Neoadjuvant therapy of high-risk gastric cancer: a phase II trial of preoperative FAMTX and postoperative intraperitoneal fluorouracil-cisplatin plus intravenous fluorouracil. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1. Chemotherapy for operable gastric cancer: results of the Dutch randomised FAMTX trial. The Dutch Gastric Cancer Group (DGCG). Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced gastric cancer Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer
PURPOSE AND METHODS We identified patients with gastric cancer at high risk for recurrence before therapy using endoscopic ultrasonography ( EUS ) .  Neoadjuvant therapy using the fluorouracil , doxorubicin , and metrotrexate ( FAMTX ) regimen was given for three courses before planned laparotomy with the intention to perform curative resection . Postoperatively , intraperitoneal ( IP ) cisplatin and fluorouracil ( FU ) and intravenous ( i.v . ) FU were administered to patients undergoing resection . RESULTS Fifty-six assessable patients were treated . Preoperative FAMTX therapy was tolerable , with the major toxicity being neutropenic fever . One treatment-related death was seen . Eighty-nine percent of patients underwent surgical exploration and 61 % had potentially curative resections . There were two postoperative deaths . Comparison of pathologic tumor ( pT ) stage with EUS-predicted tumor stage showed apparent downstaging in 51 % of patients . Postoperative IP chemotherapy was delivered to 75 % of eligible patients . Toxicity was acceptable . There was no increase in operative morbidity or mortality compared with concurrent non study patients undergoing a similar operative procedure and not receiving preoperative therapy . With a median follow-up time of 29 months , the median survival duration was 15.3 months . For patients who underwent potentially curative resections , the median survival duration was 31 months . Peritoneal failure was seen in 16 % of patients . CONCLUSION Chemotherapy with the FAMTX regimen is tolerable in patients with locally advanced gastric cancer , without an increase in operative morbidity or mortality . IP therapy can be successfully delivered to most resected patients . The intraabdominal failure pattern appears to be decreased compared with expected . This approach is an appropriate investigational arm to pursue in future studies Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies PURPOSE To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients ( excluding patients who were T1N0 ) , we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated . PATIENTS AND METHODS From January 1993 to December 1994 , 252 patients were enrolled into the study and allocated r and omly to adjuvant chemotherapy or surgery alone . The chemotherapy comprised intravenous mitomycin 1.33 mg/m2 , fluorouracil ( FU ) 166.7 mg/m2 , and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery , and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2 . The primary end point was relapse-free survival . Overall survival and the site of recurrence were secondary end points . RESULTS Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection . There were no treatment-related deaths and few serious adverse events . There was no significant difference in relapse-free and overall survival between the arms ( 5-year relapse-free survival 88.8 % chemotherapy v 83.7 % surgery alone ; P = .14 and 5-year survival 91.2 % chemotherapy v 86.1 % surgery alone ; P = .13 , respectively ) . Nine patients ( 7.1 % ) in the chemotherapy arm and 17 patients ( 13.8 % ) in the surgery-alone arm had cancer recurrence . CONCLUSION There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection , and there was no statistical difference between the two arms relating to the types of cancer recurrence . We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice The aim of this trial was to investigate whether pre-operative chemotherapy leads to a 15 % higher curative resectability rate in patients with operable gastric cancer . In this r and omised trial , patients were allocated to receive either four courses of chemotherapy using 5-fluorouracil , doxorubicin and methotrexate ( FAMTX ) prior to surgery or to undergo surgery only .  Patients younger than 75 years of age with a good physical and mental condition and a histologically proven adenocarcinoma of the stomach without clinical or radiographic ( computed tomography scan ) evidence of distant metastases were eligible for this trial . Early gastric cancer or cardia carcinoma were excluded . The response to chemotherapy was evaluated after two and four courses . In case of progressive disease ( PD ) after two courses , patients were operated upon as soon as possible . Otherwise complete response ( CR ) partial response ( PR ) or stable disease ( SD ) , two more courses were scheduled . The st and ard surgical procedure was a limited lymphadenectomy ( D1 ) with staging biopsy of the para-aortic lymph nodes . Between September 1993 and February 1996 , 56 eligible and evaluable patients were entered : 27 were r and omised to receive FAMTX before surgery and 29 to undergo surgery only . In the FAMTX + surgery treatment group , 15/27 ( 56 % ) had curative resections versus 18/29 ( 62 % ) in the surgery only arm . There was no difference in the frequency of TNM stages I + II in both treatment arms : 15/27 versus 15/29 . Due to PD and /or toxicity , 12 patients ( 44 % ) could not complete the planned four courses of FAMTX . Response evaluation after chemotherapy was possible in 25 patients : 2 CR , 6 PR , 8 SD and 9 PD . The difference in curative resectability rate was 6.5 % ( 95 % confidence interval -32 to + 19 % ) in favour of surgery only . Downstaging for stages I + II did not occur . PD was more often the reason for not completing the planned four courses than toxicity . More active regimens than FAMTX are required for future r and omised trials We examined the role of neoadjuvant therapy in downstaging locally advanced gastric cancer . Preoperative staging was performed with a combination of CT scans , endoscopic ultrasonography and /or laparoscopy , and laparoscopic ultrasonography . Patients with T ⋝3 tumors and /or node-positive disease by preoperative clinical staging were eligible for entry .  Neoadjuvant therapy consisted of two cycles of CPT-11 ( 75 mg/m2 ) with cisplatin ( 25 mg/m2 ) weekly four times every 6 weeks . This was followed by resection with D2 lymph node dissection and two cycles of intraperitoneal chemotherapy with floxuridine and cisplatin .  Twenty-two patients were entered into the study ( 4 with T3N0 disease and 18 with T3N1 disease ) . Induction chemotherapy was well tolerated with major toxicities being neutropenia and diarrhea . A median of 78%/75 % of the planned dosage of CPT-11/cisplatin was delivered . Two patients withdrew consent during the first cycle and were lost to follow-up . One patient progressed to stage IV disease during induction chemotherapy and did not undergo surgery . Nineteen patients underwent surgery . One patient had undetected stage IV disease ( liver ) and underwent a palliative R2 resection . Of the 18 remaining patients , 17 had curative R0 resections and one had a palliative R1 resection . A median of 21 lymph nodes ( range 1 to 121 ) were examined histologically . There was one postoperative death . Surgical morbidity did not appear to increase after the neoadjuvant regimen . The median postoperative length of hospital stay was 9 days ( range 3 to 75 days ) . Postoperative pathologic staging yielded 16 % T3 lesions compared to 85 % before treatment based on clinical staging ; postoperative American Joint Committee on Cancer staging yielded 37 % stage IIIA disease compared to 70 % stage IIIA before treatment . With a median follow-up of 15 months , median survival has not yet been reached . We conclude that CPT-11-based neoadjuvant therapy downstages locally advanced gastric cancer . Further follow-up is necessary to determine the ultimate impact of this combination therapy on recurrence and survival Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy . This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma
Background : National Comprehensive Cancer Network ( NCCN ) guidelines recommend surgery , chemotherapy , and radiation therapy for gastric cancer patients .
Neoadjuvant treatments as the administration of therapeutic agents before a main treatment gained in more and more attention .
However , the role of neoadjuvant treatments is still controversial .
The main aim of this systematic review and network meta- analysis is to assess the relative efficacy of different neoadjuvant treatment regimens for gastric cancer using network meta- analysis method .