Interim Data on Irinotecan in Relapsed/Refractory NHL Shows Substantial Activity

September 1, 2001

HOUSTON, Texas-Interim data from a trial of relatively high-dose irinotecan (Camptosar) given every 3 weeks show that the regimen can be tolerated and has substantial activity in relapsed aggressive or indolent non-Hodgkin’s lymphomas (NHL). Andreas H. Sarris, MD, PhD, associate internist in the Department of Lymphoma and Myeloma at the University of Texas M. D. Anderson Cancer Center in Houston, Texas, discussed the ongoing study. "Irinotecan weekly schedules have been associated with both early and delayed diarrhea, which is often dose limiting. Recent studies have demonstrated that 300 mg/m² IV every 21 days is active and tolerated in patients with colon cancer," Dr. Sarris said.

HOUSTON, Texas—Interim data from a trial of relatively high-dose irinotecan (Camptosar) given every 3 weeks show that the regimen can be tolerated and has substantial activity in relapsed aggressive or indolent non-Hodgkin’s lymphomas (NHL). Andreas H. Sarris, MD, PhD, associate internist in the Department of Lymphoma and Myeloma at the University of Texas M. D. Anderson Cancer Center in Houston, Texas, discussed the ongoing study. "Irinotecan weekly schedules have been associated with both early and delayed diarrhea, which is often dose limiting. Recent studies have demonstrated that 300 mg/m² IV every 21 days is active and tolerated in patients with colon cancer," Dr. Sarris said.

The phase II study Dr. Sarris described enrolled patients with relapsed or refractory aggressive NHL, relapsed indolent NHL, and relapsed or refractory mantle cell NHL. Refractory disease was defined as showing no response to initial treatment. Dr. Sarris said that refractory NHL has a particularly poor prognosis and so was separated from relapsed NHL in this study. Patients could have had no more than two prior regimens and no prior stem-cell or bone marrow transplantation.

Baseline staging was done within 3 weeks of treatment. Irinotecan was given at 300 mg/m² IV every 21 days, and patients had complete restaging every two courses. Patients with complete or partial responses after two courses received up to six courses of irinotecan.

Promising Results

Dr. Sarris reported data for 22 evaluable patients. This included 5 with indolent lymphomas, 11 with aggressive relapsed lymphomas, 3 with aggressive refractory lymphomas, and 3 with mantle cell lymphomas. Eleven of 20 patients had elevated lactate dehydrogenase (LDH) levels at baseline. Five of 19 had b2-microglobulin greater than 3.0 mg/dL at baseline. "This was not a good-prognosis population," Dr. Sarris said.

Irinotecan produced complete or partial responses in 43% of patients with indolent lymphomas, 44% of patients with relapsed aggressive lymphomas, 20% of patients with refractory aggressive lymphomas, but none of the patients with mantle cell lymphomas.

"Median duration of response was 6 months, so these were not short-lived responses but also were not a cure," Dr. Sarris said.

The main grade 3 toxicities were diarrhea (9%), neutropenic fevers (6%), neutropenia (40%, including 12% of patients with absolute neutrophil counts less than 100 cells/µL) thrombocytopenia (17%), dehydration (4%) and anorexia (2%). One toxic death occurred.

"Our conclusion so far is that patients can take this irinotecan dose safely," Dr. Sarris said. "French investigators have given even higher doses. The diarrhea and myelosuppression are manageable, and irinotecan shows promising activity in relapsed aggressive or indolent NHL."