Long-term results of a multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (JACCRO CC-04: SHOGUN Trial)

• Published in: Radiotherapy and oncology 2019-05, Vol.134, p.199-203
• Main Authors: Kondo, Keisaku, Matsusaka, Satoshi, Ishihara, Soichiro, Horie, Hisanaga, Uehara, Keisuke, Oguchi, Masahiko, Murafushi, Keiko, Ueno, Masashi, Mizunuma, Nobuyuki, Shimbo, Taiju, Kato, Daiki, Okuda, Junji, Hashiguchi, Yojiro, Nakazawa, Masanori, Sunami, Eiji, Kawai, Kazushige, Yamashita, Hideomi, Okada, Tohru, Ishikawa, Yuichi, Fujii, Masashi, Nakajima, Toshifusa
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Chemoradiotherapy; Disease-Free Survival; Drug Combinations; Female; Humans; Locally advanced rectal carcinoma; Long-term outcome; Male; Middle Aged; Neoadjuvant rectal (NAR) score; Neoadjuvant Therapy; Neoplasm Staging; Oxaliplatin; Oxaliplatin - administration & dosage; Oxonic Acid - administration & dosage; Preoperative Care - methods; Preoperative chemoradiotherapy; Rectal Neoplasms - pathology; Rectal Neoplasms - surgery; Rectal Neoplasms - therapy; S-1; Tegafur - administration & dosage
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2019.02.006

•Addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment.•We adopted a chemotherapy gap and S-1 in the regimen, and these may have been factors in the excellent results.•This trial showed that CRT with S-1 plus oxaliplatin and the incorporation of a chemotherapy gap in the third week of radiotherapy was feasible and resulted in a high pCR rate without severe toxicity and excellent loco-regional control. The study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study. Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m2/day on days 1–5, 8–12, 22–26, and 29–33) and infusional oxaliplatin (60 mg/m2/day on days 1, 8, 22, 29) plus radiotherapy (1.8 Gy/day, total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity. Forty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3 months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6 months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively. The study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control.