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S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial.

ABSTRACT: PURPOSE:We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. Materials and Methods:Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2 /day on days 1-14 plus docetaxel 35 mg/m2 on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2 /day on days 1-14 plus cisplatin 60 mg/m2 on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS:Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION:Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

SUBMITTER: Lee CK

PROVIDER: S-EPMC6333977 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial.

Lee Choong-Kun CK Jung Minkyu M Kim Hyo Song HS Jung Inkyung I Shin Dong Bok DB Kang Seok Yun SY Zang Dae Young DY Kim Ki Hyang KH Lee Moon Hee MH Kim Bong-Seog BS Lee Kyung Hee KH Cheong Jae-Ho JH Hyung Woo Jin WJ Noh Sung Hoon SH Chung Hyun Cheol HC Rha Sun Young SY

Cancer research and treatment 20180205 1

<h4>Purpose</h4>We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients.<h4>Materials and methods</h4>Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2 /day on days 1-14 plus docetaxel 35 mg/m2 on days 1 and 8) every 3 weeks ...[more]

PMID: 29397659

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Project description:BackgroundMesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear.Subjects, materials, and methodsMesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition.ResultsHigh mesothelin expression was observed in 49.7% of patients and significantly associated with high pathologic T (p = .021) and peritoneal recurrence (p = .018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p = .001), OS (p = .001), and peritoneal recurrence (p = .002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p = .013) and diffuse/mixed type gastric cancer (p = .010).ConclusionHigh mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer.Implications for practiceThis study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.

Project description:ImportanceThe current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy.ObjectiveTo construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer.Design, setting, and participantsIn this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study's inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016.Main outcomes and measuresConcordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival.ResultsOf the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival and disease-free survival, with P < .05. The survival prediction model demonstrated good calibration and discrimination, with relatively high bootstrap-corrected concordance indexes in the training and validation cohorts. In the validation cohort, the concordance index for overall survival was 0.693 (95% CI, 0.671-0.715) and for disease-free survival was 0.704 (95% CI, 0.681-0.728). Two nomograms and a calculating tool were built on the basis of specific input variables to estimate an individual's net survival gain attributable to adjuvant chemotherapy.Conclusions and relevanceThe survival prediction model can be used to make individualized predictions of the expected survival benefit from the addition of adjuvant chemotherapy for patients with stage II or stage III gastric cancer.

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Dataset Information

S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial.

Publications

S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial.

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