Results of a phase I dose-escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma.

BACKGROUND: The objective of this study was to report the results of a Phase I dose-escalation study using three-dimensional conformal radiation therapy (3D-CRT) for the treatment of patients with nonsmall cell lung carcinoma (NSCLC).
METHODS: Between 1991 and 2003, 104 patients were enrolled for 3D-CRT at Memorial Sloan-Kettering Cancer Center. The median patient age was 69 years. Twenty-eight percent of patients had Stage I-II NSCLC, 33% of patients had Stage IIIA NSCLC, 32% of patients had Stage IIIB NSCLC, and 6% of patients had recurrent NSCLC. Induction chemotherapy was received by 16% of patients. Radiation was delivered in daily fractions of 1.8 grays (Gy) for doses < or = 81.0 Gy and in daily fractions of 2.0 Gy for higher doses. Accrual at a dose level was complete when 10 patients received the intended dose without unacceptable acute morbidity.
RESULTS: After an incident of fatal acute radiation pneumonitis at the starting dose of 70.2 Gy, the protocol was modified to limit normal tissue complication probabilities (NTCP) to < 25%. The dose was then escalated from 70.2 Gy, to 75.6 Gy, 81.0 Gy, and 84.0 Gy, with at least 10 patients treated at each dose level. Unacceptable pulmonary toxicity occurred at 90.0 Gy. Subsequently, another 10 patients were accrued at the 84.0 Gy level with acceptable toxicity. Thus, 84.0 Gy was the maximum tolerated dose (MTD). The crude late pulmonary toxicity rate was 7%, the 2-year local control rate was 52%, the disease-free survival rate was 33%, and the overall survival rate was 40%. The median survival was 21.1 months. Overall survival was improved significantly in patients who received > or = 80.0 Gy.
CONCLUSIONS: The MTD of 3D-CRT for NSCLC with an NTCP constraint of 25% was 84.0 Gy in the current study. There was a suggestion of improved survival in patients who received 80.0 Gy.