Extended adjuvant temozolomide for treatment of newly diagnosed glioblastoma multiforme

Abstract

The standard of care for newly diagnosed glioblastoma multiforme (GBM) is temozolomide (TMZ) chemotherapy given concurrently with radiation for 6 weeks followed by 6 months of adjuvant TMZ. Originally, patients in Alberta were treated with only six cycles of adjuvant TMZ regardless of clinical status but institutional policy was amended to allow up to 12 cycles of adjuvant therapy for patients experiencing at least stable disease and minimal toxicity. We conducted a population-based analysis to determine if extended adjuvant TMZ treatment (i.e., more than six cycles) confers a survival advantage as compared to the standard six cycles for newly diagnosed GBM patients. Patient data was collected from the Alberta Cancer Registry and patient charts. Progression free--and overall survival was determined in patients receiving six cycles of adjuvant TMZ and compared with that of patients receiving more than six cycles. Patients in whom adjuvant chemotherapy was stopped at cycle six experienced a median survival of 16.5 months, whereas, those who received more than six cycles survived for 24.6 months (p = 0.031). Extended adjuvant therapy was not associated with increased toxicity. In multivariate analysis, adjuvant monthly Temozolomide for more than six cycles was an independent prognostic factor for both progression free--and overall survival. These data suggest extended adjuvant temozolomide (i.e., more than six cycles) should be considered in patients with newly diagnosed GBM.

Targeting the TGFβ signalling pathway in disease

“…74 were premature. Because of other advances in both neurosurgical procedures and first-line standard of care for patients with glioblastoma 212 , the SAPPHIRE Phase III trial of trabedersen was recently halted owing to patient recruitment issues (ClinicalTrials.gov identifier: NCT00761280). Nevertheless, the drug has undergone a Phase I/II trial for patients with advanced pancreatic cancer, MetM or metastatic colorectal carcinoma, and showed excellent safety and encouraging survival results (ClinicalTrials.gov identifier: NCT00844064) 84 .…”

The roles of TGFβ in the tumour microenvironment

“…Several Phase I and Phase II clinical trials of TGFβ-neutralizing antibodies and of small-molecule inhibitors to both ligand and receptor have so far been shown to be safe and efficacious; many trials are still accruing patients 121–124 . For a complete and comprehensive examination of therapeutic treatments targeting the TGFβ pathway in malignant and non-malignant disease progression, see REF.…”

Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma

“…4 A few smaller, single-institution, retrospective studies claimed prolonged survival of patients with glioblastoma who received extended TMZ treatment beyond 6 cycles. [5][6][7][8] The major limitation of all these studies, beyond the retrospective nature, is the comparison of patients who were treated with at least 7 cycles of TMZ to patients who received #6 cycles and therefore to patients who in most cases stopped TMZ because of tumor progression. Long-term administration of TMZ was associated with an acceptable safety profile in patients diagnosed with World Health Organization grade III and IV gliomas who received long-term TMZ treatment for at least 12 cycles.…”