surgery is the main treatment strategy for gastric cancer ; only r0 resection anticipates a potential cure .
the prognosis of initially unresectable gastric cancer is poor ; approximately 50% of patients have recurrent disease after a curative resection .
this suggests that micrometastases are already present , in many cases , at the time of surgery1 ) .
neoadjuvant chemotherapy has been attempted for the treatment of gastric cancers in patients with advanced t and n stage disease for the purpose of downstaging , improving resectability and survival2 ) .
these regimens have demonstrated a response rate ( rr ) of 3 4~69% and a resectability of 36~60% , with a median survival of 16~28 months for initially unresectable or stage iii - iv cases .
however , in 19~33% of patients , the associated adverse effects of up to grade 3 - 4 have impeded the use of these agents3 - 6 ) .
therefore , the selection of patients with a good performance status is the first consideration for effective neoadjuvant chemotherapy .
s-1 is a fourth - generation oral fluoropyrimidine based on the combination of tegafur with two biochemical modulators , 5-chloro-2,4-dihydroxypyridine ( cdhp ) and potassium oxonate ( oxo ) .
s-1 mimics the protracted continuous infusion of 5-fluorouracil ( 5-fu ) with enhanced efficacy and safety7 ) .
one earlier and two more current , phase ii trials with monotherapy for advanced gastric cancer , in japan , achieved a remarkable rr of 45% and 54% respectively .
these results are consistent with the commonly used combination regimens containing cisplatin or anthracyclines8 , 9 ) .
s-1 is also known to have less toxicity than other active agents in the treatment of gastric cancer .
nevertheless , there are only a few reports evaluating its efficacy for neoadjuvant treatment . in retrospective analyses ,
s-1 in combination with cisplatin achieved a rr of 44% and 79% and a downstaging rate of 47% and 85% , respectively10 , 11 ) .
furthermore , s-1 monotherapy as neoadjuvant treatment has recently been reported to induce a pathologically complete response ( cr)12 , 13 ) and curative resection .
based on these data , we report herein s-1 monotherapy as neoadjuvant treatment in a patient with locally advanced gastric cancer and poor performance status who achieved a curative resection .
a 68-year - old man with epigastric pain , anorexia and general weakness for 6 months was admitted to our hospital .
there was neither history of pre - existing chronic disease nor a family history of gastric cancer .
his performance status was 2 according to the criteria of the eastern cooperative oncology group ( ecog ) .
endoscopic examination demonstrated a diffuse - infiltrative lesion along the great curvature of the upper body of the stomach ; the biopsy confirmed a moderately differentiated adenocarcinoma ( figure 1a , 1b ) .
abdominal - pelvic computed tomography ( ct ) showed a gastric cancer with massive lymph node enlargement in the perigastric area , upper retroperitoneum close to the celiac axis and the splenic hilum with no evidence of distant or peritoneal metastases ( figure 1c , 1d , 1e ) .
the clinical stage of the patient was ct3n2h0p0m0 according to the staging system of the japanese gastric cancer association ( jgca ) .
. however , significant weight loss , advanced age and a relatively poor general condition prevented full - dose administration of a multi - drug systemic chemotherapy regimen .
alternately , we planned s-1 monotherapy at a dose of 35 mg / m twice a day for 4 consecutive weeks followed by a 2-week resting period .
follow - up endoscopy after 4 cycles showed a decrease in the extent of infiltrative lesions of the stomach ( figure 2a ) .
the ct scan demonstrated the disappearance of lymph node enlargement around the perigastric area , celiac axis and also a decrease in the size of the splenic hilar lymph nodes along with a reduction in the stomach mass ( figure 2b , 2c , 2d ) . according to the recist criteria , a pr with a 72% decrease of the target lesions ( sum of target lesion
, 90 mm to 26 mm ) was achieved . during the 4 cycles of treatment
the patient had grade 1 fatigue and nausea and grade 2 skin rashes without any grade 3 - 4 toxicity .
the performance status improved to ecog 1 after the administration of s-1 and the patient gained 7 kg of body weight .
the diagnostic laparoscopy showed a serosa - involving lesion on the upper body of the stomach extending from the anterior to the posterior wall with severe adhesions and surrounding tissues .
macroscopically , the excised specimen showed a diffuse infiltrative lesion with serosal surface exposure ( se ) measuring 180130 mm .
an adequate resection margin was obtained on both ends and there was no microscopic involvement at the margins identified . according to becker 's criteria , more than 50% of the tumor bed was composed of tumor cells ; therefore , the pathological response was defined as minor14 ) .
the final pathological stage was pt3n2m0 ( h0p0 ) , stage iiib , according to both the jgca and the american joint committee on cancer ( ajcc ) systems .
after an additional 3 cycles of s-1 monotherapy were administered as adjuvant chemotherapy , the patient is without any evidence of recurrence after 6 months of follow - up .
. early initiation of systemic therapy may result in disease downstaging , eliminate micrometastases and enable a curative resection .
furthermore , neoadjuvant chemotherapy provides prognostic information due to the in vivo chemosensitivity testing . however , there are also potential risks involved . by delaying definitive local therapy ,
in addition , considerable tumor shrinkage is required in a short period for the chemotherapeutic regimen to obtain effective downstaging with the neoadjuvant treatment .
therefore , neoadjuvant therapy may not be feasible in some circumstances such as in patients with an unfavorable performance status or advance age . in the clinical trials using cisplatin or anthracycline - based regimens
, although downstaging was attained , only 20~54% of the patients completed the planned treatment .
as many as one - third of the patients experienced grade 3 - 4 adverse events3 - 6 ) .
therefore , novel chemotherapeutic agents such as taxanes , irinotecan and oral fluoropyrimidines might be candidates for future neoadjuvant trials with effects on tumor shrinkage comparable to and more favorable toxicity profiles than traditional agents . among the above cited agents
, s-1 might be a useful treatment option because of the results of several phase ii trials on advanced gastric cancer .
two japanese retrospective analyses of s-1 , in combination with cisplatin as neoadjuvant treatment in stage iii - iv disease , achieved a rr of 44% and 79% and a downstaging rate of 47% and 85% , respectively . however , these high responses are mainly due to a high pr not a pathological cr possibly implicating a survival benefit10 , 11 ) .
recently , preoperative administration of s-1 alone has been shown to induce favorable responses in patients in poor clinical condition .
the total disappearance of peritoneal dissemination was observed with s-1 and cisplatin , and there was a pathological cr in a 78-year old patient who was treated with s-1 alone12 ) .
our patient was not a candidate for full - dose multi - drug systemic chemotherapy due to his poor health status .
although downstaging was not observed in our case , probably due to a very large initial tumor burden , there was marked resolution of the massive lymphadenopathy around the celiac axis .
this is consistent with other phase ii studies on s-1 monotherapy that reported a higher efficacy for the abdominal lymph nodes ( 75% ) compared to the primary gastric mass ( 28% ) or visceral organs ( 30%)9 ) .
another aspect of neoadjuvant chemotherapy to consider is safety , which in turn is associated with treatment compliance . in this respect
neutropenia and anemia were the main adverse events reported in asian patients9 , 15 ) and the neoadjuvant combination with cisplatin showed only 7% of cases with grade 3 - 4 adverse events10 , 11 ) .
moreover , the patient reported a sense of well being , had an improved appetite and gained weight . therefore , s-1 monotherapy was safe and effective treatment for this patient and might be considered in the future as neoadjuvant treatment for gastric cancer . in conclusion , the results of this case study suggest that s-1 might be a safe and effective treatment option for neoadjuvant chemotherapy in locally advanced gastric cancer , especially when accompanied byperigastric lymphadenopathy and a poor general health status in patients of advanced age .
the role of s-1 in the neoadjuvant setting for the treatment of gastric cancer remains to be established by clinical trials .
 s-1 , a novel oral fluoropyrimidine , is an effective therapeutic agent for gastric cancer . 
 herein , we report a case with locally advanced gastric cancer that achieved a curative resection after s-1 monotherapy as neoadjuvant treatment . 
 a 68-year - old man was diagnosed with gastric cancer and massive lymphadenopathy involving the perigastric , celiac axis and splenic hilum . 
 his clinical stage was ct3n2h0p0m0 . 
 considering his relatively poor performance ( ecog 2 , severe weight loss ) and advanced age , we started the patient on s-1 monotherapy at a dose of 35 mg / m2 bid for 4 consecutive weeks followed by a 2-week rest . 
 follow - up study after 4 treatment cycles revealed disappearance of the lymphadenopathy of the perigastric and celiac axis with diminished extension of the stomach mass . 
 the patient had a partial response ( pr ) with a 72% tumor reduction , according to the response evaluation criteria in solid tumors ( recist ) . 
 his performance status was improved to an ecog 1 and he gained 7 kg . 
 a curative ( r0 ) resection was achieved with a radical total gastrectomy and d2 dissection . 
 the pathological stage was pt3n2m0 , stage iiib . in conclusion , 
 s-1 neoadjuvant chemotherapy aided in the treatment of gastric cancer in this patient . 
INTRODUCTION
CASE REPORT
DISCUSSION