Dose escalation of cytotoxic drugs using haematopoietic growth factors: A randomized trial to determine the magnitude of increase provided by GM-CSF

Background: The magnitude of chemotherapy dose escalation made possible by the use of recombinant haematopoietic growth factors has not been quantifie d in a randomized trial. Patients and methods: Patients with refractory or relapsing Hodgkin's disea se were randomized to receive the Dexa-BEAM regimen with escalating etoposi de doses supported by placebo or granulocyte-macrophage colony-stimulating factor (GM-CSF). Using an adaptive sampling method independently in both ar ms, the etoposide dose was escalated until the maximal tolerated dose for t he first cycle was reached. Results: Thirty patients were randomized to GM-CSF and thirty to placebo. T he etoposide dose could be escalated considerably in both treatment arms. M aximal etoposide dose for the first cycle was 1920 mg/m(2) for patients rec eiving GM-CSF and 1160 mg/m(2) for patients receiving placebo (P = 0.045 on e-sided), corresponding to a 65% higher etoposide dose and a 13% higher dos e intensity with GM-CSF. Dose-limiting events were similar in both arms, co nsisting mainly of prolonged neutropenia and consecutive infections. Treatm ent efficacy was not different in the two treatment groups. Conclusions: While GM-CSF permits a somewhat higher dose escalation than pl acebo, the increase in dose intensity provided by GM-CSF is small. The use of CSF for interval reduction rather than dose escalation is the more effec tive strategy for dose intensification.