PHASE-I TRIAL OF INTRAVENOUS CARBOPLATIN ADDED TO ORAL ETOPOSIDE AND ORAL CYCLOPHOSPHAMIDE FOR STAGE-IV NONSMALL CELL LUNG-CANCER

The combination of oral etoposide and oral cyclophosphamide is an acti ve 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 differin g dose-limiting toxicity, we attempted to add escalating doses of intr avenous carboplatin to full-dose oral etoposide and oral cyclophospham ide 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 carbopl atin on Day 1 at a dose calculated by the Calvert formula to achieve A UC 4. With this regimen dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was noted. An additional 3 patients the refore received etoposide and cyclophosphamide at a 25% reduced dose ( each at 50 mg PO BID Days 1-9 every 28 days) with intravenous carbopla tin on Day 1 at a dose calculated to achieve AUC 4. Dose-limiting toxi city (2 patients with Grade 4 leukopenia/granulocytopenia) was again n oted. One patient achieved a partial response maintained for 6 months. However potentiation of leukopenia/granulocytopenia by carboplatin pr events full-dose use of either cyclophosphamide and etoposide or of ca rboplatin in this regimen.