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

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/m 2 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...