Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience.

Abstract

Pulmonary large cell neuroendocrine carcinomas (LCNEC) are aggressive neoplasms with poor prognosis. The role of neoadjuvant and adjuvant therapies in these tumors remains uncertain. We performed a retrospective review of a prospective database. Kaplan-Meier estimates of overall survival (OS) were determined and compared across prognostic factors using log-rank analysis and the Cox proportional hazards model. One hundred patients with resected LCNEC were identified from 1992 to 2008. Of these, 54% were male and 98% current or former smokers (mean 60.3 pack-years). Twenty-two patients received neoadjuvant platinum chemotherapy with a response rate of 68% (15 of 22). Eighty percent (80 of 100) underwent lobectomy and 11% (11 of 100) pneumonectomy with a 90% (90 of 100) complete resection (R0) rate. Seventy-one percent (71 of 100) were stage I-II, and 20 of 71 received platinum adjuvant chemotherapy. Mean OS was 40 months. Univariate factors associated with decreased OS included male gender (p = 0.007), increasing tumor (T) stage (p = 0.004), and stage III-IV disease (p = 0.04). Stage IB patients fared significantly worse than IA (p = 0.006). Multivariate analyses identified male gender (hazard ratio [HR] 2.3, p = 0.007), comorbid pulmonary disease (HR 2.3, p = 0.012), and pathologic stage (HR = 2.2, p = 0.011) as associated with risk of death. Univariate analysis in stage IB-IIIA completely resected (R0) patients receiving combination platinum-based induction and (or) adjuvant chemotherapy showed a trend toward improved OS (median survival 7.4 vs 2 years, p = 0.052). The LCNEC has a high response rate to platinum-based neoadjuvant chemotherapy. Resected advanced-stage patients receiving combination neoadjuvant and (or) adjuvant chemotherapy may have a survival advantage. These therapies should be considered in resectable patients with LCNEC.