Phase II Study of 3-D Conformal Radiotherapy and Concurrent MVP (Mitomycin-C+Vinblastine+Cisplatin) Chemotherapy for Unresectable Non-Small Cell Lung Cancer

ABSTRACT

PURPOSE: To evaluate the feasibility, treatment outcome, and toxicity of hyperfractionated 3-D conformal radiotherapy and concurrent MVP chemotherapy in locally advanced, unresectable stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From August 1993 to December 1996, 161 patients with unresectable stage III NSCLC were entered into this trial, and 146 (91%) completed the treatment. Hyperfractionated radiotherapy was given to a total dose of 64.8~70 Gy (1.2 Gy/fx, bid) with 2 cycles of concurrent MVP (Mitomycin-C 6 mg/m2 d2 and d29, Vinblastine 6 mg/m2 d2 and d 29, and Cisplatin 60 mg/m2 d1 and d28) chemotherapy. Of the 146 patients who completed the treatment, 78 received noncoplanar 3D conformal radiotherapy using 4~6 fields and 17 received coplanar-segmented conformal radiotherapy. Clinical tumor response was assessed one month after the completion of radiotherapy by a computerized tomography (CT) scan. Toxicity was graded using the SWOG criteria. Normal tissue complication probability (NTCP) for the lung was calculated to determine any the correlation with radiation pneumonitis. Nineteen (13%) had stage IIIa and 127 (87%) had IIIb disease, which included 16 patients with pleural effusion and 20 with supraclavicular lymph node metastasis. RESULTS: The response rate was 75%, composed of 22% complete responders and 53% partial responders. With a minimum follow up of 45 months, overall survival was 51.2% at 1 year, 25.1% at 2 years and 14.8% at 5 years; median survival was 12 months. Patients achieving complete response (n=32) had a 2-year overall survival of 49.8% and a 5 year survival of 39.2%, compared to 22.5% and 11.4% survival for the partial responders (n=78) (p=0.0001). Actuarial local progression free survivals for all patients were 65% at 1 year, 42% at 2 years and 36% at 4 years, and actuarial distant free survival was 58% at 1 year, 49% at 2 years and 41% at 5 years. Severe weight loss (more than 10%) occurred in 20 of the 146 patients (13.7%) during treatment, 42 patients (29%) developed radiation pneumonitis, 29 had grade 1 and 13 showed grade 2. The average NTCP value of the patients who showed radiation pneumonitis was significantly higher than that of patients without pneumonitis (66.0% vs. 26.4%). Four patients died of treatment related toxicity. CONCLUSION: Hyperfractionated 3D conformal radiotherapy and concurrent chemotherapy, as described here, is a well tolerate regimen with acceptable toxicity. More effective treatment scheme will be required to improve on local disease control and overall survival.