A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases

Purpose: To investigate the efficacy and safety of the combination of vinorelbine and intensive temozolomide for recurrent or progressive brain metastases from solid tumors. Methods; Patients ≥18 years of age and with Karnofsky performance scale (KPS) ≥60, adequate organ function and progressive or recurrent brain metastases were eligible. This was a phase II trial with 28-day cycles using temozolomide (150 mg/m², days 1-7 and 15-21) and vinorelbine 25 or 30 mg/m²on days one and eight. The primary endpoint was objective radiographic response. Results: Thirty-eight patients (15 men, 23 women) with a median age of 57 years (range, 39-75) and median KPS of 80 were enrolled. The primary tumor sites were lung (n = 20), breast (n = 11), colorectal (n = 2), kidney (n = 2), bladder (n = 1), endometrium (n = 1), head and neck (n = 1). Prior therapies included chemotherapy (97%), whole-brain radiation therapy (79%), brain metastasis resection (53%) and stereotatic radiosurgery (47%). Objective radiographic response rate was 5% (one complete response and one minor response); five patients had stable disease, 29 progressive disease and two patients were not evaluable. Twenty-nine patients (76%) have died and the median follow-up of survivors was six months. Median progression-free and overall survivals were 1.9 and 5 months, respectively. Grade 3/4 toxicities were mainly hematological and two patients discontinued the study due to myelosuppression. Conclusions: In this heavily pretreated population of patients with brain metastases, adding vinorelbine and increasing the intensity of temozolomide do not improve response rates compared to previous studies with single-agent temozolomide at standard doses.