title: Safety and feasibility of motexafin gadolinium administration with whole brain radiation therapy and stereotactic radiosurgery boost in the treatment of ≤ 6 brain metastases: a multi-institutional phase II trial.
abstract: To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ≤ 6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ≥ 4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ≥ 3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost.
authors.affiliation: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, K4/B100, Madison, WI 53792, USA. mchaffie@humonc.wisc.edu
authors.forename: Derek R
authors.initials: DR
authors.lastname: McHaffie
authors.forename: Pierre
authors.initials: P
authors.lastname: Chabot
authors.forename: Anne
authors.initials: A
authors.lastname: Dagnault
authors.forename: John H
authors.initials: JH
authors.lastname: Suh
authors.forename: Marie-Andrée
authors.initials: MA
authors.lastname: Fortin
authors.forename: Eric
authors.initials: E
authors.lastname: Chang
authors.forename: Robert
authors.initials: R
authors.lastname: Timmerman
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.forename: John
authors.initials: J
authors.lastname: Grecula
authors.forename: Abdenour
authors.initials: A
authors.lastname: Nabid
authors.forename: Chris
authors.initials: C
authors.lastname: Schultz
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Gaspar
authors.forename: David
authors.initials: D
authors.lastname: Brachman
authors.forename: Tarak
authors.initials: T
authors.lastname: Mody
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000401:mortality* / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009369:Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D016634:Radiosurgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008665:Metalloporphyrins; C437683:motexafin gadolinium