Oral fluorouracil vs vinorelbine plus cisplatin as adjuvant chemotherapy for stage II‐IIIA non‐small cell lung cancer: Propensity score‐matched and instrumental variable analyses

BACKGROUND: Adjuvant chemotherapy with vinorelbine plus cisplatin (VNR/CDDP) is a standard regimen for treatment of postoperative stage II‐IIIA non‐small cell lung cancer (NSCLC). However, oral fluorouracil offers a feasible alternative adjuvant chemotherapeutic regimen. We compared the prognoses of patients with NSCLC treated with adjuvant chemotherapy with either VNR/CDDP or oral fluorouracil. METHODS: We identified patients with stage II‐IIIA NSCLC who underwent lung surgery followed by adjuvant chemotherapy with VNR/CDDP (n = 384) or oral fluorouracil (n = 268) between July 2010 and March 2015, using the national Japanese inpatient and outpatient Diagnosis Procedure Combination database. We compared recurrence‐free survival between the groups by multivariable Cox regression analysis for one‐to‐one propensity score‐matched patients and by instrumental variable analysis. RESULTS: Younger patients and patients with positive N2 nodes were more likely to receive VNR/CDDP, while older patients and those with T3N0 classification were more likely to receive oral fluorouracil. Among 172 pairs of propensity‐matched patients, time to adjuvant chemotherapy was shorter for oral fluorouracil compared with VNR/CDDP. Oral fluorouracil was also significantly associated with improved recurrence‐free survival compared with VNR/CDDP, according to multivariable Cox regression analysis (hazard ratio, 0.41; 95% confidence interval, 0.26‐0.64). Instrumental variable analysis showed a similar relationship (hazard ratio, 0.19; 95% confidence interval, 0.038‐0.92). CONCLUSIONS: On a large nationwide cohort, adjuvant chemotherapy with oral fluorouracil prolonged recurrence‐free survival in patients with postoperative stage II‐IIIA NSCLC, compared with VNR/CDDP. Oral fluorouracil may thus be a useful alternative to VNR/CDDP for the adjuvant treatment of these patients.