Sequencing of single-agent (SA) docetaxel (T) and gemcitabine (G) therapy for patients (pts) with advanced non-small cell lung cancer (NSCLC): Results of three consecutive randomized trials.

7035 Background: Standard doublet chemotherapy (DCT) is often clinically inappropriate. Since T and G show efficacy and favourable toxicity as SAs in 1st- and 2nd-line setting, sequencing of T and G may be an equally effective alternative to DCT for palliation. Three studies (S1-S3) were conducted: two to identify an optimal SA-sequence (S1/S2), and one to compare sequential SA to a platin-free doublet (S3).,Common eligibility criteria included histologically confirmed stage IIIB or IV, performance status (PS) 0-2, and no prior chemotherapy. S1/S2 examined treatment feasibility (TF) of G or T with introduction of the opposite agent in case of progression. TF was defined as pt ability to receive ≥2 cycles (cyc) of 1st-line and if progressive ≥2 cyc of 2nd-line therapy and to survive ≥7 months (mos). In S1, G 1000 mg/m and T 35 mg/m was given on days (d) 1, 8, 15 (q4w) and in S2, G 1250 mg/m (d 1, 8) and T 100 mg/m (d 1; q3w). In S3, pts received G 1000 mg/m (d 1, 8) and T 75 mg/m (d 1; q3w) either concomitantly (G+T; 6 cyc) or sequentially (G→T; 3 cyc each). Primary endpoint of S3 was clinically relevant haematotoxicity (CRHT) defined as thrombocytopenia with platelet transfusions, anaemia with RBC-transfusions or febrile neutropenia with i.v. antibiotics (IVAB).,819 pts were included (1998-2004): 85% of pts had stage IV disease and PS≤1. In S1 and S2 for (G→T)/(T→G) respectively: TF was 28/20% and 38/49% (p=.04); median survival (MS) was 9.0/5.0 mos (p=.03) and 6.3/8.6 mos; and median time to progression (TTP) was 4.3/2.2 mos and 2.4/3.3 mos. In S3, CRHT occurred less frequently with SA therapy (p<.001), transfusions and IVAB treatment days were less common. QoL also favoured SA therapy. For (G+T)/(G→T), MS was 7.3/7.4 mos, response rate was 33/22% (p=.05) and TTP was 6.3/4.9 mos (p=.04).,Sequencing modern SA was effective and well tolerated. Weekly T and G regimens seem less feasible than 3-weekly but compared to the nonplatinum doublet CRHT and IVAB are reduced with better QoL and cost-effectiveness. [Table: see text].