Platinum/oral etoposide therapy in non-small cell lung cancer

Encouraging response rates have been observed with long-term daily administration of oral etoposide to treat lung cancer. Reasons why EP (etoposide/cisplatin) has been used to treat non-small cell lung cancer (NSCLC), despite the fact that etoposide has demonstrated only a modest degree of activity against this disease, are preclinical suggestions of cisplatin/etoposide synergism and successful results for the combination in treating small cell lung cancer (SCLC). We evaluated a long-term daily oral etoposide regimen in combination with cisplatin for NSCLC. One course consisted of cisplatin on day 1 and etoposide from day 1 through day 21. The course was repeated, beginning at day 29. We concluded that the maximum tolerated dose in this schedule was 50 mg/m2/day oral etoposide for 21 days plus 80 mg/m2 intravenous (i.v.) cisplatin on day 1. The major dose-limiting toxic effect was myelosuppression, and mucositis was also significant in some patients. During this phase I study of 22 patients (18 evaluable), we observed partial responses (PRs) in 4 patients, 1 each with uterine cancer and SCLC, and 2 with squamous cell lung cancers. We then designed a phase II pilot study in patients with advanced NSCLC. The recommended treatment schedule is 80 mg/m2 i.v. cisplatin on day 1 plus 40 mg/m2/day oral etoposide for 21 consecutive days. Of the 13 evaluable patients, PRs were observed in 4 (30.8%), in 2 patients with adenocarcinoma and 2 with squamous cell carcinoma. None of the side effects were severe or life-threatening. Nearly all of the projected doses were given, with delays of 7-10 days. In this pilot phase II study, the response rate of advanced NSCLC was above 30%. Future studies should combine long-term administration of oral etoposide with radiation therapy or surgery to treat stage III NSCLC.