According to the ECOG 3598 study published early online in the Journal of Clinical Oncology, the addition of thalidomide to chemoradiotherapy increased toxicities but does not improve survival in patients with locally advanced non–small-cell lung cancer (NSCLC).

The trial involved a total of 546 patients with unresectable stage III NSCLC. All patients received induction chemotherapy with paclitaxel (225 mg/m2) and IV carboplatin (area under the curve 6) on day one, every three weeks for two cycles. A total of 271 patients on the investigational arm also received a starting dose of 200 mg thalidomide daily that was increased by 100 mg every week as tolerated up to a total daily dose of 1,000 mg. After induction therapy, patients with a response or stable disease underwent thoracic radiation therapy beginning between day 43 and 50 from the start of induction therapy. The primary objective of this study was to compare the survival of patients with unresectable stage III non–small-cell lung cancer (NSCLC) treated with combined chemoradiotherapy with or without thalidomide.

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 (PC) arm, compared with 16.0 months (P = 0.99), 7.8 months (P = 0.96), and 38.2% (P = 0.47), respectively, for patients in the paclitaxel/carboplatin/thalidomide (TPC) arm.

The following data were reported for adverse effects:

• Overall, grade 3 adverse events were seen more often in the TPC than the PC arm (53% v 44%; P=0.004)

• There was no difference in grade 4 and 5 incidence between the two regimens, with 32% of grade 4 and 1% of grade 5 events observed in each arm

• There was a statistically significantly higher rate of grade 3 or greater thomboembolic events in the TPC arm (11%) compared with the control arm (3%; P<0.001), even with the addition of prophylactic aspirin.

• Patients in the TPC arm had a statistically significantly higher incidence of the following grade 3 toxicities compared with patients in the PC arm: fatigue, depressed consciousness, dizziness, sensory neuropathy, tremor, constipation, dyspnea, hypoxia, hypokalemia, rash, and oedema.

The researchers concluded that thalidomide does not offer an additional therapeutic strategy in the management of NSCLC as it did not improve progression-free survival, overall survival or overall response.