol. 20, No. 13, 01.07.2002, p. 2995-3000.

Research output: Contribution to journalArticle

Bass, AJ, Gockerman, JP, Hammett, E, DeCastro, CM, Adams, DJ, Rosner, G, Payne, N, Davis, P, Foster, T, Moore, JO & Rizzieri, DA 2002, 'Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma', Journal of Clinical Oncology, vol. 20, no. 13, pp. 2995-3000. https://doi.org/10.1200/JCO.2002.08.166
Bass, Adam J. ; Gockerman, Jon P. ; Hammett, Eve ; DeCastro, Carlos M. ; Adams, David J. ; Rosner, Gary ; Payne, Nancy ; Davis, Patti ; Foster, Traci ; Moore, Joseph O. ; Rizzieri, David A. / Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma. In: Journal of Clinical Oncology. 2002 ; Vol. 20, No. 13. pp. 2995-3000.
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abstract = "Purpose: To estimate the maximum-tolerated duration of infusion of gemcitabine at 10 mg/m2/min in combination with irinotecan at 40 mg/m2 daily for 3 days in the treatment of relapsed or refractory acute leukemia or lymphoma. Patients and 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/m2 daily for 3 days, beginning just before the first dose of gemcitabine. Gemcitabine was given at 10 mg/m2/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/m2/min (7,200 mg/m2). 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{\%}). Conclusion: A prolonged infusion of gemcitabine at 10 mg/m2/min for 12 hours with 3 days of irinotecan at 40 mg/m2/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.",
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T1 - Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma

AU - Bass, Adam J.

AU - Gockerman, Jon P.

AU - Hammett, Eve

AU - DeCastro, Carlos M.

AU - Adams, David J.

AU - Rosner, Gary

AU - Payne, Nancy

AU - Davis, Patti

AU - Foster, Traci

AU - Moore, Joseph O.

AU - Rizzieri, David A.

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N2 - Purpose: To estimate the maximum-tolerated duration of infusion of gemcitabine at 10 mg/m2/min in combination with irinotecan at 40 mg/m2 daily for 3 days in the treatment of relapsed or refractory acute leukemia or lymphoma. Patients and 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/m2 daily for 3 days, beginning just before the first dose of gemcitabine. Gemcitabine was given at 10 mg/m2/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/m2/min (7,200 mg/m2). 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%). Conclusion: A prolonged infusion of gemcitabine at 10 mg/m2/min for 12 hours with 3 days of irinotecan at 40 mg/m2/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.

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