A phase I/phase II trial of granulocyte colony-stimulating factor as bone marrow support in patients treated with vinorelbine (Navelbine): study design and goals.

Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) has recently shown great promise in the treatment of advanced breast cancer. The dose-limiting toxicity of this agent is myelosuppression; nonhematologic toxicities are typically mild and easily managed. Because of this toxicity profile, support with growth factors such as granulocyte colony-stimulating factor may allow dose escalation of vinorelbine. To investigate this issue, a two-part phase I/II clinical trial has been designed. The first portion of this study addresses the need to develop a schedule of vinorelbine administration that can be more easily integrated with growth factor support than the currently used once-weekly schedule. In this part of the study, vinorelbine will be administered on a 21-day cycle once daily for 3 consecutive days at dosage levels beginning at 15 mg/m2/d and increasing at 5 mg/m2/d until dose-limiting toxicity is reached. In the next portion of the study, granulocyte colony-stimulating factor will be given in conjunction with vinorelbine. The schedule of vinorelbine administration will again be once daily for 3 days. Vinorelbine therapy will be initiated at one dose level below the previously determined maximum tolerated dose, and the dose will be escalated at 5 mg/m2/d until the maximum tolerated dose is reached. It is hoped that this phase I/II trial will provide valuable information about both an alternative schedule of vinorelbine administration and the potential of growth factor support allowing for dose escalation of vinorelbine.