Journal article
S-phase modulation by irinotecan : pilot studies in advanced solid tumors
Cancer chemotherapy and pharmacology, Vol.56(5), pp.447-454
2005
DOI: 10.1007/s00280-004-0951-6
PMID: 15947933
Abstract
Two studies of irinotecan (CPT-11) followed 24 h later by an antimetabolite were conducted. The objectives of the studies were: (1) to determine whether the increase in S-phase in tumor cells seen 24 h after CPT-11 administration in animal studies is seen in advanced solid tumors in patients, (2) to determine the dose of CPT-11 required to produce this effect, (3) to compare two methods (immunohistochemistry, IHC, for cyclin A, and DNA flow cytometry, FC) for evaluating S-phase in tumor biopsies from patients, and (4) to establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of CPT-11, given 24 h before gemcitabine (GEM, 1000 mg/m2). In one study CPT-11 was followed 24 h later by 5-fluorouracil (5-FU), 400 mg/m2 per week for 4 weeks every 6 weeks. Tumor biopsies were obtained before and 24h after CPT-11 administration before administration of 5-FU and assayed for S-phase by IHC for cyclin A and by FC. The starting dose of CPT-11 was 80 mg/m2 per week with subsequent exploration of 40 and 60 mg/m2 per week to establish the dose-effect relationship of the increase in tumor cells in S-phase. In the second study, CPT-11 was given 24 h before GEM 1000 mg/m2 per week for 2 weeks every 3 weeks. Doses of 20-80 mg/m2 were explored to establish the MTD and DLT and to study tumor cell S-phase in selected patients. CPT-11 80 mg/m2 produced a mean increase in S-phase by IHC for cyclin A of 137%. Lesser increases were seen with 40 and 60 mg/m2. CPT-11 followed 24 h later by 5-FU 400 mg/m2 per week for 4 weeks was well tolerated. In the study of CPT-11 followed by GEM 1000 mg/m2, 60 mg/m2 of CPT-11 was the MTD. © Springer-Verlag 2005.
Details
- Title: Subtitle
- S-phase modulation by irinotecan : pilot studies in advanced solid tumors
- Creators
- N Ramnath - Roswell Park Cancer InstituteN Khushalani - United States Department of Veterans AffairsM. M Javle - Roswell Park Cancer InstituteJ Berdzik - Roswell Park Cancer InstituteP. J Creaven - Roswell Park Cancer InstituteY. M Rustum - Roswell Park Cancer InstituteK Toth - Roswell Park Cancer InstituteA. M Litwin - Roswell Park Cancer InstituteM. E Intengan - Roswell Park Cancer InstituteH. K Slocum - Roswell Park Cancer InstituteL Pendyala - Roswell Park Cancer InstituteP. F Smith - Roswell Park Cancer InstituteC. C Stewart - Roswell Park Cancer InstituteJ. L Hoffman - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.56(5), pp.447-454
- Publisher
- Springer
- DOI
- 10.1007/s00280-004-0951-6
- PMID
- 15947933
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Language
- English
- Date published
- 2005
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360154702771
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