Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma.

Systemic chemotherapy is the standard treatment modality for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status. Recent years, there is increasing evidence showed that selected patients with stage IV disease could benefit from aggressive thoracic radiotherapy. Either pemetrexed or docetaxel, combined with cisplatin, can be used for patients with stage IV lung adenocarcinoma. However, no prospective trials have confirmed that Pem-Cis was superior to Doc-Cis in lung adenocarcinoma. In this randomized phase 2 trial, we evaluated survival outcomes, and toxicity of Pemetrexed-Cisplatin (arm A) or Docetaxel-Cisplatin (arm B) with concurrent IMRT to the primary tumor for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status. Totally, 101 patients were randomly assigned (50 in arm A and 51 in arm B). Using an intention-to-treat analysis, one-year survival rates were 72.0% and 52.9%, respectively (P=0.020). Progression-free survival was also significantly improved in the arm A (median, 12.6 v 7.5 months, P=0.013). The incidence and severity of acute pneumonitis and esophagitis was similar between two arms. Although more of grade 3 or 4 anemia and thrombocytopenia in arm A, and higher rates grade 3 or 4 neutropenia, and leukopenia were observed in arm B. Pem-Cis first-line chemotherapy with concurrent radiation therapy for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status represents a potential treatment option with acceptable toxicity and high overall survival rates.