Temozolomida para Oligodendroglioma Anaplásico.

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKI D; ALCARAZ, A.; LOPEZ, A; REY-ARES, L.; BARDACH, A.; CIAPPONI, A; BRITO V

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Oligodendrogliomas represent 5 to 20% of glial brain tumors; its incidence is 0.2 every 100,000 individuals per year. Anaplastic oligodendroglioma (OA) is histologically characterized by hypercellularity, nuclear pleomorphism and tumor necrosis, and it corresponds to Grade III in the World Health Organization Classification of Tumours of the Central Nervous System. Its clinical manifestations vary according to its localization and extension; being mean survival three to five years after diagnosis. Its therapeutical approach involves surgery, if possible, followed by radiotherapy and/or chemotherapy (CTX). Among the antineoplastic drugs, recently temozolomide (TMZ) has appeared as an alternative to classical regimens with procarbazine, lomustine and vincristine (PVC), because of its easy administration and better tolerance. Technology TMZ is an orally administered alkylating agent. The standard dose is 150 mg/m2/day administered in 5-day cycles every 28 days, when concomitantly administered with radiotherapy it is reduced to 75 mg/m2/day. The main international regulatory agencies have not approved TMZ for AO treatment, but they have approved it for glioblastoma multiforme and for anaplastic astrocytoma. Purpose To assess the available evidence on the efficacy, safety and coverage related issues regarding to the use of temozolomide in patients with anaplastic oligodendroglioma. Methods A bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems. Results Studies in adult population were identified mainly assessing the use of TMZ in malignant gliomas including AO. One RCT and 11 case series corresponded to recently diagnosed tumors and other 11 case series to recurrent tumors. In the pediatric population, two small case series were identified which are described in the text. Recently diagnosed AO One RCT evaluated the use of radiotherapy versus post-surgical CTX in anaplastic gliomas. Subjects were randomly assigned to radiotherapy (Arm A: 139 subjects), CTX with PCV (Arm B1: 68 individuals) or TMZ (Arm B2: 67 individuals). Among 274 participants, 91 had AO. Mean progression free survival (PFS) was 30.6 months with radiotherapy and 31.9 months with CTX (p=0.87); no differences were reported between PCV or TMZ treated subjects. No differences were reported between both groups regarding overall survival (OS) at 48 months (radiotherapy: 72.6%; 95%CI 63.8 to 81.4 vs. CTX [B1+B2]: 64.6%; 95%CI 54.6 to 74.7). One of the 11 case series worth mentioning because of its size, evaluated TMZ as initial treatment in AO subjects with or without 1p/19q codeletion; in the total group analysis (n= 48 individuals; 80% pure AO), the OS at two years was 88.8% (95%CI 74.9- 95.2). Recurrent AO In one of the 11 series identified, 120 subjects with recurrent malignant gliomas were included. In those diagnosed with AO (n=24), OS at six months was 75% (95%CI 60- 95). In one of the other series assessing TMZ - 13-cis-retinoic acid, in the AO subgroup (n=13 cases) OS at six months was 85% (95%CI 67-100). The U.S. National Comprehensive Cancer Network clinical practice guidelines consider the use of TMZ alone or in combination with radiotherapy as a potential option for de novo AO treatment, and appropriate as one of the initial therapies for recurrent AO. The European Society for Medical Oncology clinical practice guidelines highlight the apparent lack of differences in clinical efficacy between TMZ and the PCV scheme. Coverage policies Only one U.S. sponsor was identified which covers TMZ for AO treatment. Costs In Argentina one TMZ cycle is AR$ 3,447 to AR$ 10,906, approximately U$S 595 ? 1,884 (U.S. dollars, September/2013). Conclusions There is poor quality evidence assessing TMZ for de novo or recurrent AO treatment. It includes only one RCT and several case series in heterogeneous populations with malignant gliomas, among which AO in different clinical conditions is included. In general, the studies do not clearly allow determining the superiority of TMZ over strategies considered as first line such as radiotherapy or PCV. However, the clinical practice guidelines consider TMZ alone or in combination with radiotherapy as a therapeutic option for de novo AO, and as an appropriate alternative among initial treatments in recurrent AO.