Irinotecan-based chemotherapy in a metastatic colorectal cancer patient under haemodialysis for chronic renal dysfunction: two cases considered.
The pharmacokinetics of irinotecan and its metabolites has been widely studied. No pharmacokinetic data, however, are available in haemodialysis patients. We report two clinical cases of severe toxicity, one of which was fatal, in two haemodialysis patients treated with irinotecan for a metastatic colorectal cancer. In case no. 1, M.S., aged 71 years, was treated with first-line FOLFIRI chemotherapy (irinotecan 180 mg/m) for local recurrence with liver metastases of a colon cancer treated with an LV5FU2 protocol as an adjuvant therapy 3 years previously. After the first cycle of irinotecan, the patient presented grade 4 diarrhoea on day 9, then a febrile grade 4 neutropenia on day 14 leading to his death on day 18. In case no. 2, M.D., aged 57 years, was treated successively by radiochemotherapy with an LV5FU2 regimen, then with four cycles of FOLFIRI (irinotecan at 125 mg/m) and finally with the cetuximab/irinotecan combination using the conventional dosage. Febrile neutropenia was observed on day 10 of the first irinotecan infusion with a dose of 180 mg/m and on day 8 of the second infusion with a lower dose of 120 mg/m. The patient's general condition progressively deteriorated with the advancement of the neoplastic disease, which led ultimately to his death. In this patient, plasma concentrations of irinotecan and its metabolite, SN-38, were measured during the course of the first FOLFIRI cycle on day 2 and on day 4, before and after dialysis sessions. The observed results suggest that, although irinotecan is partially dialysable, SN-38 is not. In conclusion, dose recommendations have to be defined in haemodialysis patients with renal dysfunction owing to the potential toxicity of irinotecan in these patients. Special care should be taken in liver metastasis cases owing to the nondialysability of SN-38.
Department of Medical Oncology, CHU Dupuytren, Limoges, France. laurence.venat@chu-limoges.fr
Laurence
L
Vénat-Bouvet
Franck
F
Saint-Marcoux
Christian
C
Lagarde
Pierre
P
Peyronnet
Valérie
V
Lebrun-Ly
Nicole
N
Tubiana-Mathieu
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000150:complications; D005472:Fluorouracil / Q000008:administration & dosage; D014890:Granulomatosis with Polyangiitis / Q000150:complications; D006470:Hemorrhage / Q000150:complications; D006801:Humans; D000077146:Irinotecan; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin