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Abstract

Metastatic brain tumors (MBT) are the most frequent complication of systemic cancer and often respond poorly to treatment. Median survival is only 16-24 weeks after conventional radiation therapy. Regional intra-arterial (IA) administration of chemotherapy results in increased tumor uptake of drug and may improve response rates and survival. Twenty-seven patients with MBT who had received prior irradiation were treated with IA carboplatin (200 mg/m2/d) and intravenous (i.v.) etoposide (100 mg/m2/d) for 2 days every 3-4 weeks. Eighteen patients (67%) had received prior systemic chemotherapy for their primary tumor. Patients ranged in age from 19 to 68 years (mean 48.1). Thirteen of 24 evaluable patients had objective responses (54.2%). There were 6 complete responses (25%), 6 partial responses (25%), 1 minor response (4.2%), 7 stable disease (32%), and 5 progressive disease (20.8%). Some patients with multifocal tumors had a mixture of responses. The median time to progression was 16.0 weeks overall and 30.0 weeks in responders (range 6-118 weeks). Overall median survival from the time of protocol initiation was 20.0 weeks. In six responders, death occurred due to systemic illness unrelated to MBT progression. Therapy was well tolerated, with predominantly hematologic toxicity. Angiographic complications were rare. Although these are preliminary results, IA carboplatin and IV etoposide is safe and well tolerated, appears to be active against brain metastases, and warrants further study.

Focused Delivery of Chemotherapy to Augment Surgical Management of Brain Tumors

“…GBM patients were treated with intra-arterial drug delivery in several clinical studies. A combination of nimustine, bevacizumab, and carboplatin with other conventional chemotherapies resulted in survival rates ranging from 20 weeks to 10 months [ 58 , 59 ].…”

Celastrol-induced degradation of FANCD2 sensitizes pediatric high-grade gliomas to the DNA-crosslinking agent carboplatin

“…Brooklyn, NY, USA) is currently being produced for clinical studies, albeit for other indications, which could contribute to the translational potential of FANCD2 inhibition in the clinic. Carboplatin, which is less toxic than cisplatin and crosses the BBB, has been used in patients for decades and the step to using this compound in HGG patients is highly feasible [10,55].…”

“…To study if depletion of the deregulated FANCD2 in pHGG cells could cause a FA-like phenotype that leads to a higher sensitivity to platina analogues, we treated primary pHGG cells with carboplatin in combination with celastrol, a blood-brain barrier (BBB) permeable compound that has been shown to cause degradation of FANCD2 via the proteasome [7,8]. In our experiments, carboplatin was chosen over other platinum chemotherapeutics because of its relatively mild neurotoxic side effects and reported ability to cross the BBB [9,10].…”

Drug Delivery Technology to the CNS in the Treatment of Brain Tumors: The Sherbrooke Experience

“…Once in position, the chemotherapy is administered via the catheter that is withdrawn at the conclusion of the procedure. The CIAC produces a paradigm of regional chemotherapy distribution within the area deserved by the vessel treated [19].…”

“…Through the first pass effect, an increase in the local plasma peak concentration of the drug produces a significantly improved AUC (the concentration of the drug according to the time) [19,20]. This consequently translates in increased local exposure of the target tissue to the therapeutic agent.…”