Purpose: The goal of this study was to evaluate the efficacy of the fludarabine/cyclophosphamide combination in patients with relapsed chronic lymphocytic lymphoma (CLL) and low-grade non-Hodgkin's lymphoma (NHL) and to assess the impact of adding granulocyte-macrophage colony-stimulating factor (GM-CSF) to this regimen in a randomized fashion.
Patients and methods: Thirty-four patients (CLL, n=16; low-grade NHL, n=18) were enrolled. The median number of previous treatments was 2. Patients received <or=6 cycles of fludarabine at 30 mg/m2 per day and cyclophosphamide at 300 mg/m2 per day on days 1-3 of a 28-day cycle. Patients were randomized to supportive care or to receive GM-CSF at 250 mg/m2 per day, starting 24 hours after completion of chemotherapy and continuing up to 48 hours before the next cycle. Those who had received >6 months of previous therapy with an alkylating agent or had preexisting cytopenias received a 25% dose reduction. Twenty-two patients (65%) were randomized to receive GM-CSF. Patients completed a median of 5 cycles of treatment (range, 1-6 cycles). Twenty-seven patients (80%) received >or=3 cycles of treatment and were evaluated for response.
Results: Seven patients (26%) exhibited a complete response; 6 of the 7 had low-grade NHL. Fourteen patients (52%) exhibited a partial response, and 6 patients (22%) had stable disease. Notably, 6 of the 7 patients who exhibited complete response and 9 of 14 patients with partial responses were randomized to the GM-CSF arm. The duration of response ranged from 4 months to 26 months. The toxicities were mainly hematologic. Nineteen patients (70%) experienced >or=1 episode of grade 3/4 neutropenia, but only 4 (15%) experienced febrile neutropenia; 3 of those patients were assigned to the GM-CSF arm.
Conclusions: The combination of fludarabine and cyclophosphamide is a well-tolerated and effective treatment regimen for patients with relapsed CLL and low-grade NHL. A higher percentage of complete responses were noted in patients with low-grade NHL compared with patients with CLL. Granulocyte-macrophage colony-stimulating factor did not seem to decrease the incidence of febrile neutropenia. However, the higher number of complete and partial responses noted on the GM-CSF arm is intriguing and warrants further investigation.