Phase I study of hyperfractionated accelerated radiotherapy and escalating doses of daily cisplatin for patients with locally advanced non-small-cell lung cancer

Purpose: To determine the maximal tolerated dose of daily cisplatin (CDDP) administered during an aggressive program of hyperfractionated accelerated radiotherapy (t.i.d. RT) for locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty patients with Stage III NSCLC were treated with RT administered three times daily and escalating doses of concurrent daily CDDP. The t.i.d. RT was delivered on 12 weekdays as follows: a total of 57.6 Gy was administered using 10-MV X-rays in 1.5-Gy fractions at 8 am and 4 pm and 1.8-Gy fractions at 12 pm. AP-PA fields were used in the morning and afternoon, and oblique fields, which included no spinal cord, were used at 12 pm. The first group of 5 patients was not given CDDP, the second group of 5 patients received 5 mg/m(2) of CDDP, and the last group of 10 patients received 7.5 mg/m(2). Toxicity was evaluated using the National Cancer Institute Common Toxicity Criteria. Results: The first group of 5 patients received no CDDP. One of these patients developed both Grade 3 esophagitis and Grade 3 pneumonitis. The second group of 5 patients received 5 mg/m(2) of CDDP. One of these patients developed Grade 3 esophagitis. The last group of 10 patients received 7.5 mg/m(2) of CDDP. Four of these patients developed Grade 3 toxicity and one developed Grade 4 toxicity. None of the patients died as a result of toxicity. The median survival for the 20 patients was 19 months. The tumor response and patterns of failure were also evaluated. Conclusion: This study was performed to determine the maximal tolerated dose of CDDP when administered daily during an aggressive program of t.i.d. RT. A dose of 7.5 mg/m(2) daily was determined to be the maximal tolerated dose, because this dose caused Grade 3 or 4 toxicity in 50% of the patients who received it. (C) 2002 Elsevier Science Inc.