A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma

We conducted a phase II randomized trial of recombinant granculocyte-macrop hage colony-stimulating factor (GM-CSF) administered before topotecan chemo therapy to determine whether it could prevent myelosuppression and to deter mine the antitumor activity of this topoisomerase I inhibitor in 53 patient s with metastatic malignant melanoma and renal cell cancer. All patients re ceived GMCSF after topotecan at a dose of 250 mug/m(2) daily for at least 8 days, Patients randomly assigned to receive GM-CSF priming were treated wi th GM-CSF at 250 mug/m(2) twice daily for 5 days before treatment. Twenty-f ive patients were randomly assigned to receive GM-CSF priming and 28 to rec eive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutrope nia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 p atients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, with out GM-CSF priming (P =.0074). The mean duration of neutropenia was reduced by GMCSF priming: grade 3 neutropenia from 5.2 +/- 0.7 to 2.8 +/- 0.7 days (P =.0232) and grade 4 neutropenia from 2.7 +/- 0.6 to 1.1 +/- 0.4 days (P = 0.0332). The protective effects of GM-CSF extended to the second cycle o f treatment. The incidence of febrile neutropenia was also reduced. Chemoth erapy-induced anemia and thrombocytopenia were similar in both groups. One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was r endered disease-free by nephrectomy. (Blood, 2001;97: 1942-1946) (C) 2001 b y The American Society of Hematology.