Phase I trial of intravenous carboplatin added to oral etoposide and oral cyclophosphamide for stage IV non-small cell lung cancer.

The combination of oral etoposide and oral cyclophosphamide is an active and easily administered outpatient regimen for non-small cell lung cancer with leukopenia as the most common severe toxicity. To maintain ease of outpatient administration and to take advantage of a differing dose-limiting toxicity, we attempted to add escalating doses of intravenous carboplatin to full-dose oral etoposide and oral cyclophosphamide for chemotherapy-naive patients with Stage IV non-small cell lung cancer. The first 4 patients received etoposide and cyclophosphamide (each at 50 mg PO BID Days 1-12 every 28 days) with intravenous carboplatin on Day 1 at a dose calculated by the Calvert formula to achieve AUC 4. With this regimen dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was noted. An additional 3 patients therefore received etoposide and cyclophosphamide at a 25% reduced dose (each at 50 mg PO BID Days 1-9 every 28 days) with intravenous carboplatin on Day 1 at a dose calculated to achieve AUC 4. Dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was again noted. One patient achieved a partial response maintained for 6 months. However potentiation of leukopenia/granulocytopenia by carboplatin prevents full-dose use of either cyclophosphamide and etoposide or of carboplatin in this regimen.