A Retrospective Analysis of the Relation Between Durations of Adjuvant Chemotherapy with Its Effects on Overall Survival and Relapse Free Survival in Stage Ii or III Gastric Cancer

Purpose The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study. Patients and Methods Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety. Results The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic. Conclusion On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2003.06.103 ◽

2003 ◽

Vol 21 (12) ◽

pp. 2282-2287 ◽

Cited By ~ 111

Author(s):

Atsushi Nashimoto ◽

Toshifusa Nakajima ◽

Hiroshi Furukawa ◽

Masatsugu Kitamura ◽

Taira Kinoshita ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Survival Benefit ◽

Curative Resection ◽

Cancer Recurrence ◽

Phase Iii ◽

Relapse Free Survival ◽

Free Survival ◽

Significant Difference

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 randomly 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.

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Neoadjuvant Chemotherapy with Fluorouracil plus Leucovorin, Oxaliplatin, and Docetaxel (FLOT) for Gastric Cancer Patients in China

10.1101/2020.05.22.20110668 ◽

2020 ◽

Cited By ~ 1

Author(s):

Birendra Kumar Sah ◽

Xu Wei ◽

Zhang Benyan ◽

Zhang Huan ◽

Yuan Fei ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Chemotherapy ◽

Tumor Regression ◽

Chinese Patients ◽

Relapse Free Survival ◽

Free Survival ◽

Grade 3 ◽

Gastric Cancer Patients

AbstractPurposeNeoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries, so we conducted a prospective study on the safety and feasibility of this regimen in Chinese patients.MethodsPatients with adenocarcinoma of the stomach or esophagogastric junction received 4 cycles of neoadjuvant chemotherapy (NAC) and 4 cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities and pathological tumor regression were analyzed. The two-year overall survival (OS) and relapse-free survival are presented.ResultsAltogether, 10 patients were enrolled, and all patients completed 4 cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and 3 patients had complete or subtotal pathological tumor regression. Nine patients completed 4 cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, 8 patients achieved the overall survival endpoint, and 7 patients had relapse-free survival for this period. Two patients died of disease progression.ConclusionsOur study demonstrates that neoadjuvant chemotherapy with FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort.

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Feasibility and Safety of Perioperative Chemotherapy With Fluorouracil Plus Leucovorin, Oxaliplatin, and Docetaxel for Locally Advanced Gastric Cancer Patients in China

Frontiers in Oncology ◽

10.3389/fonc.2020.567529 ◽

2021 ◽

Vol 10 ◽

Author(s):

Birendra Kumar Sah ◽

Wei Xu ◽

Benyan Zhang ◽

Huan Zhang ◽

Fei Yuan ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Chemotherapy ◽

Tumor Regression ◽

Chinese Patients ◽

Relapse Free Survival ◽

Free Survival ◽

Grade 3 ◽

Gastric Cancer Patients

BackgroundNeoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of the FLOT regimen in Chinese patients.MethodsPatients with adenocarcinoma of the stomach or esophagogastric junction received four cycles of neoadjuvant chemotherapy (NAC) and four cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities, and pathological tumor regression were analyzed. The 2-year overall survival (OS) and relapse-free survival are presented.ResultsAltogether, 10 patients were enrolled, and all patients completed four cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and three patients had complete or subtotal pathological tumor regression. Nine patients completed four cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, eight patients achieved the overall survival endpoint, and seven patients had relapse-free survival for this period. Two patients died of disease progression.ConclusionsOur study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort. The trial is registered with ClinicalTrials.gov (number NCT03646591).

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Randomized Clinical Trial of Adjuvant Mitomycin Plus Tegafur in Patients With Resected Stage III Gastric Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.12.3810 ◽

1999 ◽

Vol 17 (12) ◽

pp. 3810-3815 ◽

Cited By ~ 82

Author(s):

Lluís Cirera ◽

Anna Balil ◽

Eduard Batiste-Alentorn ◽

Ignasi Tusquets ◽

Teresa Cardona ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trial ◽

Overall Survival ◽

Survival Rate ◽

Adjuvant Chemotherapy ◽

Disease Free Survival ◽

Stage Iii ◽

Free Survival ◽

Resected Stage ◽

Disease Free

PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m2 intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P = .04 for survival and P = .01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer.

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Phase II feasibility study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0604).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.108 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 108-108 ◽

Cited By ~ 1

Author(s):

Jin Matsuyama ◽

Shigeyuki Tamura ◽

Kazumasa Fujitani ◽

Yutaka Kimura ◽

Takeshi Tsuji ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Phase Ii ◽

Stage Iii ◽

Free Survival ◽

D2 Dissection ◽

Grade 3 ◽

Gastric Cancer Patients

108 Background: An adjuvant chemotherapy with S-1 has become the standard treatment for patients (pts) with stage II/III gastric cancer (GC) who have undergone gastrectomy with D2 dissection in Japan, but it is assumed that the survival benefit for stage III pts who received S-1 is modest. S-1 plus docetaxel has shown that the response rate and median overall survival (OS) were 56% and 14.3 months in pts with advanced GC. The aims of this phase II study were to evaluate the feasibility and safety of adjuvant S-1 plus docetaxel in pts with stage III GC with D2 surgery. Methods: Pts with pathological stage III GC who underwent gastrectomy with D2 dissection received oral S-1 (80 mg/m2/day) administration for 2 consecutive weeks and intravenous docetaxel (40 mg/m2) on day 1, repeated every 3 weeks (1 cycle). The treatment was started within 45 days after surgery, and repeated for 4 cycles, followed by S-1 administration until 1 year after surgery. The primary endpoint was feasibility of the 4 cycles administration of S-1 plus docetaxel; secondary endpoints were safety, progression-free survival (PFS), OS, and feasibility of S-1 administration until 1 year after surgery. Results: We enrolled 53 pts, 42 males and 11 females with a median age of 65 years (range, 43-78), between May 2007 and August 2008. Pathological stages included IIIA in 36 pts and IIIB in 17 pts. The feasibility of planned 4 cycles of treatment was 77.4% (95% CI 63.8-87.7%, p < 0.001) with 41 pts out of 53 pts. Grade 4 neutropenia was observed in 28% of pts with grade 3 febrile neutropenia in 9%. Non-hematological toxicities of grade 3 or more involved fatigue in 6%, anorexia in 9%, and nausea in 6%. No treatment-related deaths occurred. Reasons for discontinuation were recurrent cancer in 1 pt, adverse events in 10, and miscellaneous in 1, respectively. 3 year overall survival was 78.8% (95% CI 68.4-90.7) and 3 year disease free survival was 50.3% (95% CI 34.4-73.3). Conclusions: Adjuvant S-1 plus docetaxel therapy is feasible and has only moderate toxicity in stage III gastric cancer pts. We believe that this regimen will be a candidate for future phase III trials seeking the optimal adjuvant chemotherapy for stage III gastric cancer patients.

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Cochrane systematic review and meta-analysis of adjuvant chemotherapy for stage II colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.3548 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 3548-3548

Author(s):

Brandon Matthew Meyers ◽

Humaid Obaid Al-Shamsi ◽

Alvaro Tell Figueredo

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Meta Analysis ◽

Disease Free Survival ◽

Stage Ii ◽

Cochrane Systematic Review ◽

Free Survival ◽

Stage Ii Colon Cancer ◽

Disease Free

3548 Background: Colon cancer is potentially curable by surgery in the early stages of the disease. Adjuvant chemotherapy improves disease-free and overall survival in patients with stage III disease, but the magnitude of benefit in stage II colon cancer is less clear. A previous Cochrane systematic review and meta-analysis (SR/MA) found improved disease-free, but not overall survival (Figueredo et al., 2008). An updated SR/MA was performed to determine the effects of adjuvant chemotherapy on disease-free and overall survival in patients with stage II colon cancer. Methods: Relevant databases (MEDLINE, EMBASE, and Cochrane) were independently searched by all authors, using the same search strategy employed in the original study (1/1988 to 9/2012). Randomized trials containing data on stage II colon cancer patients undergoing adjuvant 5-fluorouracil (5FU) chemotherapy versus observation were included. Pooled results were expressed as hazard ratios (HR) whenever possible, or risk ratios (RR), with 95% confidence intervals (95%CI) using a random effects model. Results: Seven studies were identified, and included in the final SR/MA. Six of the 7 studies were included in the disease-free survival analysis (n=4587). Adjuvant 5FU was associated with better disease-free survival (RR 0.84 (95%CI 0.75-0.94)). All 7 studies (n=5353) were included in the overall survival analysis showing an improvement with adjuvant 5FU (HR 0.87 (95%CI 0.78-0.97)). There was no evidence of heterogeneity across the studies (I2 = 0% for all analyses). Conclusions: In stage II colon cancer, adjuvant 5FU chemotherapy statistically improves both disease-free and overall survival. Our SR/MA demonstrates, for the first time, an overall survival advantage with adjuvant chemotherapy in stage II colon cancer.

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Subset of patients with unfavorable T1N2-3M0 gastric cancer for whom surgery alone is the standard treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.105 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 105-105

Author(s):

Yukio Maezawa ◽

Tsutomu Sato ◽

Toru Aoyama ◽

Kazuki Kano ◽

Kenki Segami ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Standard Treatment ◽

Stage Ii ◽

Rank Test ◽

Cancer Center ◽

Tumor Diameter ◽

Significant Difference ◽

Macroscopic Tumor

105 Background: ACTS-GC trial demonstrated that S-1 is effective as adjuvant chemotherapy for Japanese patients who have undergone curative D2 gastrectomy for gastric cancer and were diagnosed with pathological stage II disease. However, stages T1N2M0 and T1N3M0, which are classified as part of Stage II, were excluded from the ACTS-GC trial. The aim of the present study was to identify the unfavorable subset of patients with T1N2M0 and T1N3M0 gastric cancer for whom surgery alone is the standard treatment. Methods: The present study examined 59 patients who were diagnosed with T1N2M0 or T1N3M0 gastric cancer at Kanagawa Cancer Center and Yokohama City University Hospital between January 2000 and June 2010. Univariate and multivariate analyses were performed to identify risk factors for overall survival using a Cox proportional hazards model. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter. A macroscopic tumor diameter greater than 30mm was regarded as a critical point of classification considering the survival. Mulitivariate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 60.0% in patients with a macroscopic tumor diameter < 30mm, and 84.6% in those with a macroscopic tumor diameter > 30mm (P = 0.027). Conclusions: Among T1N2M0 and T1N3M0 gastric cancer patients for whom surgery alone is the standard treatment, having a small T1N2-3 tumor of less than 30 mm in diameter was the sole risk factor for gastric cancer survival. These tumors might be another target for adjuvant chemotherapy.

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Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.11.2757 ◽

1995 ◽

Vol 13 (11) ◽

pp. 2757-2763 ◽

Cited By ~ 76

Author(s):

M Lise ◽

D Nitti ◽

A Marchet ◽

T Sahmoud ◽

M Buyse ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trial ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Adjuvant Treatment ◽

Stage Ii ◽

Phase Iii ◽

Stage Iii ◽

Time To Progression ◽

Disease Free

PURPOSE In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.

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