Adding Thalidomide to Chemoradiation Increases Toxicities but Not Survival for Stage III Non–Small Cell Lung Cancer


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Adding thalidomide (Thalomid) to the third-generation chemotherapy doublet of paclitaxel and carboplatin and radiation for patients with stage III non–small cell lung cancer (NSCLC) increased toxicities but did not improve survival. These results from the Eastern Cooperative Oncology Group (ECOG) 3598 study were reported in the Journal of Clinical Oncology.1

A total of 546 patients were randomly assigned to the control arm, receiving two cycles of induction paclitaxel at 225 mg/m2 and carboplatin at area under the curve (AUC) 6 followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel at 45 mg/m2 and carboplatin at AUC 2, or to the experimental arm, receiving the same treatment in combination with thalidomide at a starting dose of 200 mg daily. The protocol allowed an increase in thalidomide dose by 100 mg every week as tolerated, up to 1,000 mg daily.

“Median overall survival, progression-free survival, and overall response rate were 15.3 months, 7.4 months, and 35.0%, respectively, for patients in the [paclitaxel/carboplatin] arm, in comparison with 16.0 months (P =  .99), 7.8 months (P =  .96), and 38.2% (P = .47), respectively, for patients in the [thalidomide/paclitaxel/carboplatin] arm,” the authors reported. “Retrospective, unplanned analysis also failed to identify subgroups of patients who may derive benefits from this investigational regimen. Furthermore, the use of thalidomide was associated with higher incidence of grade 3 or greater toxicities, such as sedation, fatigue, hypotension, constipation, edema, tremor, sensory neuropathy, and thromboembolism.”

Failure of Thalidomide

The authors noted that three European trials, two for NSCLC and one for small-cell lung cancer, also “failed to show a survival advantage with the addition of thalidomide to chemotherapy.”

An editorial2 accompanying the article noted: “The failure of thalidomide to recapitulate the improvement seen with bevacizumab [Avastin] and combination chemotherapy in patients with advanced disease, or to improve overall survival with chemoradiotherapy in the study by Hoang et al in patients with stage III disease, suggests that there is little or no role for thalidomide as an antiangiogenic agent in NSCLC.” ■

References

1. Hoang T, Dahlberg SE, Schiller JH, et al:  Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: The ECOG 3598 study. J Clin Oncol. January 23, 2012 (early release online).

2. Decker RH, Lynch TJ: Unmet challenges in the use of novel agents in locally advanced non-small-cell lung cancer. J Clin Oncol. January 23, 2012 (early release online).



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