“Investigators are seeking to determine whether the combination of eflornithine (alphadifluoromethylornithine) with lomustine can improve survival for patients with recurrent anaplastic astrocytoma (AA). A rare form of brain tumor, AA occurs more often in adults aged 30 to 50 years and accounts for 17% of primary malignant brain tumors. This tumor type is even more rare when it recurs, according to Victor A. Levin, MD, emeritus professor of neurooncology at The University of Texas MD Anderson Cancer Center in Houston and a clinical professor at the University of California, San Francisco, School of Medicine.”
“Treatment with lomustine (Gleostine) plus bevacizumab (Avastin) provided a slightly improved progression-free survival (PFS), but did not demonstrate an overall survival (OS) advantage over treatment with lomustine alone in patients with progressive glioblastoma, according to results of a randomized phase III trial published in theNew England Journal of Medicine.
“There were a total of 329 OS events (75.3%) in patients who received the combination, which did not meet the endpoint for a statistically significant benefit. The median OS was 9.1 months (95% CI, 8.1-10.1) in the group of patients who received the combination of lomustine and bevacizumab and 8.6 months (95% CI, 7.6-10.4) in the monotherapy group (HR, 0.95; 95% CI, 0.74-1.21). Locally assessed PFS was 4.2 months in the combination group versus 1.5 months in the monotherapy group (HR, 0.49; 95% CI, 0.39-0.61).”
The gist: Researchers conducted a clinical trial with volunteer patients to test two drugs, alone and in combination, for recurrent glioblastoma. The two drugs tested were bevacizumab (aka Avastin) and lomustine (aka CeeNU). The researchers found promising results for patients who took both bevacizumab and lomustine, and recommend that further clinical trials be conducted to continue to study the new combination treatment. The patients who participated in the study all had glioblastoma that was treated with temozolomide chemoradiotherapy, but recurred.
“Bevacizumab (Avastin) is frequently used in patients with recurrent glioblastoma, although it is unclear whether responses observed with such treatment result in improved overall survival. In the phase II Dutch BELOB study reported in The Lancet Oncology, Taal et al found that overall survival results supported phase III evaluation of the combination of bevacizumab and lomustine (CeeNU) but not bevacizumab monotherapy…
“In this open-label trial, 153 adult patients from 14 Dutch hospitals with a first recurrence of glioblastoma after temozolomide chemoradiotherapy were randomly assigned between December 2009 and November 2011 to receive oral lomustine at 110 mg/m2 once every 6 weeks, intravenous bevacizumab at 10 mg/kg once every 2 weeks, or combination treatment at the same doses. The primary endpoint outcome was overall survival at 9 months in the intent-to-treat population.
“A preplanned safety analysis after eight patients had received the combination regimen showed that three had grade 3 and two had grade 4 thrombocytopenia, with these toxicities requiring a reduction in bevacizumab dose intensity. The lomustine dose in the combination group was subsequently reduced to 90 mg/m2. In addition to the eight combination recipients getting the higher lomustine dose, 51 received bevacizumab alone, 47 received lomustine alone, and 47 received bevacizumab plus lomustine at 90 mg/m2.
“The investigators concluded, ‘The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies. However, the results in the bevacizumab alone group do not justify further studies of this treatment.’ ”