Between July 13, 2001 and January 13, 2004, 17 patients were enrolled to the Phase I portion of the study. Eligible patients had histologically-proven stages I-IIIB NSCLC, Zubrod performance status 0-1, ≤ 5% weight loss within the past 6 months, a forced expiratory volume at 1 second of ≥ 1 liter, and atelectasis, if present, must be less than one lung. Based on conformal treatment planning, the volume of lung at or exceeding 20 Gy (V20) must have been ≤ 30%, the mean esophagus dose ≤ 34 Gy, and the volume of esophagus exceeding 55Gy (V55) ≤ 30%. Exclusion criteria included prior radiation therapy to the thorax, prior chemotherapy or biologic cancer therapy for lung cancer within the past 2 years, prior or concurrent malignancy (except non-melanoma skin cancer) unless disease-free for one or more years, supraclavicular lymph node metastasis, pleural or pericardial effusions, and superior vena cava syndrome. The metastatic workup included pulmonary function testing, chest x-ray, computed tomography (CT) of the chest and upper abdomen, either magnetic resonance imaging or CT of the brain, a bone scan, complete blood counts, electrolytes, alkaline phosphatase, and liver function tests. Positron emission tomography was not required as it was not routine at the outset of the study, though 7 out of 17 (41%) patients were staged with a diagnostic FDG-PET scan.
Treatment consisted of fractionated radiation therapy given with concurrent weekly chemotherapy consisting of paclitaxel 50 mg/m2 over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 followed by carboplatin AUC=2 over 30 minutes days 1, 8, 15, 22, 29, 36, and 43. Adjuvant systemic chemotherapy was optional following completion of radiation therapy, though no patients received it.
Radiation therapy was initially planned to be given by a dose escalation design using increasing doses per fraction (75.25 Gy at 2.15 Gy per fraction, 80.5 Gy at 2.3 Gy per fraction, 79.5 Gy at 2.65 Gy per fraction, and 75Gy at 3 Gy per fraction) (). However, due to excessive toxicity at dose level 1 (75.25 Gy at 2.15 Gy per fraction), an amendment was made to the protocol in January 2003 and Cohort 2 was de-escalated to 74 Gy at 2 Gy per fraction and this dose opened to accrual in February 2003 (). The trial was closed after accrual to Phase I was completed in January 2004, and reopened in August 2004 for Phase II accrual at the 74 Gy dose level. Three-dimensional conformal radiation therapy was required. Radiation doses were prescribed to the isocenter using water-based calculations. Gross tumor volume (GTV) was defined as the primary tumor and any lymph nodes exceeding 1 cm in greatest diameter. The GTV was expanded by 1 to 1.5 cm to achieve the planning target volume (PTV). No clinical target volume (CTV) was specifically delineated. Elective nodal volumes were not included within the PTV. The protocol was designed to be stringent with respect to radiation dose to the normal lung and esophagus. Patients must have met V20 ≤ 30%, mean esophagus dose ≤ 34 Gy, and esophageal V55 ≤ 30%. V20 was calculated by using total lung minus PTV as the normal lung volume. The radiation treatment plan for each patient was stored centrally at the Image-Guided Therapy Center (ITC) and scored for compliance by the principal investigator.