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Background: Oral adjuvant chemotherapy without hospitalization might reduce the physiological and psychological burden on patients if effectiveness could be guaranteed. We conducted a multicenter feasibility study using S-1, an oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy in patients with curatively resected pathologically stage IB-IIIA non-small-cell lung cancer. Patients and Methods: Adjuvant chemotherapy comprised 8 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg per day. Fifty-one patients from 7 institutions were enrolled in this pilot study, from June 2005 to March 2007. The primary end point was the completion rate of scheduled adjuvant chemotherapy. Secondary end points were the incidence and grade of adverse reactions. Results: Fifty patients were eligible. The completion rate for the planned 8 courses of S-1 administration was 72.0% (36 patients). Total percentage administration amount was 71.1%. Grade 3 adverse reactions such as neutropenia (4.0%), anorexia (4.0%), thrombopenia (2.0%), anemia (2.0%), elevated total bilirubin (2.0%), hypokalemia (2.0%), nausea (2.0%), and diarrhea (2.0%) were observed, but no grade 4 adverse effects were encountered. Overall and relapse-free survival rates at 3 years were 87.7% and 69.4%, respectively. Conclusions: Postoperative 1-year administration of S-1 seems feasible as oral adjuvant chemotherapy for lung cancer. The oral formulation and low incidence of adverse reactions permit treatment on an outpatient basis. The present study would be reasonable to follow up with a properly powered phase III trial., Clinical Lung Cancer, 13(6), pp.464-469; 2012

PURPOSE The treatment strategy for patients with non–small-cell lung cancer (NSCLC) involving ipsilateral mediastinal lymph nodes is still controversial. We performed a phase II feasibility study of induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC. PATIENTS AND METHODS Patients with mediastinoscopy- positive stage IIIA N2 NSCLC received 2 cycles of cisplatin 80 mg/m2, vinorelbine 25 mg/m2, and mitomycin-C 8 mg/m2. Patients without progressive disease underwent thoracotomy and lobectomy with lymph node dissections 2-4 weeks later. RESULTS From January 2000 to July 2004, 24 eligible patients (15 men, 9 women) were enrolled. Induction chemotherapy was completed as planned in 23 patients (95.8%). Hematological toxicity was the primary grade 3/4 toxicity. Twelve (50%) patients achieved a partial response. Twenty-three patients underwent surgical resection, and complete resection was achieved in 22 patients (95.7%). There were no surgery-related deaths. Pathologic complete response in metastatic lymph nodes was achieved in 5 patients. With a median follow-up of 5.4 years (range, 2.88-7.7 years), the estimated 5-year survival was 51.8% (95% CI, 41.3-62.3) and progression-free survival was 46.6% (95% CI, 36–57.2). CONCLUSION Induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC was feasible and associated with high response to lymph node metastasis and good survival.

Dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), and thymidylate synthase (TS) levels correlate with sensitivity and resistance to 5-fluorouracil (5-FU). Few data are available on these enzymes in pulmonary neuroendocrine carcinoma, because 5-FU appears to have minimal effect on such carcinomas.This study investigated 5-FU-related enzymes in large-cell neuroendocrine carcinoma (LCNEC; n = 31) and small-cell lung carcinoma (SCLC; n = 15), comparing expression levels with epithelial carcinomas including adenocarcinoma (ADC; n = 34) and squamous cell carcinoma (SCC; n = 13) obtained from 93 patients with primary lung tumors. Levels of 5-FU-related enzyme mRNA were analyzed by laser capture microdissection, compared with immunohistochemical findings and correlated with clinicopathologic factors.LCNEC and SCLC showed significantly higher TS and OPRT mRNA levels than ADC. SCLC exhibited significantly higher TS mRNA levels than LCNEC (P = .002). LCNEC displayed significantly lower DPD mRNA levels than ADC (P.001), with a similar tendency in SCLC. SCC showed significantly lower DPD (P.01) and higher OPRT (P.001) mRNA levels than ADC. When we divide the data by pathology into epithelial carcinoma and neuroendocrine carcinoma, malignant potentials and prognoses correlated with mRNA levels in epithelial carcinoma, but not in neuroendocrine carcinoma. Immunohistochemically, neuroendocrine carcinomas were immunonegative for DPD. A significant correlation was found between enzymatic mRNA and protein expression for DPD (R = .500) and a weak correlation was observed for TS (R = .294).Neuroendocrine carcinomas show characteristic patterns of expression for 5-FU-related enzymes, including low DPD mRNA and protein level and high TS mRNA level compared with adenocarcinomas. These results partially explain why 5-FU-based chemotherapy shows minimal efficacy against SCLC. Conversely, clinicopathological data and survival analysis indicates that 5-FU-related enzymes themselves might not affect the malignant potential of neuroendocrine carcinoma. Expressional differences in 5-FU-related enzymes among pathologies may provide valuable information for tailor-made chemotherapy.