Thalidomide increased thrombotic events, showed no survival benefit in SCLC

Thalidomide in combination with chemotherapy showed no improvement in survival and was associated with an increase in thrombotic events in patients with small cell lung cancer, according to the results of a phase-3 trial.

Researchers randomly assigned 724 patients on chemotherapy (etoposide and carboplatin every three weeks for up to six cycles) to thalidomide or placebo 100 mg to 200 mg daily for two years.

Median OS was similar in the thalidomide group (10.1 months) and placebo group (10.5 months). No difference was observed after adjustment for variables (HR=1.11; 95% CI, 0.94-1.32).

In subgroup analysis, survival was similar in patients with limited disease (HR for death=0.91; 95% CI, 0.73-1.15) but was worse in patients with extensive disease assigned thalidomide (HR=1.36; 95% CI, 1.10-1.68).

No differences were observed between the two groups for local relapse rate, distant relapse rate or PFS.

Thrombotic events, specifically pulmonary emboli and deep vein thrombosis, were two times more likely to occur in the thalidomide group (19%) than in the placebo group (10%; 95% CI, 1.41-3.20).

Thalidomide may not be an effective anti-angiogenic drug as initially assumed or small cell lung cancer may be the wrong cancer to test thalidomide, according to the authors of an accompanying editorial.

“Rather than running from failure to failure, it may be more reasonable to go back to experimental work, including the development and analysis of transgenic small cell lung cancer models, to better understand [its] biology and identify robust therapeutic targets,” they said.

Lee SM. J Natl Cancer Inst. 2009;101:1049-1057.