Etoposide (VP-16) and cisplatin in previously treated small-cell lung cancer: Clinical trial and in vitro correlates

Treatment of patients with relapsed small-cell lung cancer (SCLC) has been uniformly unsuccessful. Recently, the combination of etoposide (VP-16) and cisplatin in this setting has been reported to result in up to 50% response rates. We treated 29 patients with relapsed SCLC with this combination and found only a 12% response rate. The discrepancy between our results and those of others is most likely due to differences in prior treatment of the patients, although the effect of dose and schedule modifications are considered. Our patients had received a six-drug regimen over a median of 7 months and had a median drug-free interval before this treatment of only three weeks. Evidence is presented that suggests that this aggressive initial therapy affected both host tolerance to further treatment and the development of tumor resistance at the cellular level.