Dose Escalation of Gemcitabine Concomitant With Radiation and Cisplatin for Nonsmall Cell Lung Cancer: A Phase 1-2 Study

The current study was conducted to evaluate the maximum tolerable dose of weekly gemcitabine administered simultaneously with radiation and cisplatin in patients with locally advanced nonsmall cell lung cancer (NSCLC). Patients with stage IIIA/B NSCLC received concurrently 63 grays radiation and 20 mg/m² cisplatin Day 1 to 3 in Weeks 1 and 5, plus weekly gemcitabine at escalating doses (150-700 mg/m²) on Fridays after radiation to avoid radiosensitization. The authors assessed dose-limiting toxicities according to Common Toxicity Criteria. The primary endpoint was maximum tolerated dose (MTD) of gemcitabine. Tumor resectability, survival, and disease-free survival (DFS) were also determined. Forty-two patients were accrued, of whom 95% received radiation and 66% cisplatin as above. Weekly doses of gemcitabine were escalated to 700 mg/m². Grade 3 dysphagia and 1 case of fatal, probably treatment-related pulmonary deterioration established the MTD of gemcitabine at 550 mg/m² weekly. Twenty-five patients underwent surgery, and histopathological complete regression was documented in 26% of these patients. Overall, median actuarial survival and DFS were 23.8 and 12.4 months, respectively. Gemcitabine at doses up to 550 mg/m² weekly can be given simultaneously with radiation and cisplatin to patients with locally advanced NSCLC. Radical resection thereafter is feasible. The impact of this aggressive therapy should be evaluated further.