Influence of Altering Administration Sequence of Docetaxel, Gemcitabine and Cisplatin in Patients with Advanced Non-small Cell Lung Cancer

Background: A phase II study of a triplet chemotherapy with the administration sequence of gemcitabine (GEM), docetaxel (DCT) and cisplatin (CDDP) (OLCSG9908) was previously conducted in patients with advanced non-small cell lung cancer (NSCLC). The objective response rate was 34% and the median survival time (MST) and 1-year survival rate were 11.7 months and 49%, respectively. In an in vitro study of different sequence exposures to GEM and DCT, it was reported that the synergistic effect was more prominent using the administration sequence of DCT followed by GEM compared with the reverse sequence. In order to estimate the effects of the administration sequence, a phase II study of the same triplet chemotherapy was conducted with the administration sequence of DCT, CDDP and GEM. Patients and Methods: Patients with unresectable stage IIIB/IV NSCLC were eligible. All drugs were given intravenously on days 1 and 8, and repeated every 4 weeks for up to 4 cycles. DCT (30 mg/m 2 ) was given first, followed by CDDP (40 mg/m 2 ) and GEM (800 mg/m 2 ). Results: Thirty-four patients were enrolled on this study (OLCSG0101). The objective response rate was 38% (95% CI: 22-56%). As grade 3/4 hematological toxicities, neutropenia, thrombocytopenia and anemia were observed in 70%, 41% and 21%, respectively, and febrile neutropenia was observed in 12%. As grade 3/4 non-hematological toxicities, vomiting and liver dysfunction were observed in 15% and 18%, respectively. These toxicities were manageable by conventional therapy. The MST and 1-year survival rate were 13.3 months (95% CI: 7.8-18.7 months) and 55% (95% CI: 38-73%), respectively. These results were similar to those of OLCSG9908. Conclusion: This triplet chemotherapy is well tolerated and effective in patients with advanced NSCLC, however, the treatment outcome was not significantly influenced by the administration sequence of DCT and GEM.