Interferon alpha + 13-cis-retinoic acid modulation of BCL-2 + paclitaxel for recurrent SCLC.

19048 Background: While SCLC is highly responsive to initial chemotherapy, second line therapy is more challenging, since most cases develop resistance to chemotherapy after first line therapy. SCLC is known to over-express bcl-2, and such over-expression can produce drug resistance by inhibiting apoptosis. The combination of CRA and IA was shown to reduce bcl-2 expression, and potentially enhance drug sensitivity to several agents such as taxanes.,The primary endpoints were to evaluate objective response rate (ORR) defined per RECIST and toxicities in patients (pts) with SCLC recurrent > 60 days from prior chemotherapy and who were then treated with IA, and CRA modulation of bcl-2 plus P. Secondary endpoints include progression-free survival (PFS) and overall survival (OS). Eligibility criteria included: ECOG PS 0-3, and adequate hematological, hepatic, and renal function. Pts received IA 6 million U/m SQ, on days 1 and 2, CRA 1 mg/kg PO on days 1 and 2 and P 75 mg/m IV on day 2 each week for 6 weeks then 2 weeks of rest. The study employed a two-stage design with 34 pts entered in the first stage (FS). If more than 12 ORRs were observed, then 42 more pts would be entered. If more than 31 ORRs were observed in 76 pts, then the treatment would be regarded as efficacious.,From 2/04 - 2/07, 37 pts were registered to the FS of this study. Two were ineligible. All pts had measurable disease, 5 pts (14%) had pleural effusion. At the end of the FS 3 ORRs (10.3%, 90% CI = 2.9%, 24.6%), all PRs, had been observed in 29 pts with sufficient data to evaluate ORR. Median follow-up is 14.7mos; median OS is 6.4 mos (3.9-9.7 mos); median PFS is 2.3 mos (1.8-4.6 mos). 21 pts (62%) experienced worst degree toxicity of grade 3 or higher; the most common of which were leukocytes (32%) and neutrophils (26%).,This study was terminated for not meeting the criteria to reopen the second stage of the study. The response and survival data seen were no better than P alone. IA plus CRA plus P did not provide a sufficient clinical benefit for pts with recurrent SCLC to warrant further study of this combination, however analysis of peripheral blood monocytes' bcl-2 protein is ongoing. [Table: see text].