Chemotherapy for non-small cell lung cancer: have we reached a new plateau?

The last decade has seen the introduction of several new chemotherapeutic agents that have activity against non-small cell lung cancer (NSCLC) and produce single-agent response rates of > or = 20% in previously untreated patients with advanced tumors. Furthermore, the results of phase I-II trials have shown that the agents can be combined safely with cisplatin or carboplatin and that most combinations result in response rates of 35% to 40% or more. Gemcitabine, paclitaxel, vinorelbine, and tirapazamine have all been studied in combination with cisplatin in trials that compared the combinations with cisplatin alone. All trials reported response rates that were significantly higher for the combination arm and, with the exception of the paclitaxel trial, median and 1-year survival rates were also significantly greater. Vinorelbine as a single agent was compared with vinorelbine in combination with cisplatin in three studies. Although response and survival rates were longer for the combination arms, single-agent vinorelbine produced median survivals of longer than 30 weeks in all trials and a 1-year survival rate of 30% in one study. Single-agent gemcitabine was compared with the combination of etoposide and cisplatin in two trials. In each study, the response to gemcitabine was equal to that of the combination arm, and the 1-year survival rate was actually superior for the single-agent gemcitabine arm. Combinations of the new agents with cisplatin or carboplatin also have been evaluated in randomized phase III trials and compared with standard chemotherapy regimens for the treatment of NSCLC. The vinorelbine/cisplatin combination was found to be superior to vindesine/cisplatin. Paclitaxel/cisplatin and gemcitabine/cisplatin were both found to be superior to etoposide/cisplatin. Survival gains have been modest, with median survival ranging from approximately 8 to 10 months and 1-year survival rates with the new regimens ranging from 32% to 41%. The new chemotherapy regimens have resulted in modest benefit and have set a new standard for the treatment of advanced NSCLC.