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 efficacy and toxicity of continuous-course, high-dose thoracic irradiation (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced unresectable non- small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of cisplatin. Patients and Methods: Sixty-five patients from 21 participating institutions were entered onto the study between April 1989 and May 1991. Protocol therapy consisted of daily intravenous (IV) cisplatin (5 mg/m²) plus concurrent continuous- course RT (61 Gy over 6 1/2 weeks) both delivered Monday through Friday each week. After a 3- to 4-week rest period, this was followed by three 28-day cycles of cisplatin at 100 mg/m² or subsequently 50 mg/m² administered IV on days 1 and 8 of each cycle. Results: Sixty-four patients were eligible; the majority had unresectable stage IIIa (36%) or IIIb (55%) NSCLC. The remaining 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is demonstrated by the fact that only five patients (8%) were unable to complete daily cisplatin and RT because of toxicity. Esophagitis (16%), leukopenia (14%), nausea (8%), and vomiting (6%) were the most common severe (grade 3) toxicities. There was only one life-threatening toxicity (grade 4 nausea) and no treatment-related deaths. The objective response rate was 39%, and six patients (9%) achieved a radiographic complete 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 duration and 2-year survival rate were 17 months and 38%, as compared with 10 months and 14% for stage IIIb patients, respectively. Conclusion: Daily low-dose cisplatin plus concurrent high-dose continuous-course RT is a well-tolerated outpatient regimen. The survival results are encouraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum analogs with RT.