DAILY LOW-DOSE CISPLATIN PLUS CONCURRENT HIGH-DOSE THORACIC IRRADIATION IN LOCALLY ADVANCED UNRESECTABLE NON-SMALL-CELL LUNG-CANCER - RESULTS OF A PHASE-II SOUTHWEST-ONCOLOGY-GROUP STUDY

Purpose: This single-arm phase II trial was designed to evaluate the e fficacy and toxicity of continuous course, high-dose thoracic irradiat ion (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced u nresectable non-small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of c isplatin. Patients and Methods: Sixty-five patients from 21 participat ing institutions were entered onto the study between April 1989 and Ma y 1991. Protocol therapy consisted of daily intravenous (IV) cisplatin (5 mg/m(2)) plus concurrent continuous-course RT (61 Gy over 61/2 wee ks) both delivered Monday through Friday each week. After a 3- to 4-we ek rest period, this was followed by three 28-day cycles of cisplatin at 100 mg/m(2) or subsequently 50 mg/m(2) administered IV on days 1 an d 8 of each cycle. Results: Sixty-four patients were eligible; the maj ority had unresectable stage IIIa (36%) or IIIb (55%) NSCLC. The remai ning 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is de monstrated by the fact that only five patients (8%) were unable to com plete daily cisplatin and RT because of toxicity. Esophagitis (16%), l eukopenia (14%), nausea (8%), and vomiting (6%) were the most common s evere (grade 3) toxicities. There was only one life-threatening toxici ty (grade 4 nausea) and no treatment related deaths. The objective res ponse rate was 39%, and six patients (9%) achieved a radiographic comp lete response (CR). The median survival duration for all patients was 14 months, and the 1- and 2-year actuarial survival rates were 56% and 24%, respectively. For stage IIIa patients, the median survival durat ion and 2-year survival rate were 17 months and 38%, as compared with 10 months and 14% for stage IIIb patients, respectively. Conclusion: D aily low-dose cisplatin plus concurrent high-dose continuous-course RT is a well-tolerated outpatient regimen. The survival results are enco uraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum anal ogs with RT. (C) 1994 by American Society of Clinical Oncology.