title: Phase I/II dose escalation trial of concurrent temozolomide and whole brain radiation therapy for multiple brain metastasis.
abstract: This study sought to establish the recommended phase II dose and efficacy of temozolomide (TMZ) with concurrent radiotherapy in patients with brain metastases. Patients were stratified by prior systemic therapy (≤1 vs. ≥2) and enrolled in cohorts of escalating doses of daily TMZ for 14 days (group A: 75, 95, 115, 135, or 150 mg/m(2), group B: 75, 90, 105, 120, or 135 mg/m(2)). Endpoints included safety and clinical activity. For group A (≤1 prior chemotherapy) no dose limiting toxicity was seen at 75 and 95 mg/m(2). Five of eight patients experienced dose limiting toxicities at 115 mg/m(2), thus the recommended phase II dose was 95 mg/m(2). Arm B (≥2 prior chemotherapy regimens) was closed due to poor enrollment. In the phase II portion, 17 patients in group A were treated. There were 0 patients with complete radiographic response, three with a partial response, ten remained stable, and four demonstrated early progression. The 3 and 6 month progression-free survival (PFS) rates were 41 and 18% with a median PFS time of 2.4 months. Overall survival at 3 and 6 months was 53 and 41%, respectively, with a median survival time of 4.1 months. The maximum tolerated dose of daily TMZ with concurrent WBRT was 95 mg/m(2). Despite dose escalation, outcomes did not appear to be improved in the sample treated.
authors.affiliation: Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI 48202, USA. nstom@neuro.hfh.edu
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.forename: Joe
authors.initials: J
authors.lastname: Anderson
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Doyle
authors.forename: David
authors.initials: D
authors.lastname: Croteau
authors.forename: Rita
authors.initials: R
authors.lastname: Avedissian
authors.forename: Sam
authors.initials: S
authors.lastname: Ryu
authors.forename: Lonni
authors.initials: L
authors.lastname: Schultz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide