Adjuvant chemoradiotherapy (CRT) for high-risk gastric cancer (GC) patients: single-center experience using infusional 5-fluorouracil (5FU) and radiotherapy (RT)

Abstract

Gastric cancer represents a major cause of death worldwide [1]. Postoperative CRT is a standard treatment option for fully resected high-risk GC. Adjuvant CRT using bolus 5FU significantly improved overall (OS) and disease-free survival (DFS) versus surgery alone. However, this approach is associated with significant toxicity, poor tolerability and low compliance. Herein, we present our data using a modified infusional 5FU regimen aiming to improve tolerability and toxicity. In this observational study patients included were referred after surgery; they were considered to have highrisk GC and hence received adjuvant CRT. The treatment comprised six cycles of leucovorin: 350 mg iv (d1) and 5FU: 400 mg/m iv-bolus (d1), 2,800 mg/m over 46 h; the third and fourth cycle of chemotherapy given concurrently with RT as follows: total dose of RT 4,500 cGy in 25 fractions of 180 cGy. Sixty-eight patients, median age 59 years with a median follow-up period of 32 months (range, 5–90) were treated, stage IB, 4.4 %; IIA, 7.35 %; IIB, 13 %; IIIA, 11.7 %; IIIB, 30.8 %; IIIC, 32.3 %. Furthermore, in our study, 51.5 % of patients had less than 15 lymph nodes removed. The median DFS and OS were 25.2 and 32 months, respectively. According to the National Cancer Institute Common Toxicity Criteria Classification, Grade III or higher myelotoxicity was neutropenia 16 % and thrombocytopenia 3 %. Grade III or higher nonhematologic toxicity was diarrhea 19 %, vomiting 3 %, stomatitis/esophagitis 8 % and constipation 3 %. There was no grade IV nonhematologic toxicity. Fifty-three patients (78 %) completed the treatment. The US Intergroup 0116 study is the most important trial evaluating the role of CRT in high-risk GC patients [2]. The median DFS and OS were 30 and 40 months, respectively. However, significant toxicity was reported. Overall grade C3 toxicities occurred in 73 % of patients, including high rates of overall hematologic and gastrointestinal toxicity in 54 and 33 % of the patients, respectively. Furthermore, only 63 % of patients completed treatment as planned. In our study, the high incidence of poor prognosis clinical and pathological features, R1 resection in some cases and possible peritoneal disease—not evaluated at diagnosis with staging laparoscopy—likely explains the somewhat lower than expected efficacy. However, both hematologic and gastrointestinal toxicity profiles were satisfactory. Tolerability was acceptable with more than 70 % of the patients receiving the planned cumulative dose of chemotherapy and 75 % completing six cycles. Improved efficacy in this setting does remain a challenge. The addition of combination 5FU-based chemotherapy to adjuvant RT did not improve outcomes in the context of a recent Intergroup randomized trial [3]. Adequate surgery remains one of the most important predictors for better outcome. Despite a relatively short median follow-up and small sample size, these preliminary data suggest that this approach could be an alternative, with favorable toxicity and tolerability in patients with fully resected high-risk GC. The use of infusional 5FU with radiation is recommended in the latest ESMO guidelines. K. Papadimitriou P. Kountourakis (&) D. Papamichael Department of Medical Oncology, B.O. Cyprus Oncology Centre, 32 Acropoleos Ave, 2006 Strovolos, Nicosia, Cyprus e-mail: pantkount@gmail.com