Fractionated Stereotactic Radiotherapy Boost and Weekly Paclitaxel in Malignant Gliomas Clinical and Pharmacokinetics Results

Abstract

Management of Malignant Gliomas continues to be a challenge. We prospectively studied the role of adding weekly Paclitaxel to Fractionated Stereotactic Radiation Therapy (FSRT) in the treatment of Malignant Gliomas. Twenty-three Glioblastoma Multiforme and two Anaplastic Astrocytoma were studied. Patients received 46 Gy at 2 Gy/fraction followed by a boost utilizing FSRT at a fraction of 2.5 Gy for 8 fractions. Paclitaxel is delivered concomitantly at 150 mg/m(2) weekly for six cycles. Eighteen patients had pharmacokinetic assays of Paclitaxel levels. All patients were followed until death or for a maximum of 36 months. The overall survival of the whole group was 14 months. The median survival for RPA prognostic classes III, IV, V, and VI were 20, 14, 12, and 11 months. Higher survival (14 months) was noted in the subtherapeutic phenytoin level group compared to 10 months in the therapeutic group (P=0.271). No grade 4 CTCAE (version 3.0) toxicities were observed. Enhanced survival was demonstrated with gross tumor resection (20.8 months), KPS > or =80 (18.7 months) and age < or =60 years (27 months) as compared to subtotal resection or biopsy (12.1 months, P< 0.005), KPS < or =70 (10.8 months, P=0. 005) and older age > 60 (10.46 months, P=0.006), respectively. Our study suggests that: i) the use of weekly Paclitaxel and FSRT in Gliomas is well tolerated with a survival of 14 months; ii) the regimen resulted in improvement of survival of RPA classes IV, V, VI; and iii) the use of FSRT boost may be studied with other chemotherapeutic agents to see if superior results can be attained.

Mesenchymal stem cells loaded with paclitaxel&ndash;poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

“…It has exhibited potent cytotoxicity against malignant gliomas by intratumoral convection-enhanced delivery in Phase I/II clinical studies and combination therapy with topotecan and filgrastim or fractionated stereotactic radiotherapy in clinical trials. [24][25][26] Recent in vitro studies have shown that after MSC uptake, the active form of Ptx can be released from MSC Ptx via the Pgp system or via membrane microvesicles, giving MSCs their strong antitumor activity. 14,27 However, cell dysfunction after Ptx priming, mechanical filtration of circulating MSCs, and the bloodbrain barrier make convenient systematic injection methods challenging, including injections into the tail vein, femoral vein, and carotid artery.…”

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs

“…Several studies have investigated the concomitant delivery of paclitaxel with radiation in patients with GBM. Ashamalla et al [62] observed that the concomitant administration of paclitaxel with radiotherapy to GBM patients was well tolerated and resulted in an overall survival of 14 months. Julka et al [63] also reported on a similar treatment approach in GBM patients and showed that the overall survival rate at 1 year was 70% with a combined paclitaxel/radiotherapy treatment approach.…”

Survivin specific siRNA associated with paclitaxel synergistically inhibits glioma U-87MG cells proliferation and related mechanism

“…The most common side effects were severe acute hypersensitivity, anemia, neutropenia, thrombocytopenia, leucopenia, arthralgia, peripheral neuropathy, alopecia, mucositis, nausea/vomiting and diarrhea. PTX can cause shortness of breath, hypotension, angioedema, urticaria, flushing rash et al Considering its serious side reaction it is very important to reduce PTX dosage but maintain the same treatment effect (11). So we consider that PTX should combine with other treatments such as gene therapy.…”