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-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 microg/m(2) daily for at least 8 days. Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 microg/m(2) twice daily for 5 days before treatment. 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 disease-free by nephrectomy. (Blood. 2001;97:1942-1946)
Frederick Cancer Research and Development Center, Biological Response Modifiers Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA. janikj@mail.nih.gov
J E
JE
Janik
L L
LL
Miller
E L
EL
Korn
D
D
Stevens
B D
BD
Curti
J W
JW
Smith
M
M
Sznol
K C
KC
Conlon
W
W
Sharfman
W J
WJ
Urba
B L
BL
Gause
D L
DL
Longo
D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy*; D008545:Melanoma / Q000097:blood / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011292:Premedication; D011446:Prospective Studies; D012074:Remission Induction; D012720:Severity of Illness Index; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy*; D020521:Stroke / Q000209:etiology; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019772:Topotecan; D016178:Granulocyte-Macrophage Colony-Stimulating Factor