REDUCTION BY GRANULOCYTE-COLONY-STIMULATING FACTOR OF FEVER AND NEUTROPENIA INDUCED BY CHEMOTHERAPY IN PATIENTS WITH SMALL-CELL LUNG-CANCER

Background. Neutropenia and infection are major dose-limiting side eff ects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce ch emotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical im plications. Methods. Patients with small-cell lung cancer were enrolle d in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, < 1. 0 X 10(9) per liter, with a temperature greater than or equal to 38.2 degrees C) resulting from up to six cycles of chemotherapy with cycle- phosphamide, doxorubicin, and etoposide. The patients were randomly as signed to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. Results. The s afety of the study treatment could be evaluated in 207 of the 211 pati ents assigned to either drug, and its efficacy in 199. At least one ep isode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P < 0.001). Ove r all cycles of chemotherapy, the median duration of grade IV neutrope nia (absolute neutrophil count, < 0.5 X 10(9) per liter) was six days with placebo as compared with one day with G-CSF. During cycles of bli nded treatment, the number of days of treatment with intravenous antib iotics, the number of days of hospitalization, and the incidence of co nfirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. Conclusio ns. The use of G-CSF as an adjunct to chemotherapy in patients with sm all-cell cancer of the lung was well tolerated and led to reductions i n the incidence of fever with neutropenia and culture-confirmed infect ions; in the incidence, duration, and severity of grade IV neutropenia ; and in the total number of days of treatment with intravenous antibi otics and days of hospitalization.