Extended-schedule dose-dense temozolomide in refractory gliomas

• Published in: Journal of neuro-oncology Vol. 96; no. 3; pp. 417 - 422
• Main Authors: Berrocal, A., Perez Segura, P., Gil, M., Balaña, C., Garcia Lopez, J., Yaya, R., Rodríguez, J., Reynes, G., Gallego, O., Iglesias, L.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2010; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic Agents, Alkylating - therapeutic use; Brain Neoplasms - drug therapy; Brain Neoplasms - mortality; Clinical Study - Patient Study; Dacarbazine - analogs & derivatives; Dacarbazine - therapeutic use; Drug Administration Schedule; Drug Delivery Systems; Female; Glioma - drug therapy; Glioma - mortality; Humans; Kaplan-Meier Estimate; Male; Medicine; Medicine & Public Health; Middle Aged; Neurology; Oncology; Temozolomide; Treatment Outcome; Young Adult; Refractory; Malignant glioma; Activity; Temozolomide
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-009-9980-7

This multicenter phase II study conducted by the Spanish Neuro-Oncology Group evaluated the activity of an extended, dose-dense temozolomide regimen in patients with temozolomide-refractory malignant glioma. Adult patients (at least 18 years of age) with WHO grade III or IV glioma and a Karnofsky Performance Status of 60 or higher were treated with temozolomide (85 mg/m 2 /day) for 21 consecutive days every 28-day cycle until disease progression or unacceptable toxicity. All patients had developed progressive disease either during or less than 3 months after completing previous temozolomide treatment. Forty-seven patients were treated with a median of 2 (range, 1–13) cycles of temozolomide. Before study entry, patients had received a median of 6 cycles of temozolomide: 39 (83%) as part of initial therapy and 23 (49%) as second-line therapy. Three patients (6.4%) had a partial response with durations of 8.0, 3.5, and 3.2 months; 15 patients (31.9%) had stable disease with a median duration of 2.1 months, including 2 patients with stable disease (SD) for greater than 6 months (14 and 16 months). Median time to progression was 2 months, and median overall survival from study entry was 5.1 months. The 6-month progression-free survival rate was 16.7%. The most common hematologic toxicities were lymphopenia, thrombocytopenia, and leukopenia. Lymphopenia occurred in 83% of patients and was grade 3 in 28%, but no opportunistic infections occurred. In conclusion, this extended dose-dense schedule of temozolomide appears to have modest activity in patients refractory to previous treatment with temozolomide and is associated with manageable toxicity.