Drug Interaction Report

MONITOR CLOSELY: Topotecan combined with a platinum agent may produce synergistic cytotoxicity against some germ cell cancers. However, myelosuppression may also be more severe. In a reported study where patients were given cisplatin 50 mg/m2 and topotecan 1.25 mg/m2/day for 5 days, one of three patients had severe neutropenia for 12 days and a second patient died with neutropenic sepsis. The interaction appears to be sequence-dependent. Specifically, coadministration of a platinum agent on day 1 of topotecan dosing required lower dosages of each agent compared to coadministration on day 5 of the topotecan dosing schedule.

MANAGEMENT: There are currently insufficient data to recommend a safe and effective regimen for topotecan in combination with a platinum agent. Clinicians should recognize the potential risk for severe neutropenia if these agents are used together, and bone marrow function must be closely monitored. Lower dosages of each agent may be required.