A SINGLE-BLIND, RANDOMIZED, VEHICLE-CONTROLLED DOSE-FINDING STUDY OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (LENOGRASTIM) IN PATIENTS UNDERGOING CHEMOTHERAPY FOR SOLID CANCERS AND LYMPHOMA

This study evaluated the effect of glycosylated recombinant human gran ulocyte colony-stimulating factor (rHuG-CSF; lenograstim) on neutrophi l granulocyte counts and on cells of other haematopoietic lineages in 66 patients with solid cancer or lymphoma who received myelosuppressiv e chemotherapy. Beginning 1 day after completion of chemotherapy, pati ents received lenograstim (at dosages of 0.5, 2, 5 or 10 mu g/kg) or v ehicle subcutaneously once daily for 14 consecutive days. Compared wit h vehicle, lenograstim significantly accelerated neutrophil recovery a fter chemotherapy in a dose-dependent manner. Mean neutrophil counts r ecovered to >1.0 x 10(9) cells/l by day 13 in the vehicle group compar ed with days 11, 10, 8 and 7 in the 0.5, 2, 5 and 10 mu g/kg lenograst im groups, respectively. Doses of 0.5 and 2 mu g/kg of lenograstim had a significant effect on the duration of neutropenia (<1.0 x 10(9) cel ls/l), the area under the absolute neutrophil count (ANC) curve and th e time to ANC nadir. The dose of 5 mu g/kg additionally decreased the total area of neutropenia and gave the narrowest range of values for a ll neutrophil parameters, while the 10 mu g/kg dose brought no added b enefit. A dose-response effect of lenograstim on time to neutrophil re covery was observed both for patients who received chemotherapy on a s ingle day (n = 35) and for those who received chemotherapy over severa l days (n = 29). Based on these findings, a dose of 5 mu g/kg/day was chosen for further trials.