Journal article
Interleukin 15 offers selective protection from irinotecan-induced intestinal toxicity in a preclinical animal model
Cancer research (Chicago, Ill.), Vol.58(15), pp.3270-3274
1998
PMID: 9699654
Abstract
Irinotecan (CPT-11) is a chemotherapeutic agent that is active in the treatment of a variety of solid tumor malignancies. Diarrhea represents the most common dose-limiting toxicity that is independent of the schedule of administration. A rat model with dose-limiting toxicity profiles that are similar to those observed in patients treated with CPT-11 was developed and used to evaluate the role of interleukin 15 (IL-15) in the modulation of the therapeutic selectivity of CPT-11 in normal rats and rats bearing advanced colorectal cancer. The maximum tolerated dose and lethal dose (LD) of CPT-11 by i.v. push daily x 3 were 150 and 200 mg/kg/day, respectively. CPT-11 at the LD induced a 93-100% incidence of severe diarrhea and an 86-100% incidence of lethality in treated animals. IL-15, a cytokine with multiple mechanisms of action, was used at a 100 or 400 microg/kg/dose with different schedules of administration (3, 8, and 11 doses, i.p.) to protect against CPT-11-induced toxicity. IL-15 offered complete and sustained selective protection against CPT-11-induced delayed diarrhea and lethality. IL-15 also moderately potentiated the antitumor activity of CPT-11 in rats bearing advanced colorectal cancer. Morphological examination of rat intestinal tissues after treatment with LD of CPT-11 revealed dramatic protection of duodenal and colonic tissue architecture by IL-15. CPT-11 alone produced serious damage to duodenal villi and colonic crypts. The results clearly demonstrated the ability of IL-15 to provide significant protection from CPT-11-induced intestinal toxicity with maintenance of antitumor activity, resulting in an increase in the therapeutic index of CPT-11. The clinical relevance of the results obtained in this model system needs to be confirmed.
Details
- Title: Subtitle
- Interleukin 15 offers selective protection from irinotecan-induced intestinal toxicity in a preclinical animal model
- Creators
- SHOUSONG Cao - Roswell Park Cancer InstituteJ. D Black - Roswell Park Cancer InstituteA. B Troutt - Immunex Corporation, Seattle, Washington 98101, United StatesY. M Rustum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.58(15), pp.3270-3274
- Publisher
- American Association for Cancer Research
- PMID
- 9699654
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 1998
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360058202771
Metrics
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