Hand-foot syndrome following prolonged infusion of high doses of vinorelbine

BACKGROUND. The authors reviewed the incidence of toxic skin reactions in patents with metastatic breast carcinoma (MBC) treated with vinorelbine as a continuous infusion. METHODS. A Phase I/II protocol was designed in which vinorelbine was given as an 8-mg intravenous bolus followed by a 96-hour CI of 7-14 mg/m²/day. Sixty patients were enrolled in the study: all had MBC and had received prior chemotherapy, and they had no known dermatologic disorder. RESULTS. Hand-foot syndrome (HFS) developed in 4 of the 60 patients. Patient 1 started with vinorelbine at 12 mg/m²/day. She developed typical HFS. In the second course, her dose was decreased to 11 mg/m²/day, but again she experienced HFS. In the third course, dexamethasone was added to the regimen, and no HFS was observed in the remaining six courses. Patient 2 started with a dose of 9 mg/m²/day. She received four courses without complications; but when the vinorelbine dose was escalated to 10 mg/m²/day, HFS developed. Patient 3 started with a vinorelbine dose of 14 mg/m²/day. She developed mucositis during the first two courses and HFS during the third. Patient 4 received vinorelbine at a dose of 13 mg/m²/day and developed significant HFS. All patients had complete dermatologic recovery. No toxic skin reactions were observed in 14 patients receiving vinorelbine doses of <10 mg/m²/day, whereas 4 of 46 treated at 10-14 mg/m²/day developed HFS, suggesting a relationship of dose to HFS occurrence. CONCLUSIONS. Longer infusions of vinorelbine are occasionally associated with HFS. The pathophysiology is not completely clear, but a relationship of HFS occurrence to dose is suggested. Steroids were effective as prophylaxis in one patient.