Phase II study of sequential topotecan and etoposide in patients with intermediate grade non-Hodgkin's lymphoma: A National Cancer Institute of Canada Clinical Trials Group Study

Michael Crump, Stephen Couban, Ralph Meyer, Leona Rudinskas, Brent Zanke, Stefan Gluck, Andrew Maksymiuk, Paul Hoskins, Sarah Matthews, Elizabeth Eisenhauer

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Preliminary results indicate that inhibitors of the nuclear enzyme topoisomerase (topo) I, such as topotecan, may be active in non-Hodgkin's lymphoma (NHL). Pre-clinical studies have shown sequential administration of a topo I and II inhibitor has supra-additive anti-tumor effects in some model systems, and that greater cytotoxicity occurs if the topo I inhibitor is given first. We enrolled 22 eligible patients with relapsed or refractory intermediate grade NHL in a phase II study of sequential administration of topotecan 1.25 mg/m2 days 1-5 and etoposide 50 mg po b.i.d. days 6-12, every 28 days without G-CSF. Most patients had diffuse large B-cell lymphoma and all had received only one prior regimen (CHOP, 20 patients, or equivalent, 2 patients). Patients with stable or responding disease were allowed to proceed to high-dose therapy and autologous stem-cell transplant after 2 cycles of therapy. The 22 patients received a total of 62 cycles of topotecan + etoposide (median 2, range 1-6), and 4/22 completed all six planned cycles. Hematologic toxicity was significant and resulted in incomplete etoposide dosing in half of all cycles in 16/22 patients. Nineteen of twenty-two patients had grade 3/4 neutropenia, 12 had grade 3/4 thrombocytopenia, and 6 grade 3/4 anemia. Eleven patients had at least one episode of febrile neutropenia or had documented infection. Non-hematologic toxicity was mild. Four patients had a partial response (PR) (18.2%), nine had stable disease and seven progressed; three patients with stable disease went on to ABMT. The combination of topotecan and etoposide as given in this study has modest activity in relapsed/refractory aggressive histology NHL, and produces marked myelosuppression. Other doses and schedules combining topo I and II inhibitors, or topo I inhibitors with alkylating agents, should be explored with the addition of hematopoietic growth factors in this patient population.

Original languageEnglish (US)
Pages (from-to)1581-1587
Number of pages7
JournalLeukemia and Lymphoma
Volume43
Issue number8
DOIs
StatePublished - Jan 1 2002

Keywords

  • Etoposide
  • Non-Hodgkin's lymphoma
  • Relapsed
  • Topoisomerase I
  • Topotecan

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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