Thalidomide fails to boost mesothelioma outcomes
By Liam Davenport, medwireNews Reporter
08 May 2013
Lancet Oncol 2013; Advance online publication

medwireNews: Adding maintenance thalidomide to standard first-line chemotherapy does not improve outcomes among patients with malignant pleural or peritoneal mesothelioma, study findings indicate.

The researchers, led by Wieneke Buikhuisen, from the Netherlands Cancer Institute in Amsterdam, studied 222 patients with proven malignant pleural or peritoneal mesothelioma without progression after at least four cycles of first-line treatment with pemetrexed with or without cisplatin or carboplatin.

The patients were randomly assigned to receive thalidomide 200 mg per day, after a 2-week run-in of 100 mg per day, plus active supportive care or active supportive care alone until disease progression. Thalidomide was continued for at least 1 year or until unacceptable toxicity.

In all, 104 patients in the thalidomide group and 107 in the active supportive care group experienced disease progression over a median follow up of 33.1 months. The median time to progression was comparable at 3.6 months and 3.5 months in the thalidomide and active supportive care groups, respectively.

There were 92 deaths in the thalidomide group and 93 in the active supportive care group, with no significant difference in median overall survival, at 10.6 months and 12.9 months, respectively.

Grade 3 or 4 adverse events were experienced by 39% of thalidomide patients, over a mean treatment duration of 12.3 weeks, and by 28% of those in the active supportive care group.

Two thalidomide patients reported neurosensory events, compared with none in the active supportive care group, while cardiac events were reported by two and three patients, respectively, and thromboembolic events by three and no patients, respectively.

In a biomarker analysis, neither vascular endothelial growth factor, basic fibroblast growth factor, interleukin 6, cytokeratin fragment (CYFRA) 21.1, or soluble mesothelin-related peptide were associated with response to treatment on multivariable analysis. However, interleukin 6 and CYFRA scores were associated with overall survival, at hazard ratios of 1.6 and 1.4, respectively.

The team says that their findings add to evidence that thalidomide is ineffective for treating solid tumors. However, they note in The Lancet Oncology, that the potential prognostic role of interleukin 6 and CYFRA 21.1 in thalidomide-treated mesothelioma may be worth exploring.

Writing in an accompanying editorial, Harvey Pass, from the NYU Langone Medical Center in New York, USA, says that researchers need to "pick up the pace" in the quest for new treatments for the orphan disease.

"The outcome means that despite our greatest efforts to understand the biology of this disease, and to target promising pathways that seem to contribute to mesothelioma progression, we have no idea which of these pathways is most important, and specifically in which patients we should target that pathway," he concludes.

medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

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