Low-dose versus standard-dose lenograstim prophylaxis after chemotherapy: A randomized, crossover comparison

Purpose: Granulocyte colony-stimulating factor (G-CSF) administered prophyl actically after chemotherapy reduces the duration and severity of neutropen ia. This randomized crossover study was designed to assess whether a lower dose of G-CSF is as effective as a standard dose of 5 mu g/kg daily. Patients and Methods: Patients who received standard-dose chemotherapy regi mens expected to cause neutropenia received G-CSF (lenograstim) that starte d the day after chemotherapy for 14 days or until the absolute neutrophil c ount (ANC) recovered to greater than 10 x 10(9)/L. The lenograstim dose was randomly allocated to be 2 or 5 mu g/kg daily in the first cycle of chemot herapy and crossed over to the alternate dose for the second cycle. The stu dy was designed to accrue 40 assessable patients to provide a power of 80% to detect a difference in duration of neutropenia of 1 day. Fifty-two patie nts were randomized to treatment and 43 patients completed two cycles of id entical chemotherapy. Results: There was little neutropenia irrespective of the dose used. Twenty -three patients (53%) had no grade III or IV neutropenia and 30 patients (7 0%) had no grade IV neutropenia. Crossover trial methodology wets used to a ssess the difference in outcome caused by the lower dose compared with the standard dose (estimated treatment effect). There was no significant differ ence in the measures of neutropenia, hospitalization, or other clinical out comes. The 95% confidence interval (one-sided) for the additional duration of neutropenia caused by the lower dose of lenograstim was 0.43 days or les s for grade III or IV neutropenia and 0.34 days or less for grade IV neutro penia. Conclusion: Lenograstim 2 mu g/kg provides similar protection to 5 mu g/kg against neutropenia that complicates standard-dose chemotherapy. The use of a lower dose has important implications for the cost-effectiveness of prop hylactic G-CSF therapy. (C) 1998 by American Society of Clinical Oncology.