Tumor treating fields: a new standard treatment for glioblastoma?

PURPOSE OF REVIEW: Tumor treating fields (TTFields), an external therapeutic device with antimitotic properties, is a Food and Drug Administration approved treatment for recurrent glioblastoma (GBM) that has been reported to be efficacious in newly diagnosed GBM as well. RECENT FINDINGS: Preclinical data show that TTFields is an antimitotic agent that additionally augments response to alkylator-based chemotherapy. In a single study, nearly 15% of recurrent GBM treated with TTFields alone display durable responses. Responses may be delayed, sometimes after an initial progression, and are highly correlated to treatment compliance and to survival. In newly diagnosed GBM, a preplanned interim analysis of the phase III randomized trial (standard of care with or without TTFields) showed a statistically significant effect of TTFields resulting in a net gain of 3 months in both progression-free and overall survival. SUMMARY: TTFields is a novel noninvasive therapeutic option for recurrent GBM. The role of TTFields in newly diagnosed GBM will be adjudicated pending publication of the final results of the randomized EF-14 trial. If these results are compelling, this may result in accelerated approval and potentially a new standard of care for newly diagnosed GBM.

Neoplastic meningitis.

Neoplastic meningitis occurs in approximately 5%-10% of all patients with cancer, and aggressive supportive measures are a critical component of comprehensive care. A literature review of the current diagnostic methods, randomized controlled trials, and available treatments was undertaken; and a comprehensive discussion of best-practice supportive care measures is provided. Although the prognosis for those diagnosed with neoplastic meningitis is poor, treatment and supportive care may allow stabilization of neurologic symptoms and afford protection from further neurologic deterioration, allowing patients to maximize their function and independence and adjust their expectations of treatment from cure to palliation.

Salvage therapy with single agent bendamustine for recurrent glioblastoma.

The treatment of recurrent glioblastoma (GBM) remains challenging notwithstanding the recent approval of bevacizumab for this indication. Bendamustine has a bifunctional mechanism of action including alkylation, penetrates the CNS and does not show cross resistance to other alkylator chemotherapies. In a single institution phase 2 trial, patients with recurrent GBM were treated with bendamustine (100 mg/m(2)/day administered intravenously for two consecutive days every 4 weeks). The primary study endpoint was 6-month progression free survival (PFS-6). An interim analysis for futility was conducted according to a Simon two-stage minimax design. Complete blood counts were obtained bimonthly, clinical evaluations and brain imaging every month for the first cycle and bimonthly thereafter. Treatment responses were based upon MacDonald criteria. Sixteen patients were enrolled (nine men; seven women), with a median age of 53 years (range 36-68) and a median Karnofsky performance status of 90 (range 70-100). Nine patients were treated at first relapse and seven at second relapse (five patients were bevacizumab failures). A total of 25 cycles of bendamustine were administered with a median of 1 (range 1-6). Bendamustine-related toxicity was seen in eight patients; lymphopenia in seven (5 grade 3; 2 Grade 4), thrombocytopenia in two (1 Grade 3; 1 Grade 4), and neutropenia in one (1 Grade 3). Fourteen patients have died due to disease progression, two patients are alive and on alternative therapies. Only one patient was progression-free at 6 months, triggering the stopping rule for futility. Bendamustine was reasonably well tolerated but failed to meet the study criteria for activity in adults with recurrent GBM.