Pre-irradiation semi-intensive chemotherapy with carboplatin and cyclophosphamide in malignant glioma: a phase II study.
ABSTRACT We undertook a phase II trial in 17 patients with malignant glioma and large measurable disease to assess response rate and survival with pre-irradiation chemotherapy, using higher doses than standard, trying to improve the outcome. Patients characteristics were: male/female 10/7, age 49 (range 23-59), median Karnofsky index 90% (range 70-100), glioblastoma multiforme/anaplastic astrocytoma 14/3. Treatment consisted of 2 cycles of carboplatin 200 mg/m(2) days 1-3 (or AUC x 8, total dose) plus cyclophosphamide 1000 mg/m(2) days 1-3. One partial response (6.5%) and two stabilizations (13.5%) were observed after pre-irradiation chemotherapy. Twelve out of 15 patients (80%) progressed after chemotherapy. Median survival time was 7.6 months and the survival at 1 year was 33%. Main toxicity was hematologic in the first cycle: neutropenia grade 4 in 100%; thrombocytopenia grade 4 in 73% and grade 3 in 27%; anemia grade 3 in 7%; in the second cycle: neutropenia and thrombocytopenia grade 4 in 100% and anemia grade 3 in 50%). No toxic death was related to treatment. This regimen showed limited activity in malignant glioma with large residual disease after surgery or biopsy.
Article: Carboplatin and oral cyclophosphamide combination after temozolomide failure in malignant gliomas.[show abstract] [hide abstract]
ABSTRACT: Temozolomide is a novel cytotoxic agent for malignant gliomas. However, treatment failure occurs approximately in half of patients, and the optimal regimen in this setting has yet to be defined. In the present study, we assessed retrospectively the efficacy and toxicity of the combination of carboplatin and oral cyclophosphamide in temozolomide-resistant patients. We evaluated the medical records of 30 patients with malignant gliomas. After failure of temozolomide therapy, patients were treated with a combination of carboplatin and oral cyclophosphamide. Treatment consisted of intravenous carboplatin AUC 6 (based on the Calvert Formula) on day 1 and oral cyclophosphamide 75 mg/m2 daily on days 1 to 14, followed by 14 days of rest, with the treatment repeated every 4 weeks. All patients were evaluated for response and toxicity. The objective response rate was 30%, including 9 partial responses. Median time to disease progression and median overall survival was 7 months and 8 months, respectively. Clinically responsive patients had statistically significant longer progression-free survival and overall survival than unresponsive patients. Hematological side effects were commonly observed toxicities, with neutropenia the most frequent. Our data suggest that carboplatin and oral cyclophosphamide therapy is a convenient regimen after failure of temozolomide therapy in patients with malignant gliomas because of its activity, feasibility and tolerability. Further prospective studies are needed in this setting.Tumori 94(5):674-80. · 0.86 Impact Factor