Challenges in advanced NSCLC: optimizing platinum-based chemotherapy and treating special populations.

Platinum-based chemotherapy is the standard of care for patients with advanced non-small cell lung cancer, but clinical challenges remain in determining safe and effective treatments for elderly patients and those with performance status 2, who may not be able to tolerate standard regimens. Because carboplatin is associated with a better tolerability profile than cisplatin, with comparable efficacy, carboplatin-based combination regimens are the "community standard of care". The standard of care appropriate for elderly and performance status 2 patients, however, remains controversial. Under-representation of elderly and performance status 2 patients in clinical trials and fears about the suitability of treating such patients with the same therapies as those used in younger and healthier patients, hinders evidence-based decisions regarding care. Recent evidence indicates that "fit" elderly patients respond to platinum-based doublet therapy with reasonable tolerability. Particularly in the presence of substantial comorbidities, patients with poor performance status are less responsive to chemotherapy than healthier patients. However, the decision to proceed with treatment may be appropriate for selected patients. In clinical trials with performance status 2 patients, greater clinical efficacy was seen with carboplatin-based doublets than single-agent paclitaxel, suggesting that carboplatin-based doublets can be effective treatment in this population. Optimal carboplatin administration in combination with paclitaxel is yet to be determined, but phase II trials indicate that weekly paclitaxel plus monthly full-dose carboplatin may offer enhanced tolerability and efficacy versus standard every-3-week schedules. A phase III trial comparing these schedules has been completed and will be reported in 2004.