Intravenous administration of high doses of carboplatin in multimodal treatment of high grade gliomas: a phase II study

Abstract

The object of this study is to evaluate the efficacy of a high dose of carboplatin in 20 patients operated on for high grade glioma (Group A) compared with a matched control (Group B) treated with BCNU administered after radiotherapy. The toxicity profile has been evaluated during the therapy. The survival of patients entering this study was measured in terms of months: the mean survival time was 10.45 months and the median 11.0 months in the group treated with carboplatin (8 patients are still alive); the 18-month survival rate was 10%. The mean survival time of the control group was 9.85 months and the median 10.5 months; no patients are still alive and the 18-month survival rate was 0%. On the basis of our phase II clinical study, we could conclude that i.v. administration of high-doses of carboplatin in high grade gliomas is generally well tolerated and the results are better than those of a matched control treated with 1-2 courses of BCNU (low-dose). The adjuvant treatment and the role of carboplatin in the therapy of high grade gliomas is discussed.

Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

“…Historically, patients with recurrent GBM receiving additional chemotherapy have had limited additional benefit (32). In stud-ies of patients with GBM treated by carboplatin monotherapy, PFS of 2-3 months and OS of 6-9 months were reported (21)(22)(23)(24)(25)(26). The PFS and OS results for patients experiencing minimal or no BBB disruption (grade 0/1, median PFS ¼ 2.73 months, median OS ¼ 8.64 months) align with this historical data.…”

“…The starting dose was AUC5, further adapted (AUC4 or AUC6) on the basis of clinical and biological monitoring. Carboplatin is prescribed as a third-line chemotherapy for GBM with limited efficacy; however, the clinical literature provides significant evidence that carboplatin is effective against gliomas when sufficient brain concentrations are reached, and without major brain toxicity at high doses (21)(22)(23)(24)(25)(26)(27).…”

Radiochemotherapy of Malignant Glioma in Adults

“…Having lower nephro-and ototoxicity than cisplatin, Carboplatin was tested in primary treatment settings. It showed no survival advantage over BCNU with a median survival time of 11 months versus 10.5 months after BCNU alone (+ radiotherapy) [77]. In other studies, up to 35% of objective remission rates were achieved with carboplatin despite of low blood-brain barrier penetrability [118,127], but a benefit in recurrent disease was seen only in patients with anaplastic astrocytoma and not with glioblastoma [52].…”

Plasma and cerebrospinal fluid pharmacokinetics of topotecan in a phase I trial of topotecan, tamoxifen, and carboplatin, in the treatment of recurrent or refractory brain or spinal cord tumors

“…Carboplatin and topotecan are also active agents in primary central nervous system tumors [29] and in solid tumors which commonly metastasize to the brain including breast, ovarian [30], and lung cancer [9, 31, 32]. Multani [32] administered topotecan on a daily ×5 schedule to a patient with leptomeningeal metastasis from ovarian cancer and reported the clearance of malignant cells from the CSF.…”