Irinotecan hydrochloride (CPT-11) in dialysis patients with gastrointestinal cancer.
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.
Ashizawa
Tatsuto
T
Department of Surgery, Hachioji Medical Center of Tokyo Medical University, Hachioji, Tokyo 193-0998, Japan. ashizawa@tokyo-med.ac.jp
Iwahori
Tohru
T
Yokoyama
Takayoshi
T
Kihara
Yuu
Y
Konnno
Osamu
O
Jyojima
Yoshimaro
Y
Akashi
Isao
I
Nakamura
Yuuki
Y
Hama
Kouichirou
K
Iwamoto
Hitoshi
H
Segawa
Mai
M
Takeuchi
Hironori
H
Hirano
Toshihiko
T
Nagao
Takeshi
T
D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000150:complications / Q000188:drug therapy; D006435:Renal Dialysis; D013274:Stomach Neoplasms / Q000150:complications / Q000188:drug therapy
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin