Irinotecan hydrochloride (CPT-11) in dialysis patients with gastrointestinal cancer.

Abstract

We investigated changes in drug disposition and toxicities with CPT-11 in 15 dialysis patients with gastrointestinal cancers to clarify whether CPT-11 could be administered safely in such patients. For comparison, the same parameters were also investigated in 10 cancer patients not undergoing dialysis. Items investigated included (1) plasma concentrations of SN-38, SN-38G and CPT-11 at 0, 1, 12, 24, 36, 48 and 72 h after administration, together with a comparison of mean AUC values for 3 dose levels of CPT-11 (50, 60 and 70 mg/m2) in dialysis patients and controls; and (2) occurrence of adverse events. Several findings emerged from this study: (1) No significant difference was observed in the AUC for SN-38 or CPT-11 between the dialysis and control groups; (2) The AUC for SN-38G at each dose was significantly higher in dialysis patients; and (3) Grade 1-4 leucopenia was observed in 11 of the dialysis patients. One patient developed grade 4 leucopenia and died due to sepsis. Anorexia, diarrhea, nausea, alopecia and interstitial pneumonia occurred in 6 dialysis patients. We found changes in drug dispositions of CPT-11, SN-38 and SN-38G in dialysis patients, suggesting that hepatic excretion, especially that of SN-38G, was increased. No significant difference in occurrence of adverse events was observed between the 2 groups. This indicates that CPT-11 can be administered safely in patients on dialysis.

• Authors: Tatsuto Ashizawa, Tohru Iwahori, Takayoshi Yokoyama, Yuu Kihara, Osamu Konnno, Yoshimaro Jyojima, Isao Akashi, Yuuki Nakamura, Kouichirou Hama, Hitoshi Iwamoto, Mai Segawa, Hironori Takeuchi, Toshihiko Hirano, Takeshi Nagao
• Journal: Acta medica Okayama (Acta Med Okayama) Vol. 64 Issue 1 Pg. 19-26 (Feb 2010) ISSN: 0386-300X [Print] Japan
• PMID: 20200580 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Irinotecan
• Camptothecin

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, blood)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, blood)
• Colorectal Neoplasms (complications, drug therapy)
• Female
• Gastrointestinal Neoplasms (complications, drug therapy)
• Humans
• Irinotecan
• Kidney Failure, Chronic (complications, therapy)
• Leukopenia (chemically induced)
• Male
• Middle Aged
• Rectal Neoplasms (complications, drug therapy)
• Renal Dialysis
• Stomach Neoplasms (complications, drug therapy)