A Phase II Study of Recombinant Granulocyte Macrophage Colony Stimulating Factor in Patients with Non-Hodgkin's Lymphoma

Abstract

Myelosuppression is often the major limiting factor that prevents timely administration of cytotoxic chemotherapeutic agents, particularly in chemoresponsive malignancies. A study was designed to assess the role of GM-CSF in preventing myelosuppression in patients with intermediate-grade non-Hodgkin's lymphoma receiving combination chemotherapy (Cyclophosphamide, Vincristine, Prednisone and Epirubicin or Mitozantrone, ± Bleomycin). A total of 24 patients were entered and data collated from 20 of them are amenable to analysis.

All patients received the first chemotherapy cycle without GM-CSF and the second with GM-CSF (250 mg/m² subcutaneously twice daily for 5 days commencing on the 5th day following chemotherapy). By entering only those patients who had suffered myelosuppression following chemotherapy, an internal control was established. GM-CSF administration significantly reduced the degree of neutropenia and leucopenia. The mean nadir white blood cell (WBC) and absolute neutrophil counts (ANC) were 2.88 × 10⁹/L and 0.97 × 10⁹/L in cycle 1 as compared to 5.95 × 10⁹/L and 2.92 × 10⁹/L respectively, in cycle 2 (p = 0.05 and 0.02, respectively). Eight patients (40%) had febrile neutropenias and 13 patients (65%) experienced a treatment delay by a median of 8 days during cycle 1. Six patients (30%) had febrile neutropenias and 2 patients (10%) had a treatment delay of 3 days during cycle 2. Reversible toxicity was seen in the majority of patients: bone pains (60%), skin rashes (35%), arthralgias (25%), and altered taste sensation (10%). No patient developed the capillary leak syndrome. This study demonstrates the efficacy of GM-CSF in preventing chemotherapy-induced myelosuppression.

Key Words:

• GM-CSF
• non-Hodgkin's
• lymphoma
• phase II study