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

John E. Janik, Langdon L. Miller, Edward L. Korn, Diane Stevens, Brendan D. Curti, John W. Smith, Mario Sznol, Kevin C. Conlon, William Sharfman, Walter J. Urba, Barry L. Gause, Dan L. Longo

Research output: Contribution to journalArticle

16 Scopus citations


We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer. All patients received GM-CSF after topotecan at a dose of 250 μg/m2 daily for at least 8 days. Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 μg/m2 twice daily for 5 days before treat ment. Twenty-five patients were randomly assigned to receive GM-CSF priming and 28 to receive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutropenia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 patients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, without GM-CSF priming (P = .0074). The mean duration of neutropenia was reduced by GM-CSF 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 of treatment. The incidence of febrile neutropenia was also reduced. Chemotherapy-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 rendered diseasefree by nephrectomy.

Original languageEnglish (US)
Pages (from-to)1942-1946
Number of pages5
Issue number7
Publication statusPublished - Apr 1 2001


ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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