title: Efficacy and patient-reported outcomes with dose-intense temozolomide in patients with newly diagnosed pure and mixed anaplastic oligodendroglioma: a phase II multicenter study.
abstract: Standard initial therapy for patients with pure and mixed anaplastic oligodendrogliomas (AO/MAO) includes chemotherapy and radiation therapy. Anaplastic oligodendrogliomas with 1p/19q co-deletion are more responsive to chemotherapy. There is concern for potential long-term CNS toxicity of radiation. Hence an approach using chemotherapy initially and reserving radiation for progressive disease is attractive. This multicenter phase II trial included patients with newly diagnosed AO/MAO with central pathology review and 1p/19q assay. Temozolomide was given 150 mg/m(2) days 1-7 and 15-21, every 28 days for 8 cycles. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rate, overall survival (OS), treatment toxicity and health-related quality of life (HRQL). Data from 62 patients enrolled between December 2001 and April 2007 at seven centers were analyzed. Among patients with measurable disease, 8 % achieved complete remission, 56 % had stable disease and 36 % had progression. The median PFS and OS were 27.2 months (95 % CI 11.9-36.3) and 105.8 months (95 % CI 51.5-N/A), respectively. Both 1p loss and 1p/19q co-deletion were positive prognostic factors for PFS (p < 0.001) and OS (p < 0.001); and there was some suggestion that 1p/19q co-deletion also predicted better response to chemotherapy (p = 0.007). Grade 3/4 toxicities were mainly hematological. Significantly improved HRQL in the future uncertainty domain of the brain cancer module was seen after cycle 4 (p < 0.001). This trial achieved outcomes similar to those reported previously. Toxicities from dose-intense temozolomide were manageable. Improvement in at least one HRQL domain increased over time. This trial supports the further study of first-line temozolomide monotherapy as an alternative to radiation therapy for patients with newly diagnosed AO/MAO with 1p 19q co-deleted tumors.
authors.affiliation: Brain Tumor & Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue (S70), Cleveland, OH, 44195, USA.
authors.forename: Manmeet S
authors.initials: MS
authors.lastname: Ahluwalia
authors.forename: Hao
authors.initials: H
authors.lastname: Xie
authors.forename: Saurabh
authors.initials: S
authors.lastname: Dahiya
authors.forename: Nooshin
authors.initials: N
authors.lastname: Hashemi-Sadraei
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Paul G
authors.initials: PG
authors.lastname: Fisher
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
authors.forename: Susan
authors.initials: S
authors.lastname: Pannullo
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Newton
authors.forename: Cathy
authors.initials: C
authors.lastname: Brewer
authors.forename: Laura
authors.initials: L
authors.lastname: Wood
authors.forename: Richard
authors.initials: R
authors.lastname: Prayson
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: David M
authors.initials: DM
authors.lastname: Peereboom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D063868:Patient Outcome Assessment; D011379:Prognosis; D011788:Quality of Life; D015996:Survival Rate; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide