Early Phase II Results Show High Response Rates to Irinotecan in Relapsed/Refractory NHL

HOUSTON—Early results of an ongoing phase II trial of irinotecan in relapsed or refractory non-Hodgkin’s lymphoma (NHL) show response rates of 33% to 45% in some NHL subtypes, reported Andreas H. Sarris, MD, PhD, at the clinical investigators’ workshop. For the most responsive subtypes (indolent lymphomas, relapsed aggressive lymphomas, and possibly refractory aggressive lymphomas), patient accrual will continue, reported Dr. Sarris, Associate Professor in the Department of Lymphoma and Myeloma at the M. D. Anderson Cancer Center in Houston. The workshop was sponsored by M. D. Anderson and Pharmacia Oncology.

This phase II trial involves a new 300 mg/m² IV schedule of irinotecan given over 1 hour every 21 days. Recent studies have demonstrated this schedule was active and tolerated in patients with colon cancer. “The weekly schedules have been associated with early and delayed diarrhea, which are often dose-limiting,” Dr. Sarris said. “The French have developed an intensive loperamide (Imodium)/atropine approach for managing early diarrhea,” he added.

Patients in this trial were completely restaged every two courses, and those who had complete or partial responses after two courses were eligible to be continued for up to six courses. Doses are reduced in steps of 25 mg/m2 due to toxicity.

Responses Range up to 45%

Response rates reported by Dr. Sarris ranged from 0 for mantle cell lymphoma to 45% for relapsed aggressive NHL (see Table). This was at the cost of significant toxicity, including neutropenia with counts under 1,000/µL in 42% of cycles, platelet counts under 100,000/µL in 20% of cycles, and late grade 3/4 diarrhea in 10% of cycles.

“Irinotecan can be given at 300 mg/m² every 21 days to patients with relapsed or refractory NHL. Most patients tolerate this dose, and both early and delayed diarrhea appears manageable,” Dr. Sarris said. French researchers have given doses up to 600 mg/m².”

Irinotecan may also be active in relapsed aggressive or indolent NHL, Dr. Sarris added, noting that this study is continuing to better define the response rate and toxicity. If irinotecan continues to produce high response rates in NHL, Dr. Sarris anticipates testing it in combination with cisplatin (Platinol), cytarabine (Cytosar-U), and perhaps rituximab (Rituxan) in relapsed or recurrent NHL.