Phase II study of docetaxel and vinorelbine plus GM-CSF in malignant melanoma
18017 Background: Patients having locoregional or metastatic melanoma have a poor prognosis, with 50% to 10% of patients dying from the disease within 5 years. Current chemotherapy regimens offer limited benefits to these patients and more effective and less toxic treatments are needed. Methods: We developed a phase II clinical trial to evaluate the activity of an every two week schedule of docetaxel (40mg/m2, d1), vinorelbine (30 mg/m2, d1) IV and sargramostim (GMCSF, 250 ug/m2 sq d2–11). This regimen was developed based on preclinical synergistic activity of paclitaxel plus vinorelbine (Neale et al. Melanoma Res 11:601, 2001), and evidence that the docetaxel plus vinorelbine combination can be given safely to lung cancer patients (Sanchez et al. Lung Ca 38:309, 2002). Sargramostim was included based on preliminary clinical data that it delays time to progression in stage IV melanoma patients resected for cure (Spitler, JCO 18:1614, 2000). We report here an interim analysis for the initial 21 patients with stage IV melanoma treated in first or second line. Results: The primary endpoint was time to progression. Grade III/IV toxicities included anemia (12.5%) and neutropenia (5%), with one patient requiring 25% dose reduction. To date, median time to progression (TTP) is 7 months, with 30% of cases showing greater than 8 months TTP. Conclusions: This result compares favorably with biochemotherapy, which has a median TTP of 5 months and overall survival of 8.4 months (Atkins Proc ASCO 22:708. 2003), while being significantly less toxic. Based on these favorable findings, we are continuing to accrue patients to this trial. [Table: see text]