Treatment > Topotecan

Abstract

Response of relapsed or refractory primary central nervous system lymphoma (PCNSL) to topotecan

A. Korfel, L. Fischer, E. Thiel

Klinikum Benjamin Franklin, Berlin, Germany

Up to 30% of immunocompetent patients with PCNSL are primarly refractory to treatment and up to 60% relapse after achieving remission.
Median survival of these patients is 2 months without treatment.
No standard salvage therapy for PCNSL could be established thus far.
The topoisomerase I inhibitor topotecan has been shown to be effective in relapsed or refractory non-Hodgkin's lymphomas.
Moreover, it is able to cross the intact blood-brain barrier.
Based on these properties, we examined the effectivity of topotecan for second-line treatment of PCNSL.
Fiveteen patients with non-AIDS-related PCNSL (7 with refractory and 8 with relapsed disease) were treated with 1.5 mg/m2/d topotecan i.v. d1-5 3-weekly.
All but one were pretreated with up to 3 high-dose methotrexate based chemotherapy regimens and 4 patients were pretreated with whole-brain irradiation (WBI).
Six patients (1 with refractory and 5 with relapsed disease) responded (3 CR, 3 PR) for an overall response rate of 40%.
One patient had stabile disease, 6 patients progressed, and one patient was not evaluable for response.
Median overall survival after starting topotecan was 6 months (range 2-30+ months).
Six patients are free of disease 6 to 30 months after diagnosis of relapse.
Four of these patients received WBI after topotecan, and in 2 no further therapy was administered.
Topotecan was generally well tolerated with hematotoxicity being the most common adverse event.
Neutropenic fever occurred in 2 patients.
Clinically relevant late neurotoxicity was observed in 2 patients.
Single-agent topotecan is an effective second-line therapy in PCNSL and warrants further investigation.

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