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Published on: May 15, 2019
Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized,
Siow Ming Lee1, Penella J Woll, Robin Rudd
1Department of Oncology, University College Hospital, 250 Euston Road, London, UK. sm.lee@uclh.nhs.uk
Background:
Cancer cells rely on angiogenesis for growth and dissemination, and small cell lung cancer (SCLC) is a highly angiogenic tumor. We evaluated thalidomide, an anti-angiogenic agent, when combined with chemotherapy and as maintenance treatment.
Methods:
A total of 724 patients (51% with limited and 49% with extensive disease) were randomly assigned to receive placebo or thalidomide capsules, 100-200 mg daily for up to 2 years. All patients received etoposide and carboplatin every 3 weeks for up to six cycles. Endpoints were overall survival, progression-free survival, tumor response rate, toxicity, and quality of life (QoL). Hazard ratios (HRs) for comparing thalidomide against placebo were estimated using Cox regression modeling. Statistical tests were two-sided.
Results:
The median overall survival was 10.5 months (placebo) and 10.1 months (thalidomide) (HR for death = 1.09, 95% confidence interval [CI] = 0.93 to 1.27; P = .28). Among patients with limited-stage disease, there was no evidence of a survival difference (HR for death = 0.91, 95% CI = 0.73 to 1.15), but among patients with extensive disease, survival was worse in the thalidomide group (HR for death = 1.36, 95% CI = 1.10 to 1.68). Progression-free survival rates were also similar in the two groups (HR = 1.07, 95% CI = 0.92 to 1.24). Thalidomide was associated with an increased risk of having a thrombotic event, mainly pulmonary embolus and deep vein thrombosis (19% thalidomide vs 10% placebo; HR = 2.13, 95% CI = 1.41 to 3.20; P < .001). There were no statistically significant differences between treatments in hematological and nonhematological toxic effects, except more patients in the thalidomide group had rash, constipation, or neuropathy. Overall, QoL scores were similar in the two treatment groups, but thalidomide was associated with less insomnia and diarrhea and more constipation and peripheral neuropathy.
Conclusions:
In this large randomized trial, thalidomide in combination with chemotherapy did not improve survival of patients with SCLC but was associated with an increased risk of thrombotic events.
