Treatment of small cell lung cancer: the state of the art.

Many innovations have been tested to improve the power of chemotherapy for SCLC including: drug diversity enhancement, dose and dose-intensity escalation, incorporation of new agents, and resistance modification. Although superiority of combination chemotherapy over monotherapy has been shown, clinical trials have failed to demonstrate a clearly superior multiagent regimen. When dose and dose-intensity are diminished from standard levels, the effect is detrimental for both limited and extensive stage SCLC. Trials of dose and dose-intensity above standard levels have not yet shown advantages for patients with extensive stage SCLC. However, the only two randomized trials of chemotherapy dose escalation for limited SCLC show statistically significant survival benefits. The optimal intensity of chemotherapy for limited SCLC has not been defined. State-of-the-art chemotherapy for extensive SCLC could be CAV, EP, or CAV/EP but EP has generally been favored because it is associated with less myelotoxicity and four cycles are considered adequate rather than 6 cycles of the others. EP is widely regarded as state-of-the-art chemotherapy for limited SCLC particularly because this regimen can be integrated with concurrent thoracic irradiation with acceptable toxicity. Early thoracic irradiation with concurrent EP chemotherapy is state-of-the-art treatment for limited SCLC, however, it must be conceded that EP has never been shown to be superior to any other chemotherapy regimen in a phase III trial of either limited or extensive SCLC. Current state-of-the-art treatment for limited SCLC can result in actual 5-year survival rates of at least 20%; declaration of a statistically significant improvement will require sample sizes than most clinical trials performed to date.