7201 Background: The role of non-platin combinations has not yet been fully demonstrated. CPT-11 and docetaxel (Taxotere) have additive activity in vitro and in vivo. The optimal timing of administration of both drugs is not yet well defined. UGT1A1 has been shown to be the isoform responsible for SN38 (the major active metabolite of CPT-11) glucuronidation. XPD and XRCC1, are essential components in DNA repair system. The present study assessed whether these SNPs could influence the response, toxicity and survival in irinotecan-taxotere-treated advanced NSCLC P. Methods: Treatment consisted in CPT-11: 80 mg/m2 followed by Docetaxel 40mg/m2 d 1 and 8, administered every 3 weeks. TaqMan 5’ nuclease assay was used to examine SNPs in genomic DNA obtained from peripheral blood lymphocytes. 69 P were enrolled, 58 male and 11female. Median age was 66 years (range 39 - 79); 31 P had adenocarcinoma, 24 squamous cell carcinoma and 14 undifferentiated large cell carcinoma. 10 had stage IIIB and 59 stage IV. 248 courses have been administered (median 3, range 1- 8). To date all P were evaluable for toxicity and SNPs assessment and 59 for efficacy. Results: 13 (22%) P achieved a partial remission, without complete remissions. 18 (30.5%) showed stable disease and 28 (47.5%) progression. With a median of follow-up of 3,7 months the median time to progression (mTTP) was 4.8 months (95% C.I: 2.6–6.9) and median survival (MS) 6.9 months (95% C.I: 4 -9.8). Grade 3–4 toxicity was as follows: diarrhea 43%, neutropenia 15%, nausea and vomiting 16%, asthenia 12% of the P. Other toxicities were less common, and grade 1–2. Dose reduction was required in 23% of P with 10% of cycles delayed. However, the median of relative dose intensity was 0.95 for both drugs. No differences in toxicity, reponse rate, mTTP and MS were observed according to SNPs analyzed. Conclusions: CPT-11 - Docetaxel is active in untreated advanced NSCLC. The profile of toxicity was acceptable. This combination seems to be a good alternative to a platin-based chemotherapy. To date no differences in outcome were observed according to SNPs assesed. No significant financial relationships to disclose.