Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non–Small-Cell Lung Cancer

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To determine in a Phase I study the maximum tolerated dose of weekly gemcitabine concurrent with radiotherapy in locally advanced non-small-cell lung cancer (NSCLC), as well as the relationship between the volume of the esophagus irradiated and severe esophagitis. Twenty-one patients with Stage III NSCLC received gemcitabine initially at 150 mg/m(2)/wk over 7 weeks concurrently with chest radiotherapy to 63 Gy in 34 fractions. The first 9 patients underwent treatment with two-dimensional (2D) radiotherapy; the remaining 12 patients, with three-dimensional conformal radiotherapy (3D-CRT) and target volume reduced to clinically apparent disease. Consolidation was 4 cycles of gemcitabine at 1000 mg/m(2)/wk and cisplatin 60 mg/m(2). In the 2D group, the dose-limiting toxicity, Grade 3 esophagitis, occurred in 3 of 6 patients in the 150-mg/m(2)/wk cohort and 2 of 3 patients in the 125-mg/m(2)/wk cohort. No cases of Grade 3 esophagitis occurred at these doses in the 3D group. At gemcitabine 190 mg/m(2)/wk, 2 of 6 patients in the 3D cohort had Grade 3 esophagitis. The mean percentages of esophagus irradiated to 60 Gy were 68% in the 2D cohort and 18% in the 3D cohort. We could not escalate the dose of gemcitabine with concurrent radiotherapy when using 2D planning because of severe acute esophagitis. However, we could escalate the dose of gemcitabine to 190 mg/m(2)/wk when using 3D planning. The Phase II dose is 150 mg/m(2)/wk. Three-dimensional CRT permitted the use of higher doses of gemcitabine.