Researchers from the U.K. have reported that treatment with a combination of thalidomide (Thalomid®) and chemotherapy did not improve survival among patients with small cell lung cancer, and resulted in a higher risk of blood clots than treatment with chemotherapy alone. The results of this study were published in the August issue of the Journal of the National Cancer Institute.[1]

Small cell lung cancer (SCLC) accounts for approximately 15-20% of all lung cancers. Treatment of SCLC usually involves chemotherapy, but many cancers recur or progress following treatment.

Thalidomide is a drug that inhibits the development of new blood vessels. This may slow or stop cancer growth by depriving the cancer of oxygen and nutrients. Thalidomide is approved for the treatment of multiple myeloma.

A previous study from France reported that the addition of thalidomide to chemotherapy improves survival in patients with extensive SCLC. This trial included 119 patients with extensive SCLC, all of whom initially underwent chemotherapy with a regimen referred to as PCDE (cisplatin, cyclophosphamide, etoposide, and doxorubicin). Patients received prophylactic Neupogen® (filgrastim) with each course of chemotherapy. If patients achieved an anticancer response to PCDE, they were then treated with additional PCDE plus placebo or thalidomide and PCDE. At one year 49% of patients treated with thalidomide were alive compared with only 30% of patients treated PCDE only. Nearly half of the patients treated with thalidomide were still alive at one year compared with approximately nine months for those treated with PCDE only.

To evaluate thalidomide in combination with chemotherapy for the treatment of SCLC, researchers in the U.K. conducted a Phase III clinical trial among 724 patients. Roughly half had limited-stage SCLC, and half had extensive SCLC.

All patients received chemotherapy with etoposide and carboplatin every three weeks for up to six cycles. In addition, patients were assigned to receive either thalidomide capsules or a placebo daily for up to two years.

• Overall survival was 10.5 months among patients in the placebo group and 10.1 months among patients in the thalidomide group. Survival without cancer progression was also similar in the two study groups.
• In analyses by disease stage, thalidomide was found to worsen overall survival among patients with extensive SCLC. Among patients with limited-stage SCLC, thalidomide did not significantly affect overall survival.
• Rates of blood clots (mainly pulmonary embolus and deep vein thrombosis) were higher among patients in the thalidomide group than among patients in the placebo group. Blood clots occurred in 19% of patients in the thalidomide group compared with 10% of patients in the placebo group.

Comments: These results suggest that the addition of thalidomide to chemotherapy does not benefit—and may harm—patients with small cell lung cancer who are treated with etoposide and carboplatin. However, the French study suggests that thalidomide is of benefit if administered after four-drug induction chemotherapy. Thus, it cannot be definitively concluded that thalidomide has no role in the treatment of SCLC.

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