Re: Irinotecan-Related Cholinergic Syndrome Induced by Coadministration of Oxaliplatin

Extract

Valencak et al. ( 1 ) have recently reported a case of cholinergic syndrome in a phase II study of oxaliplatin combined with CPT-11.

The patient presented the adverse event when CPT-11 was given 1 hour after oxaliplatin, while no side effects were observed when CPT-11 was given 1 day after oxaliplatin. This anecdotal episode with two positive rechallenges led the authors to suggest that there is a potential interaction between the two drugs.

The CPT-11/oxaliplatin combination has been explored in phase I studies in France, and preliminary results have demonstrated it to be a safe regimen and active in patients with 5-fluorouracilresistant colorectal cancer. More than 50 patients have been treated with over 250 cycles of this therapy given every 2 or 3 weeks ( 2 , 3 ). We have not seen any evidence of enhanced incidence or severity of CPT-11-related toxicity. No pharmacokinetic interaction between the two agents has been detected ( 4 ). The only finding concerning increased toxicity was the observation of severe CPT-11-related toxicity (neutropenia and/or diarrhea) in two patients with Gilbert's syndrome ( 5 , 6 ). With a strong pharmacologic rationale, we considered that this phenomenon was attributable to impaired metabolism of CPT-11's active metabolite, SN-38, in patients with deficient hepatic glucuronidating activity.