(Chemotherapy Advisor) – Patients with unresectable stage III non–small cell cancer (NSCLC) treated with chemotherapy and thalidomide had no clinical benefit from the thalidomide and a higher incidence of toxicities, including thromboembolic events, the Eastern Cooperative Oncology Group (ECOG) 3598 study concluded in a study published ahead of print in the January 23, 2012 issue of Journal of Clinical Oncology.

A total of 546 patients were randomly assigned to receive two cycles of induction paclitaxel 225mg/m2 and carboplatin AUC 6 followed by 60Gy thoracic radiation concurrently with weekly paclitaxel 45mg/m2 and carboplatin AUC 2 (n=275) or the same regimen with thalidomide 200 mg daily (n=271). Thalidomide doses could be increased to 1,000mg/day based on patient tolerability.

Median follow-up for living patients (n=53) was 61.8 months. Overall, there was no significant difference in OS, the primary end point, between the two groups: median OS was 16 months in the thalidomide arm vs. 15.3 months in the control arm (HR=1.00; P=.99), noted Tien Hoang, MD, Wisconsin Institute for Medical Research, Madison, WI, on behalf of ECOG 3598 colleagues. The trial was recommended to be stopped for futility at the third interim analysis of OS.

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Progression-free survival was 7.8 months in the thalidomide arm vs. 7.4 months in the control arm (P=.96) and overall response rate was 38.2% vs. 35%, respectively (P=.47).

An increase in thromboembolic events (grade 3 or higher) was associated with thalidomide (11% vs 3%; P<.001); taking a low-dose aspirin daily did not appear to prevent or reduce these events, the investigators noted. Other grade 3 or higher toxicities associated with thalidomide included sedation, fatigue, hypotension, constipation, edema, tremor, and sensory neuropathy.

An accompanying editorial by Roy Decker and Thomas Lynch, MD suggests that “it is possible that thalidomide is a far less potent inhibitor of tumor angiogenesis than previously assumed.” Nonetheless, “there are some hints from this study that additional chemotherapy can improve outcome.”

Abstract, Journal of Clinical Oncology, January 23, 2012