Phase II study of Cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097)

Inhibition of angiogenesis is a novel strategy for the treatment of cancer. We evaluated the safety and efficacy of cediranib, a potent small molecule inhibitor of the vascular endothelial growth factor receptor, in patients with refractory or recurrent small cell lung cancer (SCLC).

Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a majority of SCLC patients.

Patients with SCLC with progression after prior platinum-based chemotherapy only; performance status (PS) of 0 to 2; and adequate bone marrow, renal, and hepatic function were included. The dose of cediranib was 45 mg PO once a day for the first 12 patients and was reduced to 30 mg PO once a day for the subsequent patients because of intolerance of the higher dose. Treatment was given on a daily continuous schedule. The primary end point was determination of the response rate.

Twenty-five patients were enrolled. Patient characteristics were as follows: 13 men; median age 61 years; PS 0 (12 pts), PS 1 (12 pts). A median of two cycles were administered. Salient grade 3/4 toxicities were fatigue, diarrhea, hypertension, proteinuria, and elevated liver enzymes. Tolerability was better with the 30 mg dose once a day. Nine patients had stable disease, but none had a confirmed partial response. The median progression-free survival and overall survival were 2 and 6 months, respectively. Response criteria to proceed to full accrual were not met. Increase in circulating endothelial cell count was noted at the time of progression in several patients. Conclusions: Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a majority of SCLC patients.