Journal of Cancer Research and Therapeutics

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 12  |  Issue : 5  |  Page : 54--56

S-1 combined with cisplatin chemotherapy for advanced gastric cancer


Chen Weidong, Xia Lijun 
 Department of Clinical Pharmacy, Lishui People's Hospital of Zhejiang Province, Lishui 323000, PR China

Correspondence Address:
Xia Lijun
Department of Clinical Pharmacy, Lishui People's Hospital of Zhejiang Province, Lishui 323000
PR China

Abstract

Objective: To observe the short-term efficacy and safety of S-1 combined with cisplatin (DDP) chemotherapy for advanced gastric cancer (AGC). Materials and Methods: Sixty-six patients were diagnosed with AGC and were admitted to our department from February 2012 to January 2015 and retrospectively analyzed. Of these patients, 31 (experimental group) underwent S-1 combined with DDP chemotherapy and 35 received oxaliplatin combined with tegafur and calcium folinate chemotherapy regimen (control group). The chemotherapy regimen for the experimental group included S-1, 60 mg bid on d1–d14 and 60 mg/m 2 DDP by intravenous dripping on d1–d3, with 4 weeks in a cycle. The chemotherapy regimen for the control group consisted of 130 mg/m 2 oxaliplatin by intravenous dripping, d1; 600 mg/m 2 tegafur by intravenous dripping on d1–d5; and 120 mg/m 2 calcium folinate by intravenous dripping on d1–d5, with 3 weeks in a cycle. The efficacies and adverse effects of the two regimens were assessed after three cycles. Results: After three cycles, the objective response rates of the experimental and control groups were 41.94% and 42.86%, without significantly difference (P > 0.05), respectively. However, the incidence rate of adverse drug reactions in Grades 3–4 in the experimental group was significantly lower than that of control group (P < 0.05). Conclusion: The short-term efficacy of primary S-1 with DDP chemotherapy for AGC is relatively satisfactory with less adverse effects.



How to cite this article:
Weidong C, Lijun X. S-1 combined with cisplatin chemotherapy for advanced gastric cancer.J Can Res Ther 2016;12:54-56


How to cite this URL:
Weidong C, Lijun X. S-1 combined with cisplatin chemotherapy for advanced gastric cancer. J Can Res Ther [serial online] 2016 [cited 2022 Nov 27 ];12:54-56
Available from: https://www.cancerjournal.net/text.asp?2016/12/5/54/191631


Full Text



 Introduction



Gastric cancer is treated with a basic chemotherapy regimen involving cisplatin (DDP) and fluorouracil (5-FU).[1] As new 5-FU oral drugs, S-1 capsules are synthesized with tegafur (FT), a precursor for 5-FU, and by adding two biochemical modifiers, namely, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (OXO). The anti-tumor activity spectrum of S-1 capsules is similar to that of 5-FU; the capsules also exhibit a stronger potency against advanced gastric cancer (AGC) with relatively minimal adverse reactions than 5-FU does.[2] In this study, a total of 66 cases admitted to our hospital with AGC from February 2012 to January 2015 underwent primary S-1 (developed in China) chemotherapy combined with DDP. Moreover, the short-term efficacy of the proposed regimen was evaluated in this study.

 Materials and Methods



General information

A total of 66 cases with AGC in stage IIIB–IV (UICC TNM staging) after imaging (computed tomography [CT] and type-B ultrasonic check) and pathological diagnosis were included in this study. These cases comprised chemotherapy-naive patients with more than one measurable lesion but without surgical indications. The patients were characterized as follows: KPS score ≥70 points, normal organ functions, and expected survival ≥3 months. The patients also provided informed consent that they signed before they underwent chemotherapy. The two groups were comparable in terms of gender, age, pathological type, and clinical staging [Table 1].{Table 1}

Chemotherapy regimens

The regimen for the treated group was as follows: S-1 (Shandong New Times Pharmaceutical Co., Ltd.) and dose was rounded to the nearest integer and determined by body surface area. At a body surface area (m 2) of <1.25, the dose was 40 mg. At a body surface area of ≥1.25 to <–1.5, the dose was 50 mg. At a body surface area of ≥1.5, the dose was 60 mg. Two doses were orally administered per day: in the morning and evening from d1 to d21. DDP (60 mg/m 2) was intravenously administered on d1–d3, with 4 weeks in a cycle. The regimen for the control group was as follows: 125 mg/m 2 oxaliplatin was intravenously administered on d1, 600 mg/m 2 FT was intravenously given on d1–d5, and 120 mg/m 2 calcium folinate was intravenously administered on d1–d5, with 3 weeks in a cycle. Side reactions were closely observed during chemotherapy. The chemotherapy efficacies of the two groups after three cycles were assessed by the following parameters reviewed before and after each chemotherapy session: electrocardiogram, blood cells, blood coagulation, general biochemical examination, and tumor marker.

Evaluation criteria

The lesion size was observed through CT, and the efficacy was assessed using RECIST 1.1: complete response (CR), partial response (PR), stable disease (SD), and progressive disease. Objective response (OR) was examined as CR + PR and disease control rate was calculated as CR + PR + SD. Adverse effects were evaluated on the basis of the grading criteria provided by WHO (1998) and divided into four stages; stages 3–4 were serious.

Statistical analysis

Data were expressed as (x¯ ± s). T-test with counted data expressed in terms of rate was applied to conduct the between-group comparison. Chi-square test was also performed to verify the between-group comparison. Statistical analysis was carried out in Stata10.0 (http://www.stata.com; Stata Corporation, College Station, TX, USA).

 Results



Short-term efficacy

After three cycles, the OR rates of the experimental and control groups were 41.94% and 42.86%, respectively, with no statistical difference (P > 0.05) [Table 2].{Table 2}

Adverse effects

The adverse effects of the treated group were anorexia, leukopenia, nausea, vomiting, and weakness. These effects were generally in Grades 1–2 but rarely in Grades 3–4. The overall incidence rate of adverse drug reactions in Grades 3–4 accounted for 29.03%. The adverse effects on the control group were weakness, anorexia, nausea, vomiting, leukopenia, diarrhea, anemia, and oral mucositis. The overall incidence rate of adverse drug reactions in Grades 3–4 was 62.86%. The overall incidence rate of adverse drug reactions of the control group in Grades 3–4 was significantly higher than that of experimental group (P < 0.05).

 Discussions



In China, the incidence and mortality of gastric cancer are the highest among those recorded for various malignant tumors; these parameters have increased among young adults.[3],[4],[5] In middle- and late-stage gastric cancer, combined chemotherapy is highly recommended. In principle, highly efficient drugs with low toxicity and few side effects, different antitumor mechanisms, and nonoverlapping toxicity are recommended. In general, gastric cancer is relatively sensitive to chemotherapy. The effective rate of a combined chemotherapy is 30–50% according to publications.[6],[7] Considering these factors, we investigated the clinical efficacy of and S-1 combined with DDP chemotherapy for AGC.

S-1 was originally developed and publicly traded in Japan. In 2004, S-1 was recommended for a chemotherapy regimen combined with DDP for gastric cancer. In Japan, S-1 capsules have been considered the first-line drugs for advanced malignant tumors in gastrointestinal tracts with up to 44% efficacy against AGC.[8],[9] Chinese and Japanese races are very similar; therefore, the findings of S-1 in Japan have very high reference values for the Chinese population. In China, this drug has been approved for chemotherapy by the SFDA. S-1 is an oral anticancer of a 5-FU derivative and is composed of CDHP, OXO, and FT, and FT is a derivative of 5-FU. FT is a precursor of 5-FU characterized by good oral absorption and high bioavailability. Studies have shown [10] that FT can be converted to 5-FU in vivo and, thus, overcomes the disadvantage of orally administered 5-FU, which is incompletely absorbed. The chemotherapy index of FT is twice that of 5-FU, and the toxicity accounts for 1/4–1/7 of 5-FU; as a result, its anti-tumor activity is increased. CDHP can selectively inhibit dihydropyrimidine dehydrogenase in the liver, prevent the in vivo catabolism of 5-FU, and maintain a relatively high and s[table 5]-FU level in the blood plasma and tumor tissues within long periods. In this way, CDHO enhances the anti-tumor activity and overcomes the short half-life and fast metabolism of 5-FU. OXO is an important component of S-1 with a high distribution concentration in the gastrointestinal tissues after oral administration. OXO exhibits a selective antagonism against ORPT in the digestive tract; the toxicity and adverse reactions of 5-FU in the human gastrointestinal tract are reduced by up to 80% by inhibiting ORPT and preventing 5-FU from being phosphorylated into 5-FUMR. Therefore, S-1 is a new generation of safe and effective anticarcinogens, which can extend the efficacy of 5-FU in blood and tumor tissues, enhance antitumor effects, and reduce toxicity and side effects on the gastrointestinal tract.

The short-term efficacy of primary S-1 chemotherapy with DDP for AGC is relatively satisfactory, with less adverse effects. Consistent with the clinical trial results of SPIR-ITS III in Japan,[11] S-1 (developed in China) combined with DDP chemotherapy regimen for AGC exhibited satisfactory efficacy and safety. The clinical benefit rate of S-1 is higher than that of the Folfox4 regimen. As a result, the quality of life of patients is significantly improved and the adverse effects of the proposed regimen are reduced. This regimen should also be promoted in clinical practice because of its short intravenous drip, convenient oral medication, and enhanced patient compliance. Furthermore, this regimen is particularly suitable for the elderly or physically weak patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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