S-1 Plus Cisplatin Combination Chemotherapy in Patients with Advanced Non–Small Cell Lung Cancer

Abstract

Purpose: To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients.Experimental Design: In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m 2 twice a day for 21 consecutive days while cisplatin (60 mg/m 2 ) was administered intravenously on day 8. This schedule was repeated every 5 weeks.Results: Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1-12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34 -61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%).Conclusions: S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

“…Therefore, it is important to inhibit the DPD activity to improve the responsiveness to 5-FU against DPD-positive NSCLCs. Recently, S-1 (a combination of tegafur, gimeracil, and oteracil potassium, Taiho) has been developed for clinical use (Chu et al, 2004;Ichinose et al, 2004). Gimeracil used in S-1 is a stronger inhibitor for the intratumoural DPD activity than uracil used in UFT.…”

Prospective exploratory study of gemcitabine and S-1 against elderly patients with advanced non-small cell lung cancer

“…Tegafur, a prodrug of 5-fluorouracil (5-FU), is gradually converted to 5-FU, and is rapidly catabolized by dihydropyrimidine dehydrogenase in the liver. In several studies, S-1 has been reported to actively reduce tumor growth in various human cancers, and a combination of platinum-based regimens with S-1 has been the standard treatment regimen against advanced NSCLC (7)(8)(9)(10)(11)(12). Gemcitabine, an anticancer drug that structurally resembles cytosine arabinoside, has been demonstrated to exhibit high anti-tumor activity with minimal adverse effects (13).…”

High Expression of Dihydropyrimidine Dehydrogenase in Lung Adenocarcinoma is Associated With Mutations in Epidermal Growth Factor Receptor: Implications for the Treatment of Non–Small-Cell Lung Cancer Using 5-Fluorouracil

“…The phase II and phase III trials of S-1 plus platinum documented that S-1 is effective against both adenocarcinoma (ADC) and squamous cell carcinoma (SQCC), suggesting that S-1 is a valid treatment option. 6,7 EGFR mutation status is well known as a predictor of response to treatment by EGFR tyrosine kinase inhibitor (EGFR-TKI) and as the target of EGFR-TKIs. [8][9][10] In 2007, Suehisa and colleagues reported that adjuvant chemotherapy with uraciltegafur significantly prolonged survival rates among patients with EGFR wild-type adenocarcinoma but not among patients with EGFR mutant tumors.…”