CARBOPLATIN AND SIMULTANEOUS RADIATION IN THE TREATMENT OF STAGE IIIA/B NON-SMALL-CELL LUNG-CANCER

The radiosensitizing properties of carboplatin were investigated in preclinical and clinical studies. In human non-small cell lung cancer (NSCLC) cell lines (EPLC 65 H and LCLC 97 TM 1) combined carboplatin and radiation therapy was superior to chemotherapy or radiotherapy alone, indicating the existence of additive effects for both treatment modalities. In a subsequent clinical phase II trial, escalating doses of carboplatin were given concurrently with radiation to patients with stage IIIA/B NSCLC. Radiotherapy was given in daily doses of 2 Gy, 5 days a week, during weeks 1-3 and 6 and 7. Carboplatin was given on day 1 in weeks 1-3 and 6 and 7. The starting dose level was 100 mg/m2, followed by dose escalations to 120, 130, 140, 150, 160, 180, and 200 mg/m2. Five patients were to be treated at each dose level until intolerable toxicity (World Health Organization grade 3 or 4 leukopenia) occurred in 3 of the 5. To date, 34 patients have been entered into the study. Toxicity was mild and, even at the 180-mg/m2 dose level, no severe myelosuppression was observed. Thus, the maximum tolerated dose of carboplatin has not yet been reached. Preliminary analysis of response and survival shows an overall response rate of 53% and a median survival of 10 months. Patients receiving higher carboplatin doses (140-160 mg/m2) survived longer than patients who received lower doses (100-130 mg/m2). These preliminary results indicate that combination carboplatin and radiation therapy is a well-tolerated, active regimen in patients with locally advanced NSCLC. Splitting carboplatin administration may reduce its hematologic toxicity.