Clinical efficacy and safety of randomized phase 2 trial of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma

Abstract

Objective To evaluate the clinical efficacy and toxicity of concurrent pemetrexed-cisplatin (PP) or docetaxel-cisplatin (DP) with intensity-modulated radiation therapy (IMRT) in patients with stage ⅠV lung adenocarcinoma. Methods Stage IV lung adenocarcinoma patients with unknown EGFR mutation status or wild-type admitted to Guizhou Cancer Hospital from 2011 to 2016 were randomly assigned into the PP (n=50) and DP groups (n=51). All patients received concurrent IMRT of the chest at a prescription dose of 60-70 Gy. Primary endpoint was 1-year survival rate, and secondary endpoint was acute toxicity. Results The overall response rate was 68.0% and 72.5% in the PP and DP groups (χ2=0.250, P=0.617). The median survival time was 19.6 months (95%CI 13.9-25.3) versus 12.1 months (95%CI 10.7-13.5) in the PP and DP groups. The 1-, 2-and 3-year overall survival rates were 72.0% versus 52.9%, 28.0% versus 17.6%, and 16.0% versus 13. 7%, respectively in the PP and DP groups (P=0.049). In the PP and DP groups, the incidence of grade 3-4 leukopenia was declined by 48% and 63%(P=0.098), and the incidence of grade 3-4 neutropenia was decreased by 34% and 65%(P=0.002), the incidence of grade 3-4 anemia was reduced by 38% and 10%(P=0.024), and the incidence of grade 3-4 thrombocytopenia was declined by 40% and 14%(P=0.003). The incidence rate of grade 2 pneumonitis (P=0.625) and grade 3 esophagitis (P=0.484) were similar in both groups. No patients experienced ≥grade 3 pneumonitis or ≥ grade 4 radiation esophagitis. Conclusions Pemetrexed-cisplatin combined with chemoradiotherapy yields higher clinical efficacy compared with docetaxel-cisplatin plus concurrent chemoradiation in the treatment of stage ⅠV lung adenocarcinoma. The incidence of radiation pneumonitis and esophagitis is similar. The incidence and severity of hematological toxicity does not significantly differ between two groups. Treatment-related toxicity is tolerable in both groups. Clinical Trial Registration Chinese Clinical Trial Registry (ChiCTR-TRC-13004184). Key words: Stage IV lung adenocarcinoma; Radiotherapy; Intensity-Modulated; Pemetrexed; Docetaxel; Phase 2 trial