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Purpose: Feasibility, antitumor activity and toxicity of accelerated hyperfractionated radiation therapy (Acc Hfx RT) and concurrent carboplatin/etoposide (CBDCA/VP 16) chemotherapy were investigated in patients with malignant glioma., Material and Methods: Seventy-nine patients with either glioblastoma multiforme (GBM) (n = 61) or anaplastic astrocytome (AA) (n = 18) entered into a phase II study on the use of Acc Hfx RT with 60 Gy in 40 fractions in 20 treatment days over 4 weeks and concurrent CBDCA, 200 mg/m2, and VP 16, 200 mg/m2, both given once weekly during the RT course., Results: The median survival time for all 79 patients was 14 months (11 and 44 months for GBM and AA patients, respectively), while the 2- and 4-year survival was respectively 33% and 11% for all patients, 13% and 1.6% for GBM patients, and 100% and 44% for AA patients (p < 0.0001). The median time to progression for all patients was 12 months (9 and 40 months for GBM and AA, respectively), while the 2- and 4-year progression-free survival (PFS) was respectively 28% and 10% (all patients), 10% and 1.7% (GBM) and 89% and 39% (AA) (p < 0.0001). Multivariate analysis showed that age, performance status, and preoperative size of tumor influenced survival in GBM. Only 5 (6%) patients experienced grade 3 leukopenia and 6 (8%) patients experienced grade 3 thrombocytopenia. No late RT-induced toxicity was observed to date., Conclusions: Although Acc Hfx RT/CBDCA + VP 16 was feasible and little toxic, it failed to improve survival/progression-free survival over that obtained with other currently used regimens. These results do not justify the investigation of this regimen in a phase III trial.

Purpose: To evaluate efficacy of short-course radiotherapy (RT) in elderly (> or = 60 years) and frail [Karnofsky performance status (KPS) 50-70] patients with glioblastoma multiforme (GBM)., Materials and Methods: Between January 1987 and June 1993, a total of 47 elderly and frail patients with histological diagnosis of GBM entered into a phase II study. RT alone was administered with tumor dose of 45 Gy in 15 daily fractions in 15 treatment days in 3 weeks to a target volume described as tumor visible on CT scan and a 2-cm margin., Results: Forty-four patients were evaluable for this analysis. There were 15 (34%) CR and 11 (25%) PR, making the overall response rate of 60%. Median duration of response was 9 months (range, 2-36 months). Improvement in pretreatment performance status was observed in 20/44 (45%) patients, 5 of which improved their KPS for 20%. Median survival time is 9 months, and 1-4 year survival rates are 39%, 6.8%, 4.5%, and 0, respectively, while median time to tumor progression is 8 months, and 1-4 year progression-free survival rates are 30%, 4.5%, 4.5%, and 0, respectively. Females did significantly better than males, patients with KPS 60-70 did significantly better than those with KPS 50, patients having tumors 4-5 cm did significantly better than those with tumors 6-8 cm as well as did those with more radical surgery when compared to those with biopsy only. On multivariate analysis, only tumor size and extent of surgery were found to independently influence survival. Acute toxicity was generally assessed as mild. One of the 12 (8%) autopsied patients had RT-induced brain necrosis., Conclusion: This shortened RT appears to be an effective tool in palliation of elderly and frail patients with GBM. Further studies with more patients are needed before testing it against more aggressive treatment approaches in this patient population.

Between 1988 and 1991, eighty-six patients with glioblastoma multiforme were evaluated in order to define the influence of extent of surgery and tumor location on treatment outcome. Patients underwent surgery followed by postoperative hyperfractionated radiotherapy and chemotherapy delivered according to one of two consecutive protocols. Surgery consisted of biopsy in 25 (29%) patients and subtotal or gross total tumor resection in 61 (71%) patients. Frontally located tumors were noted in 26 (30%) patients and other tumor locations were noted in 60 (70%) patients. Patients having more radical surgery had longer median survival time (MST) and higher 1- and 2-year survival rates than those with biopsy only (56 vs 29 weeks, respectively; 62% and 23% vs 16% and 0%, respectively; p = 0.00000). Patients having frontally located tumors had longer MST and higher 1- and 2-year survival rates than those with other tumor locations (101 vs 47 weeks, respectively; 76% and 44% vs 37% and 2.5%, respectively; p = 0.00001). Multivariate analysis confirmed that extent of surgery and tumor location were independent prognostic factors in patients with glioblastoma multiforme. Regarding progression-free survival, patients having more radical surgery had longer median time to tumor progression (MTP) than those with biopsy only (33 weeks vs 21 weeks, respectively). Also, progression-free survival at 1 year was higher in radically resected group than in biopsy only group (20% vs 0%, respectively; p = 0.00000). Patients with frontally located tumors had longer MTP (42 weeks) and higher progression-free survival at 1 year (42%) than those with other tumor location (28 weeks and 1.7%, respectively; p = 0.00002).(ABSTRACT TRUNCATED AT 250 WORDS)