Phase II trial of S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer

Abstract

BACKGROUND: To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC). METHODS: Eligible patients were 20 -74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0 -1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m À2 on day 1) and S-1 (orally at 40 mg m À2 per dose, b.i.d., on days 1 -14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions. RESULTS: Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1 -96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progressionfree survival was 12.0 months and median overall survival was 33.1 months. The 1-and 2-year survival rates were 89.5 and 56%, respectively. CONCLUSIONS: This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities.

Combined therapy with a thymidylate synthase-inhibiting vector and S-1 has effective antitumor activity against 5-FU-resistant tumors

“…Regarding the in vivo experiments, we used S-1 for the 5-FU treatment. Recently, S-1 has been developed for clinical use (16)(17)(18). Many experimental and clinical studies have revealed that the responsiveness to 5-FU is also associated with the intratumoral expression of dihydropyrimidine dehydrogenase (DPD) (8).…”

“…Consequently, the combined treatment with the adenoviral vector expressing shRNA targeting TS and 5-FU has effective antitumor activity against 5-FU-resistant tumor cells in vitro. Finally, the combined treatment with the TS-inhibiting adenoviral vector and an oral 5-FU-derived agent S-1 (a combination of tegafur, gimeracil and oteracil potassium) (16)(17)(18) was found to have effective antitumor activity against 5-FU-resistant tumor xenografts.…”

S-1-containing chemotherapy for patients with non-small-cell lung cancer: A population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group

“…The non-inferiority of S-1/CBDCA compared with CBDCA/paclitaxel was confirmed for OS (MST, 15.2 vs. 13.3 months, respectively) (20). As a chemoradiotherapy treatment, two phase II trials of S-1 and CDDP combined with concurrent thoracic radiotherapy were evaluated in patients with locally advanced NSCLC (6,21). The RR, PFS and OS of the trials were 82%, 20 months, and not reached at a follow-up time, and 88%, 12 months and 33.1 months, respectively (6,21).…”

“…S-1 was shown to produce an active response as a single agent for metastatic NSCLC with minimal toxicity (2,3). S-1 has been launched for use as a first-line chemotherapy (4) and a second or third-line chemotherapy (5) in advanced stages of the disease, and chemoradiotherapy for stage III (6).…”

Clinical development of S-1 for non-small cell lung cancer: a Japanese perspective

“…In the first trial conducted by the WJTOG, there was a high response rate of 82% and a median PFS of 20 months; median OS was not reached at a follow-up time range from 24 to 37 months . Another trial of similar schedule and dose that was conducted during almost the same period showed an ORR of 88%, median PFS of 12 months, and a MST of 33.1 months, whereas the median followup time was 25 months, ranging from 12 to 38 months [Ohyanagi et al 2009]. Chemotherapy combined with TRT using systemic doses of S-1 and CDDP has the advantage of eradicating occult distant metastases.…”