SO124: A Randomized Phase III Trial Comparing Irinotecan/Cisplatin (IP) with Etoposide/Cisplatin (EP) in Patients (pts) with Previously Untreated Extensive Stage Small Cell Lung Cancer (E-SCLC)
The combination of etoposide and cisplatin (EP) is the most widely used chemotherapy regimen for small cell lung cancer. Two large studies looked at using irinotecan and cisplatin (IP), but had conflicting results. The first trial was conducted in Japan and found a significant improvement in overall survival with IP. The follow-up study was conducted in North America and Australia and failed to show a benefit to the newer regimen. It is not clear if the different outcomes were due to ethnic differences in the metabolism of irinotecan. The current study looked at the comparison of EP to IP again to try to determine the best regimen.
645 patients with extensive stage small cell lung cancer participated in the study. The EP arm experienced more neutropenia and thrombocytopenia, while the IP arm experienced more diarrhea. There were no differences seen in overall survival, progression free survival or response rates between the two groups.
This is now the second clinical trial that has failed to demonstrate a survival benefit with IP therapy versus EP therapy in patients with extensive stage SCLC. The authors point out that genetic variability may be responsible for the discrepancy between the two studies. Another potential confounder is cigarette smoking. There have been some data to suggest that smoking affects the metabolism of irinotecan. Unfortunately, smoking status was not recorded in the present study. However, it is also certainly possible, as the authors point out, that the results from the JP511 study were incorrect because it had been stopped early due to toxicities. Nonetheless, from the combined results of the two American trials, it is clear that EP remains the standard of care for extensive stage SCLC.