Efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for locally advanced rectal cancer

Abstract

Preoperative chemoradiotherapy with capecitabine or 5-fluorouracil is a standard treatment for locally advanced rectal cancer (LARC). S-1, a prodrug of 5-fluorouracil, is a candidate for this chemoradiotherapy regimen in Japan; however, treatment outcomes after S-1 treatment alone are not clear. This study aimed to assess the efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for LARC. We retrospectively evaluated 54 LARC patients who underwent preoperative chemoradiotherapy with S-1 alone in our institution between 2005 and 2017. The clinical tumor stage was cT2–3 in 31 patients and cT4 in 23 patients, and lymph node metastases were clinically evident in 31 patients. S-1, at a dose of 80 mg/m2/day, was orally administered during radiotherapy. A total dose of 45–50.4 Gy was delivered in 25–28 fractions (median: 50.4 Gy). Surgical resections were scheduled 6–10 weeks after chemoradiotherapy completion. The 3- and 5-year overall survival rates were 92.4 and 72.8%, respectively, with a median follow-up time of 51 months. The 3- and 5-year local control rates were 96.2 and 85.9%, respectively. A pathological complete response was observed in 7 patients (13.0%) at the time of surgery. Ten patients (18.5%) had grade 3 acute toxicities and 5 patients (9.3%) had grade 3 late toxicities. No grade 4 or 5 toxicities were observed. Preoperative chemoradiotherapy with S-1 alone followed by total mesorectal excision resulted in a low incidence of toxicities and comparable clinical results. Therefore, S-1 alone can be a treatment option for preoperative chemoradiotherapy in LARC patients.

Efficacy and safety of preoperative chemoradiotherapy with S-1 for advanced rectal cancer: a phase II study

“…Grade 3 or higher adverse events were reported in 13.5% of patients [ 20 ], which is comparable to the 7% rate (two events) observed in our study. Imano et al [ 16 ] reported 18.5% of ≥ Grade 3 side effects, which may have been due to the slightly higher radiation dose of 50.4G. Although the preoperative CRT with S-1 plus irinotecan or oxaliplatin revealed higher levels of tumor control than those achieved using CRT with S-1 alone, the incidence of side effects in these reports was higher than 15%, which may be problematic.…”

“…First, similar studies using CRT with S-1 alone have reported pCR rates of 10.8% to 22.2% [ 16 , 20 , 28 ], although there were slight differences among the studies in the regimen used. The pCR rate in our study using CRT with S-1 alone was 11%, which was not higher than that previously reported using CRT with 2 agents, S-1 plus irinotecan or S-1plus oxaliplatin [ 30 – 31 ], although this was the expected favorable level of pCR rate using CRT with a single agent [ 32 ].…”

“…In a report of CRT with S-1 by Hiratsuka et al [ 40 ] on long-term prognosis, the rates of local recurrence, lung metastasis, and liver metastasis were 13.5%, 16.2%, and 2.7%, respectively. In a report by Imano [ 16 ], the rates of local recurrence, lung metastasis, liver metastasis, and distant lymph node metastasis were 11.1%, 16.7%, 7.4%, and 3.7%, respectively. In the present study, the distant metastasis rate five years after surgery was 18% (5/28), which was similar to that previously reported [ 16 , 40 ].…”

“…In a report by Imano [ 16 ], the rates of local recurrence, lung metastasis, liver metastasis, and distant lymph node metastasis were 11.1%, 16.7%, 7.4%, and 3.7%, respectively. In the present study, the distant metastasis rate five years after surgery was 18% (5/28), which was similar to that previously reported [ 16 , 40 ]. And it was the same tendency that lung metastases were most common in 4 out of 5 patients.…”

“…Furthermore, S-1 reportedly has a radiation-sensitizing effect [ 15 ]. Combining radiation therapy and oral agents is a simple approach and S-1, a prodrug of 5FU, may be a candidate for CRT regimen in Japan [ 16 ]. In our previous study, we designed a phase I trial to provide a simple, safe and effective treatment to achieve curative resection and preserve postoperative voiding function in patients with locally advanced rectal cancer, and we demonstrated a feasible prescription dose for preoperative CRT with S-1 [ 17 ].…”