title: 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.
authors.affiliation: Radiation Oncology, New York Methodist Hospital, Weill Medical College of Cornell University, 506 6th Street, Brooklyn, NY 11215, USA. hashamalla@aol.com
authors.forename: H
authors.initials: H
authors.lastname: Ashamalla
authors.forename: B
authors.initials: B
authors.lastname: Zaki
authors.forename: B
authors.initials: B
authors.lastname: Mokhtar
authors.forename: L
authors.initials: L
authors.lastname: Lewis
authors.forename: A
authors.initials: A
authors.lastname: Lavaf
authors.forename: H
authors.initials: H
authors.lastname: Nasr
authors.forename: F
authors.initials: F
authors.lastname: Colella
authors.forename: D
authors.initials: D
authors.lastname: Dosik
authors.forename: M
authors.initials: M
authors.lastname: Krishnamurthy
authors.forename: N
authors.initials: N
authors.lastname: Saad
authors.forename: A
authors.initials: A
authors.lastname: Guriguis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000097:blood; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010672:Phenytoin / Q000097:blood; D016634:Radiosurgery / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D000972:Antineoplastic Agents, Phytogenic; D010672:Phenytoin; D017239:Paclitaxel