title: The role of temozolomide in the management of patients with newly diagnosed anaplastic astrocytoma: a comparison of survival in the era prior to and following the availability of temozolomide.
abstract: Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan-Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p < 0.001). Median OS was 32 months (95 % CI 23-43). Survival was longer in the post-2004 cohort (37 mo, 24-64) than pre-2004 (27 mo, 19-40; HR 0.75, 0.53-1.06, p = 0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36 % reduced risk of death (HR 0.64, 0.44-0.91, p = 0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of newly-diagnosed AA.
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, Cancer Research Building II, 1550 Orleans St, Baltimore, MD, 21287, USA. rstrowd@wakehealth.edu.
authors.forename: Roy E
authors.identifier: http://orcid.org/0000-0001-6651-5267
authors.initials: RE
authors.lastname: Strowd
authors.affiliation: Department of Internal Medicine, Saint Agnes Hospital, Baltimore, MD, 21287, USA.
authors.forename: Inas
authors.initials: I
authors.lastname: Abuali
authors.affiliation: Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Grossman
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D002330:Carmustine / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011344:Procarbazine / Q000008:administration & dosage; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine; D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide
keywords: Anaplastic astrocytoma; Chemotherapy; Glioma; Temozolomide