The addition of thalidomide to chemoradiotherapy provides no survival benefit and increases toxicity in patients with unresectable stage III non-small cell lung cancer.
Tien Hoang, MD
The addition of thalidomide to chemoradiotherapy provides no survival benefit and, in fact, increases toxicity in patients with unresectable stage III non—small cell lung cancer (NSCLC), according to data from a phase III Eastern Cooperative Oncology Group (ECOG) study.
“Therefore, we do not recommend the use of thalidomide in this setting,” said Tien Hoang, MD, assistant professor in the Department of Medicine at the Wisconsin Institute for Medical Research in Madison, and coauthors.
The investigators randomized patients to 2 cycles of induction paclitaxel 225 mg/m2 and carboplatin area under the curve (AUC) 6, followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel 45 mg/m2 and carboplatin AUC 2, or to the same treatment in combination with the anti-angiogenic agent thalidomide at a starting dose of 200 mg daily. The protocol permitted an increase in thalidomide dose up to 1000 mg daily based on patient tolerability.
While combined chemoradiotherapy is the standard of care for patients with locally advanced NSCLC with high-performance status and minimal weight loss, the treatment is usually not curative because of the high risk of local and distant failure, the researchers said. Thus, new treatment approaches are desperately needed.
Thalidomide is an oral agent that was originally used as a sedative and antiemetic but was later pulled from the market after causing birth defects. Later on, experimental research demonstrated the anti-angiogenic activity of thalidomide, and the drug has since been approved for the treatment of multiple myeloma.
Because of thalidomide’s relative lack of myelosuppression and the ease with which it can be combined with chemotherapy for the treatment of myeloma and other tumors, the authors felt it might prove useful in the setting of chemoradiotherapy for stage III NSCLC.
At the time of the efficacy analysis, 493 of 546 eligible patients had died. The median follow-up for living patients was 61.8 months. The primary endpoint of the study was overall survival.
The data showed that the median overall survival, progression-free survival, and overall response rate were 15.3 months, 7.4 months, and 35.0%, respectively, for control patients versus 16.0 months (P = .99), 7.8 months (P = .96), and 38.2% (P = .47), respectively, for patients who received thalidomide.
In addition, thalidomide use was associated with a higher incidence of grade 3 or greater toxicities including sedation, fatigue, hypotension, constipation, edema, tremor, sensory neuropathy, and thromboembolism.
The authors noted that while low-dose aspirin did not prevent or decrease the incidence of thromboembolic events (11% of thalidomide and 3% of control patients; P < .001), there was no thromboembolism-associated mortality in patients taking aspirin prophylactically. However, they emphasized that they do not have enough data in order to be able to comment definitively on the efficacy of aspirin in lowering mortality related to thromboembolic events.
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 [published online ahead of print January 23, 2012]. J Clin Oncol. 2012;30:616-622.