Phase I results of RTOG L-0117; a phase I/II dose intensification study using 3DCRT and concurrent chemotherapy for patients with Inoperable NSCLC

Abstract

7063 Background: The standard radiation dose for NSCLC was established by RTOG 7301 as 60 Gy. Local failure rates with this dose remain unacceptably high. Current cooperative group trials continue to use doses of 60–63 Gy in the setting of concurrent chemotherapy. The primary endpoint of the Phase I portion was to establish the maximum tolerated dose (MTD) of radiation therapy, in the setting of concurrent chemotherapy, using 3DCRT for NSCLC. Methods: Eligibility included patients with histologically proven, unresectable Stages I-III NSCLC and a Zubrod perfomance status of 0–1. Weight loss eligibility was ≤10%. Concurrent chemotherapy consisted of paclitaxel 50 mg/m2 and carboplatin AUC=2 given weekly. Radiation dose was to be sequentially intensified by increasing the daily fraction size starting at 75.25 Gy/35 fractions. Interim analysis was planned after the initial 7 patients were enrolled with application of the stopping rule if DLTs occurred in 2 or more patients. Radiation therapy volumes consisted of gross tumor and nodes plus a margin. Elective lymph nodes were not included in the treatment fields. Technical criteria included strict dosimetric constraints on the normal lung (V20 ≤30%) and esophagus (mean dose ≤34 Gy and V55 ≤ 30%) and water-based dose calculations prescribed to the isocenter. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial eight patients were accrued to Arm 1, the trial closed temporarily on September 26, 2002 due to reported toxicity. Two acute treatment-related DLTs were reported: a grade 5 and a grade 3 pneumonitis. Subsequent DLTs since closure of Arm 1 include a grade 3 late pneumonitis and a grade 4 pain toxicity. The protocol was revised to de-escalate the radiotherapy dose (74 Gy/37 fractions). Arm 2 accrued 9 patients. One patient on Arm 2 developed a grade 3 esophagitis. Conclusions: The MTD was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using 3DCRT with concurrent paclitaxel and carboplatin. The Phase II component of RTOG L-0117 remains open to accrual at 74 Gy. No significant financial relationships to disclose.