Phase II trial of second-line erlotinib and digoxin in patients with non-small cell lung cancer (NSCLC)

Abstract

e19077 Background: There is laboratory evidence that digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant, but not benign cells to induction of apoptosis. Epidemiologic studies also have shown beneficial effects of digitalis in breast cancer incidence. At ASCO 2007 our group presented a phase II study showing encouraging results by adding digoxin to bio-chemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for NSCLC with a response rate (RR) of 10%. This study hypothesized, that adding digoxin to erlotinib may improve the RR and time to progression (TTP) in NSCLC. Methods: This was a phase II trial using daily 150 mg erlotinib and digoxin 0.25 mg. The digoxin dose was adjusted to keep levels between 1–2 ng/ml. Patients with progressive disease (PD) after chemotherapy were enrolled, if they had an ECOG 0–2 and good organ function. CT scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred. Results: Patient accrual lasted from 3/06–8/08 and was stopped early at time of interim analysis. Twenty eight patients were enrolled and 24, who completed at least 6 weeks of therapy, are presented here. All patients had unresectable stage III/IV at diagnosis. Median age was 61 (34–78), 14 were female, 17 had prior radiation (not involving the target lesions), 23 had one prior chemotherapy and 1 subject had two. Only one patient was a never smoker. Histologies were 50% adenocarcinoma, 30% squamous and 20% unspecified. One patient had a PR, 9 SD, and 14 PD. The median TTP was 61 days (9–366) and median survival 157 days (9–844). Side effects were similar to erlotinib single agent with no treatment related mortality. There were no unexpected or increased adverse events related to digoxin. Conclusions: Digoxin did not increase the response rate of erlotinib in the treatment of progressive NSCLC. TTP and survival seen in this study were similar to the published results with erlotinib alone. This combination does not warrant further clinical studies in NSCLC. No significant financial relationships to disclose.