Phase I study of postoperative radiotherapy concurrent with S-1 in patients with gastric cancer

Abstract

Postoperative chemoradiotherapy (CRT) with concurrent 5-fluorouracil is the standard care for gastric cancer patients after curative surgery. The previous studies revealed that the subgroup of patients with high recurrence risk would benefit most from adjuvant CRT. S-1, a novel oral fluorouracil, has showed very effective in metastatic gastric cancer and became the standard option for gastric cancer with D2 dissection. The safety and dosage of S-1 combined with postoperative radiotherapy have not yet been evaluated. This study is to determine the maximum tolerate dose (MTD) and dose-limiting toxicity (DLT) of S-1 given concurrently with postoperative high-dose radiotherapy in gastric cancer. Patients with more advanced stage (pT4 and/or pN+) after R0 resection were recruited. Eligible patients received one cycle standard SOX (S-1 plus oxaliplatin) chemotherapy, then S-1 monotherapy with concurrent radiotherapy for 6 weeks, followed by additional three cycles of SOX. During the concurrent CRT, S-1 was administered on every radiotherapy treatment day according to a predefined dose-escalation schedule. Radiotherapy (3D-RT or IMRT) was given to a total dose of 50.4 Gy in 28 fractions. DLT was defined as grade 3 or 4 hematologic and non-hematologic toxicity. From March 2011 to October 2012, 21 patients were enrolled at five dose levels: 40 (n = 3), 50 (n = 3), 60 (n = 6), 70 (n = 6) and 80 mg/m(2)/day (n = 3). D2-dissection was performed in 18 patients (85.7 %) and 15 patients (71.4 %) had stage III disease. The most common dose-related toxicity was anorexia, nausea and vomiting, fatigue and leucopenia. DLT was occurred in one patient at 60 mg/m(2)/day (grade 3 fatigue), one patient at 70 mg/m(2)/day (grade 3 vomiting and anorexia), two patients at 80 mg/m(2)/day (one with grade 3 vomiting and anorexia; another with grade 3 febrile leucopenia). Four patients did not complete CRT as planned. Overall, this phase I study demonstrated that postoperative CRT with daily S-1 was feasible in gastric cancer and the MTD of S-1 concurrent with radiotherapy was 70 mg/m(2)/day. This S-1-based postoperative CRT will be investigated in a multicenter phase III study in West China.

The prognostic value of lymph node ratio for local advanced gastric cancer patients with adjuvant chemoradiotherapy after D2 gastrectomy

“…Besides, the specific standard initiation time, duration and dosage of chemotherapeutic agents and radiotherapy were based on our previous trials design. [ 7 – 9 ]…”

Metastasis of lower gingival squamous cell carcinoma to buccinator lymph node: case report and review of the literature

“…A preclinical study suggested that S-1 enhanced sensitivity to radiotherapy [21]. In clinical settings, moreover, the feasibility and efficacy of radiotherapy concurrent with S-1 were demonstrated in some cancers including oral [6], esophageal [22], and gastric cancer [23]. For these reasons, we selected S-1 as a substitute.…”

Between evidence and new perspectives on the current state of the multimodal approach to gastric cancer: Is there still a role for radiation therapy?

“…Nevertheless, this drug is not available in Western countries. In some recent studies, S-1 was administered concomitantly to RT, alone[ 48 - 50 ] or in combination with cisplatin, both in a preoperative and postoperative setting[ 51 , 52 ]. No excessive toxicities and encouraging outcomes were reported, and an MTD ranging between 70 and 80 mg/m 2 was identified.…”