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

Abstract

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.