S-1 And Oxaliplatin Research Articles

Pathologic Response of Phase III Study: Perioperative Camrelizumab Plus Rivoceranib and Chemotherapy Versus Chemotherapy for Locally Advanced Gastric Cancer (DRAGON IV/CAP 05).

This multicenter, randomized phase III trial evaluated the efficacy and safety of perioperative camrelizumab (an anti-PD-1 antibody) plus low-dose rivoceranib (a VEGFR-2 inhibitor) and S-1 and oxaliplatin (SOX) (SOXRC), high-dose rivoceranib plus SOX (SOXR), and SOX alone (SOX) for locally advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Patients with T3-4aN + M0 G/GEJ adenocarcinoma were randomly assigned (1:1:1) to receive perioperative treatment with SOXRC, SOXR, or SOX. The primary end points were pathologic complete response (pCR) and event-free survival. The Independent Data Monitoring Committee recommended stopping enrollment in the SOXR group on the basis of the safety data of the first 103 randomly assigned patients in the three groups. The patients were then randomly assigned 1:1 to the SOXRC or SOX groups. This report presents the pCR results obtained per protocol for the first 360 randomly assigned patients who had the opportunity for surgery in the SOXRC and SOX groups. In the SOXRC and SOX groups, of the 180 patients in each group, 99% and 98% of patients received neoadjuvant therapy, 91% and 94% completed planned neoadjuvant therapy, and 86% and 87% underwent surgery, respectively. The pCR was significantly higher in the SOXRC group at 18.3% (95% CI, 13.0 to 24.8) compared with 5.0% (95% CI, 2.3 to 9.3) in the SOX group (difference of 13.7%; 95% CI, 7.2 to 20.1; odds ratio of 4.5 [95% CI, 2.1 to 9.9]). The one-sided P value was <.0001, crossing the prespecified statistical significance threshold of P = .005. Surgical complications and grade ≥3 neoadjuvant treatment-related adverse events were 27% versus 33% and 34% versus 17% for SOXRC and SOX, respectively. The SOXRC regimen significantly improved pCR compared with SOX alone in patients with G/GEJ adenocarcinoma with a tolerable safety profile.

Novel computed tomography-based nomograms for the pretherapeutic prediction of response to neoadjuvant chemotherapy with S-1 and oxaliplatin with or without the addition of docetaxel in patients with advanced gastric cancer.

Selecting the appropriate preoperative neoadjuvant chemotherapy (NACT) regimen for patients with advanced gastric cancer (GC) is critical to effective treatment. The aim of this study was to develop nomograms based on pretherapeutic computed tomography (CT) features to predict response to NACT with S-1 and oxaliplatin (SOX) or that with docetaxel and SOX (DOS) in patients with advanced GC. This study enrolled 311 consecutive patients with confirmed advanced GC undergoing contrast-enhanced CT before and after the three cycles of NACT with DOS (n=152) or SOX (n=159), who were randomized into a training cohort (TC) (NACT with DOS: n=111; NACT with SOX: n=120) and validation cohort (VC) (NACT with DOS: n=41; NACT with SOX: n=39). The objective response rate (ORR) was used to evaluate the response to NACT. In the TC, ORR was compared between the DOS and SOX regimens, and independent predictors including CT features and tumor differentiation were determined by univariate and binary logistic regression analyses. Individual nomograms were constructed for the SOX and DOS regimens in the TC, and the predictive accuracy was validated in the VC. After NACT, the percentage of ORR was higher in patients receiving DOS than in those receiving SOX in TC (P value <0.05). The independent predictors after DOS and SOX were pretherapeutic cT stage [odds ratio (OR) =7.364; OR =8.848], cN stage (OR =1.027; OR =1.345), degree of differentiation (OR =7.127; OR =7.835), and gross tumor volume (OR =8.960; OR =8.161) (all P values <0.05). The concordance indexes of the individual nomograms developed using these predictors were 0.940 and 0.932 after DOS or SOX in the TC, respectively, which was validated by calibration plots with a slope close to 45° in the TC and VC. Despite there being a superior response to DOS compared with SOX, nomograms for predicting response to both NACT regimens were similar, with each demonstrating good predictive performance.

Perioperative PD-1 antibody tislelizumab plus chemotherapy for locally advanced gastro-oesophageal junction cancer: A prospective, nonrandomized, open-label, phase II trial.

4083 Background: The combination of PD-1 antibody and chemotherapy was shown to be effective in advanced gastric cancer, but has not yet been comprehensively investigated in locally advanced patients, especially in the context of adenocarcinoma of gastro-oesophageal junction (GEJ). In this study, we conducted a prospective, nonrandomized, open-label phase II trial to evaluate the effectiveness of adding PD-1 antibody to perioperative chemotherapy in patients with locally advanced resectable GEJ cancer. Methods: In this nonrandomized, open-label, phase II study, patients with resectable GEJ adenocarcinoma clinically staged as cT3-4aNanyM0 or cT1-2N+M0 were allocated three preoperative and five postoperative 3-week cycles of PD-1 antibody tislelizumab plus SOX (S-1 and oxaliplatin) regimen. The primary endpoint was major pathological response (MPR) rate. The secondary endpoints were pathological complete response (pCR), pathological complete /moderate regression rate (TRG 0/1), R0 resection rate, recurrence-free survival, event-free survival, overall survival, treatment safety and quality of life. The trial is registered at Chinese Clinical Trial Registry, identifier: ChiCTR2200058732. Results: Between Oct 2022 and June 2023, 32 patients were enrolled and assessed using intention-to-treat analysis. The median age was 60 years (range: 28-74 years), and 53.1% (17/32) patients were Siewert III type. All patients received at least one cycle of assigned preoperative treatment, and 96.9% (31/32) patients completed three cycles of assigned preoperative tislelizumab and SOX. R0 resection rate was 96.9% (31/32). The MPR rate was 37.5% (12/32, 95% CI: 21.1%-56.3%) and the pCR rate was 28.1% (9/32, 95% CI: 13.7%-46.7%). The surgical morbidity was 12.5% (4/32), and no 30-day mortality was observed. In the preoperative and postoperative treatment period, treatment-related grade 3-4 adverse events was 9.4% (3/32). At the date of 6th Feb 2024, three (9.4%) patients occurred recurrence. Conclusions: This is the first prospective study that focus on the perioperative immunotherapy in patients with resectable GEJ adenocarcinoma. Perioperative PD-1 antibody tislelizumab plus chemotherapy demonstrated a significantly improved pathological regression and might be a promising option for patients with locally advanced resectable GEJ adenocarcinoma. Clinical trial information: ChiCTR2200058732.

Multicenter randomized phase II study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases (YCOG1001).

The high recurrence rate of colorectal cancer liver metastasis (CRCLM) after surgery remains a crucial problem. However, adjuvant chemotherapy after hepatectomy for CRCLM has not yet been established. This study evaluated the efficacy of adjuvant therapy with S-1 and oxaliplatin (SOX). In a multicenter, randomized, phase II study, patients undergoing curative resection of CRCLM were randomly enrolled in a 1:1 ratio to either the low- or high-dose group. S-1 and oxaliplatin were administered from days 1 to 14 of a 3-week cycle as a 2-h infusion every 3weeks. The dose of S-1 was fixed at 80mg/m2. The doses in the low- and high-dose oxaliplatin groups were 100mg/m2 (low-dose group) and 130mg/m2 (high-dose group), respectively. This treatment was repeated eight times. The primary endpoint was the rate of discontinuation owing to toxicity. The secondary endpoints were the relapse-free survival (RFS) and frequency of adverse events (AEs). Between August 2010 and March 2015, 44 patients (low-dose group: 31 patients and high-dose group: 13 patients) were enrolled in the study. Of these, one patient was excluded from the efficacy analysis. In the high-dose group, five of nine patients were unable to continue the study due to toxicity in February 2013. At that time, recruitment to the high-dose group was stopped from the protocol. The relative dose intensity (RDI) for S-1 in the low- and high-dose groups were 49.8 and 48.7% (p = 0.712), and that for oxaliplatin was 75.9 and 73.0% (p = 0.528), respectively. The rates of discontinuation due to toxicity were 60 and 53.8% in the low- and high-dose groups, respectively, with no marked difference noted between the groups (p = 0.747). The frequency of grade ≥ 3 common adverse events was neutropenia (23.3%/23.1%), diarrhea (13.3%/15.4%), and peripheral sensory neuropathy (6.7%/7.7%). The disease-free survival (DFS) at 3years was 52.9% in the low-dose group, which was not significantly different from that in the high-dose group (46.2%; p = 0.705). SOX regimens as adjuvant therapy after hepatectomy for CRCLM had high rates of discontinuation due to toxicity in both groups. In particular, the RDI of S-1 was < 50%. Therefore, the SOX regimen is not recommended as adjuvant chemotherapy after hepatectomy for CRCLM.

Effect of autologous lymphocytes combined with chemotherapy as the first-line treatment of advanced gastric cancer.

4037 Background: To evaluate the safety and initial efficacy of adoptive cell therapy (ACT) combined with SOX in first-line treatment of locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma. Methods: In this single-arm, single-center exploratory trial, patients with histologically confirmed locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma were randomly assigned (1:1) to receive ACT in combination with S-1 and oxaliplatin (SOX) or SOX alone. The primary endpoint was the incidence of adverse events (AEs). Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: Fifty-nine patients were enrolled in the study between November 20, 2014 and September 6, 2017. 31 patients received ACT combined with SOX (ACT-SOX) and 28 patients received SOX. The most common AEs in both groups were gastrointestinal reaction, leucopenia, neutropenia, anemia, thrombocytopenia, hyperbilirubinemia and elevated aspartate transaminase concentration, with a higher incidence in the SOX group. The median PFS for ACT-SOX and SOX were 6.9 and 4.9 months respectively (HR 0.80, p=0.45), and the median OS were 17.8 and 9.75 months (HR 0.76, p=0.34). Patients who received more than three injections of specific lymphocyte subsets benefited the most from combination therapy. Cox univariate and multivariate analysis showed that tumor metastasis to more than two organs was the main risk factor for PFS and OS. 29 patients in the ACT-SOX group and 25 in the SOX group had measurable lesions. The ORR of ACT-SOX group and SOX group was 55.2% and 32.0%, and DCR of two groups was 93.1% and 88.0%. Conclusions: The safety of ACT-SOX in first-line treatment of patients with locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma is good. Compared with SOX alone, although the PFS and OS of ACT-SOX did not reach statistical difference, it could further extend the time of PFS and OS, and the absolute improvement time of OS was about 8.05 months. Continuous benefit of ACT-SOX was observed through long-term follow-up. Clinical trial information: NCT02504229 .

Safety and efficacy of tislelizumab plus chemotherapy versus chemotherapy alone as neoadjuvant treatment for patients with locally advanced gastric cancer: real-world experience with a consecutive patient cohort.

Immunotherapy plus chemotherapy has recently been applied in the neoadjuvant treatment for locally advanced gastric cancer (LAGC), while its superiority over neoadjuvant chemotherapy (NACT) alone remains to be explored. This study explored the safety and efficacy of NACT plus tislelizumab in patients with LAGC. The data on patients with LAGC who received NACT combined with radical gastrectomy and NACT plus tislelizumab followed by radical gastrectomy was retrospectively collected. Clinicopathological characteristics of the two groups were compared. A total of 119 and 50 patients with gastric cancer treated with NACT and NACT plus tislelizumab, respectively, were enrolled. No significant difference was found between the baseline data of the two groups. The operative time (210.5 ± 70.4min vs. 237.6 ± 68.4min, P=0.732), intraoperative blood loss (157.8 ± 75.9ml vs. 149.1 ± 92.5ml, P=0.609), and number of dissected lymph nodes (24.7 ± 9.3 vs. 28.1 ± 10.3, P=0.195) was not statistically different between the two groups. In comparison to the NACT plus tislelizumab group, the R0 resection rate (100% vs. 89.9%, P=0.019) and pathologic complete response rate (26.0% vs. 3.4%, P<0.001) were significantly lower in the NACT group. The postoperative complication rates were 24.4% and 26.0% in the NACT and NACT plus tislelizumab groups with no significant difference (P=0.823). In subgroup analysis, tumor regression grade (TRG) (TRG 3: 72.3% vs. 23.5%, P<0.001) and ypN stage (stages 2-3: 46.8% vs. 5.9%, P=0.003) in the NACT group were significantly higher compared with the NACT plus tislelizumab group in esophagogastric junction carcinoma. Compared with the S-1 and oxaliplatin (SOX) or 5-fluorouracil, folinic acid, and oxaliplatin (FOLFOX) NACT regimen, NACT plus tislelizumab significantly improved the efficacy and R0 resection rate of LAGC without increasing the incidence of perioperative complications, particularly in esophagogastric junction carcinoma.

Exploratory randomized phase II trial for optimizing treatment dosage and duration of adjuvant S-1 plus oxaliplatin in patients with stage III colon cancer: YCOG1402 (SOAP trial).

Conventionally, the recommended duration of adjuvant chemotherapy of colon cancer had been 6 months. The IDEA Collaboration suggested that shortening capecitabin and oxaliplatin (CAPOX) adjuvant chemotherapy may be possible. S-1 and oxaliplatin (SOX) treatment is standard treatment in metastatic colorectal cancer in Japan. The aim of this study was to optimize treatment dosage and duration of adjuvant SOX in stage III colon cancer. This trial was as open-label multi-center randomized phase II study. Patients with stage III colon cancer were randomly assigned to 3 months or 6 months of adjuvant SOX treatment in different doses: 130 mg/m2 (3 months) or 100 mg/m2 (6 months) of oxaliplatin. The primary endpoint was 3-year disease-free survival (DFS) and the null hypothesis for the primary endpoint was that the 3-year DFS was ≤72% in each arm and was tested with a one-sided significance level of 10%. Eighty-two patients were assigned to the 6 months arm and 81 to the 3 months arm. The 3-year DFS was 75.0% (80% CI 67.95-80.72, p = 0.282) in the 6 months arm and 76.9% (80% CI 70.1-82.38, p = 0.171) in the 3 months arm. Treatment completion rate and relative dose intensity (RDI) were higher in 3 months than 6 months arm. The adverse events (AE) were similar in both arms. The 3-year DFS was not significantly superior to null hypothesis in both 3 months and 6 months arms for the stage III colon cancer. Primary endpoint was not achieved. The SOX regimen was not feasible in long-term outcomes.

SOX plus bevacizumab versus SOX plus cetuximab as initial treatment of recurrent advanced colorectal cancer with wild-type KRAS (MCSGO-1107 study): A phase II randomized study.

136 Background: Although clinical outcomes of chemotherapy in patients with locally advanced or metastatic colorectal cancer (CRC) have improved over the last decade, the standard-of-care chemotherapy regimens for patients with unresectable RAS wild-type CRC remain to be discussed. The aim of this study was to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated, unresectable, locally advanced, or metastatic CRC with wild-type KRAS. Methods: This phase II, randomized, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated, unresectable, locally advanced, or metastatic CRC with wild-type KRAS. Forty-five patients were enrolled in this study between February 2012 and October 2016. Results: The overall response rate (ORR) for the SOX+B-mab group was 59.1%, whereas that for the SOX+C-mab group was 43.5% (p = 0.29). The disease control rate (DCR) for the SOX+B-mab group was 90.9%, whereas that of the SOX+C-mab group was 91.3% (p = 0.96). For all patients, median OS were 25.3 months (95% CI: 16.5–39.4 months) in the SOX+B-mab group and 15.5 months (95% CI: 7.30–30.4 months, p = 0.167) in the SOX+C-mab group. Median PFS were 11.7 months (95% CI: 7.37–18.2 months) in the SOX+B-mab group and 5.5 months (95% CI: 3.36–10.1 months, p = 0.077) in the SOX+C-mab group. In the SOX+B-mab group, OS and PFS were not significantly different with and without early tumor shrinkage (ETS). However, in the SOX+C-mab group, patients with ETS had significantly better OS (30.4 months [95% CI: 8.0–44.3 months, p = 0.032]) and PFS (12.0 months [95% CI: 5.1–19.7 months, p = 0.003]) than those without ETS. Conclusions: The safety and efficacy of SOX+B-mab and SOX+C-mab as initial treatment for unresectable CRC with wild-type KRAS were almost the same. ETS was more correlated with PFS in the SOX+C-mab group than in the SOX+B-mab group, suggesting consideration of treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen. Clinical trial information: UMIN000006706 .

POF (paclitaxel/oxaliplatin/5-fluorouracil/leucovorin) vs. SOX/CAPOX/FOLFOX as a postoperative adjuvant chemotherapy for curatively resected stage III gastric cancer: Study protocol for a randomized controlled trial, FNF-014 trial.

BackgroundPostoperative chemotherapy is a standard treatment for stage II and III gastric cancer in Asia. With regard to single-agent or doublet, the need for improvement has consistently been pointed out because of the relatively poor outcome for patients with stage III gastric cancer. Triplet has shown significant survival benefits in the perioperative setting. We conducted a randomized, multicenter, phase III study to compare triplet to doublet regimens for patients with stage III gastric cancer.MethodsThis is currently enrolling patients (n = 230) with pathologic stage III gastric cancer after D2 lymph node dissection and achieved R0 resection. Patients are randomized 1:1 and stratified by tumor stage (IIIA, IIIB, or IIIC, AJCC 8th) into POF or SOX/CAPOX/FOLFOX. S-1 and oxaliplatin (SOX): oxaliplatin 130 mg/m2 on day 1, oral S-1 80–120 mg/m2 divided by two on days 1–14 every 21 days for 8 cycles. Capecitabine and oxaliplatin (CAPOX): oxaliplatin 130 mg/m2 on day 1, oral capecitabine 1000 mg/m2 twice daily on days 1–14 every 21 days for 8 cycles. Folinic acid (or leucovorin), 5-fluorouracil and oxaliplatin (FOLFOX): oxaliplatin 85 mg/m2, levo-leucovorin 200 mg/m2, and 5-fluorouracil (5-FU) 400 mg/m2 bolus on day 1, then 5-FU 2400 mg/m2 continuous infusion over 46 h, every 14 days for 12 cycles. Three doublets were chosen by the clinicians. Paclitaxel, oxaliplatin, 5-fluorouracil, and leucovorin (POF): paclitaxel 135 mg/m2, followed by FOLFOX omitted 5-FU bolus, every 14 days for 12 cycles. The primary end point is 3-year disease-free survival (3-year-DFS). Secondary end points are overall survival (OS) and safety (any adverse event).DiscussionThe results of this study will help establish postoperative clinical evidence for patients with locally advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT0378826].

Efficacy of AS versus SOX regimen as first-line chemotherapy for gastric cancer patients with peritoneal metastasis: a real-world study

BackgroundTo compare the prognosis of first-line systemic chemotherapy of AS (Albumin-bound paclitaxel and S-1) versus SOX (S-1 and oxaliplatin) regimen in Chinese gastric cancer patients with peritoneal metastasis.MethodsThis was a real-world study of gastric cancer patients with peritoneal metastasis who have been treated with AS or SOX regimen as first-line chemotherapy. Patients were matched by the method of propensity score matching (PSM). The primary and secondary endpoints were overall survival (OS) and progress-free survival (PFS).ResultsA total of 108 gastric cancer patients with peritoneal metastasis were enrolled after PSM analysis. There was no significant difference between AS and SOX regimen based on gender, age, ascites, treatment cycles, gastric cancer resection, received checkpoint inhibitors, and HER-2 expression after PSM analysis. The median OS (14.13 vs. 11.17 months, p = 0.0356) and median PFS (10.30 vs. 6.70 months, p = 0.0003) of patients who received AS regimen were longer than those treated by SOX regimen as first-line systemic chemotherapy. In sub-group analysis, the median OS and median PFS were longer for patients in AS regimen than SOX regimen in Lauren diffuse type. The occurrence of toxicity between the two groups was shown no significant difference.ConclusionsThe results verified that AS regimen was more effective than SOX chemotherapy in gastric cancer patients with peritoneal metastasis, especially in Lauren diffuse type.

CT-Based Radiomics Showing Generalization to Predict Tumor Regression Grade for Advanced Gastric Cancer Treated With Neoadjuvant Chemotherapy.

ObjectiveThe aim of this study was to develop and validate a radiomics model to predict treatment response in patients with advanced gastric cancer (AGC) sensitive to neoadjuvant therapies and verify its generalization among different regimens, including neoadjuvant chemotherapy (NAC) and molecular targeted therapy.Materials and MethodsA total of 373 patients with AGC receiving neoadjuvant therapies were enrolled from five cohorts. Four cohorts of patients received different regimens of NAC, including three retrospective cohorts (training cohort and internal and external validation cohorts) and a prospective Dragon III cohort (NCT03636893). Another prospective SOXA (apatinib in combination with S-1 and oxaliplatin) cohort received neoadjuvant molecular targeted therapy (ChiCTR-OPC-16010061). All patients underwent computed tomography before treatment, and thereafter, tumor regression grade (TRG) was assessed. The primary tumor was delineated, and 2,452 radiomics features were extracted for each patient. Mutual information and random forest were used for dimensionality reduction and modeling. The performance of the radiomics model to predict TRG under different neoadjuvant therapies was evaluated.ResultsThere were 28 radiomics features selected. The radiomics model showed generalization to predict TRG for AGC patients across different NAC regimens, with areas under the curve (AUCs) (95% interval confidence) of 0.82 (0.76~0.90), 0.77 (0.63~0.91), 0.78 (0.66~0.89), and 0.72 (0.66~0.89) in the four cohorts, with no statistical difference observed (all p > 0.05). However, the radiomics model showed poor predictive value on the SOXA cohort [AUC, 0.50 (0.27~0.73)], which was significantly worse than that in the training cohort (p = 0.010).ConclusionRadiomics is generalizable to predict TRG for AGC patients receiving NAC treatments, which is beneficial to transform appropriate treatment, especially for those insensitive to NAC.

Efficacy of Different Number of XELOX or SOX Chemotherapy Cycles After D2 Resection for Stage III Gastric Cancer

PurposeWe aimed to explore whether the prognosis of patients treated with capecitabine and oxaliplatin (XELOX) or S-1 and oxaliplatin (SOX) regimens who received fewer cycles of chemotherapy after D2 radical resection for gastric cancer (GC) would be non-inferior to that of patients who received the standard number of cycles of chemotherapy.Materials and MethodsData on patients who received XELOX or SOX chemotherapy after undergoing D2 radical resection at Harbin Medical University Cancer Hospital between January 2011 and May 2016 were collected.ResultsIn patients who received 4, 6, and 8 cycles of chemotherapy, the 5-year overall survival (OS) rates were 59.4%, 64.8%, and 62.7%, respectively. Compared to patients who received 4 cycles of chemotherapy, those who received 6 cycles (hazard ratio [HR], 0.882; 95% confidence interval [CI], 0.599–1.299; P=0.52) or 8 cycles (HR, 0.882; 95% CI, 0.533–1.458; P=0.62) of chemotherapy did not exhibit significantly prolonged OS. The 3-year disease-free survival (DFS) rate of patients who received 4, 6, and 8 cycles of chemotherapy was 62.1%, 67.2%, and 60.8%, respectively. Compared to patients who received 4 cycles of chemotherapy, those who received 6 cycles (HR, 0.835; 95% CI, 0.572–1.221; P=0.35) or 8 cycles (HR, 0.972; 95% CI, 0.606–1.558; P=0.91) of chemotherapy did not show significantly prolonged DFS. However, the 3-year DFS and 5-year OS rates of patients who received 6 cycles of chemotherapy appeared to be superior to those of patients who received 4 and 8 cycles of chemotherapy.ConclusionsFor patients with stage III GC, 4 to 6 cycles of XELOX or SOX chemotherapy may be a favorable option. This study provides a rationale for further randomized clinical trials.

Randomized phase II study of SOX+B-mab versus SOX+C-mab in patients with previously untreated recurrent advanced colorectal cancer with wild-type KRAS (MCSGO-1107 study)

BackgroundAlthough chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated. This study aimed to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS.MethodsThis randomized phase II, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled.ResultsOverall response rates were 59.1 and 43.5% (p = 0.29) and disease control rates were 90.9 and 91.3% (p = 0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR = 0.607, p = 0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR = 0.558, p = 0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p = 0.032 and p = 0.003, respectively).ConclusionsThe efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen.Trial registrationUMIN Clinical Trials Registry (UMIN000006706).Date of registration: NOV/11/2011.URL of trial registry record:https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920

Randomized phase II study comparing the efficacy and safety of SOX versus mFOLFOX6 as neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer (KSCC1301)

BackgroundPreoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT.MethodsPatients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.ResultsFrom September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9–83.6) and 73.4% (95% CI 58.7–83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414–1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable.ConclusionWe demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.Trial registrationDate of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J

Prognosis of Adjuvant SOX vs XELOX Chemotherapy for Gastric Cancer After D2 Gastrectomy in Chinese Patients.

IntroductionTo compare the prognosis of adjuvant SOX (S-1 and oxaliplatin) vs XELOX (capecitabine and oxaliplatin) chemotherapy in Chinese patients with gastric cancer (GC) after D2 gastrectomy.MethodsThis was a real-world study of patients with GC (stages II–III) who underwent D2 gastrectomy and received adjuvant SOX or XELOX between 01/2010 and 06/2017 in Zhongshan Hospital affiliated to Fudan University. The patients were matched by propensity score matching. The primary and secondary endpoints were disease-free survival (DFS) and overall survival (OS), respectively. Adverse events (AEs) were compared.ResultsA total of 552 patients were included. The median follow-up time was 24.9 months. There were no differences in DFS (median, 44.4 vs 41.2 months; HR=1.17, 95% CI: 0.92–1.48) and OS (median, 61.5 vs 65.3 months; HR=1.01, 95% CI: 0.73–1.39) between the XELOX and SOX groups. Both DFS and OS had no significant differences between SOX and XELOX for all subgroups based on sex (P=0.949, P=0.990), age (P=0.303, P=0.392), Lauren type (P=0.362, P=0.573), type of gastrectomy (P=0.607 P=0.989), and pathological TNM stage (P=0.899, P=0.888). A total of 86 patients in the SOX subgroup (34.2%) experienced AEs, similar to the rate found in the XELOX subgroup (104 patients or 41.4%; P=0.098).DiscussionThe results suggested that adjuvant SOX chemotherapy has similar survival benefits compared to XELOX chemotherapy in Chinese patients with pathological stage II or III GC after D2 gastrectomy.

Multiple liver metastases with synchronous gastric and transverse colon cancer diagnosed by gastric perforation successfully treated by SOX plus bevacizumab and completely resected by surgery: a case report

BackgroundSynchronous double cancer of the colon and stomach accompanied by liver metastasis is rare. It is often difficult to determine an appropriate treatment strategy for multiple liver metastases of synchronous gastric cancer and colorectal cancer. Multidisciplinary treatment is required based on the progression and location of each tumor and chemotherapy for complete resection.Case presentationA 57-year-old male who complained of acute abdominal pain and fever visited his local hospital. He underwent emergent surgery for peritonitis caused by a gastric perforation. The cytodiagnosis of ascites did not show any tumor cells. There was a liver metastasis in the lateral segment of the liver. We performed a primary closure of the defect and then applied an omentum flap. After surgery, the patient was diagnosed as having synchronous cStage IV transverse colon cancer with multiple liver metastases and cStage IIB gastric cancer. The [18F]-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed 18F-FDG uptake by the colon tumor and multiple liver metastases, but there was no uptake in the gastric tumor or lymph nodes. We retrospectively reevaluated the CT findings from a local hospital and detected a liver nodule in segment 2/3 (from 35 to 60 mm) and segment 6 (from 26 to 57 mm), and the tumors had dramatically grown in size in only 2 months. Because complete tumor resection would be difficult, S-1 and oxaliplatin (SOX) plus bevacizumab therapy was started to control tumor progression. After 20 courses of chemotherapy, the clinical diagnosis was ycStage IV transverse colon cancer and ycStage IIa gastric cancer. We planned a two-step procedure to completely resect the primary tumors and multiple liver metastases. We first performed a laparoscopic right-colon resection+D3 lymphadenectomy and open distal gastrectomy+D2 lymphadenectomy. The patient was discharged home on postoperative day 18. After 1 month, we performed open liver resection. The pathological findings showed that the transverse colon was ypT2 (MP) with grade 2 therapeutic effects and that there were no atypical cells in the gastric tumor and multiple liver nodules (pathological complete response).ConclusionThe SOX plus bevacizumab regimen could be an option for controlling tumor progression in synchronous double cancer of the colon and stomach with liver metastasis and led to the complete resection of such tumors.

Retrospective Analysis of S-1 plus Bevacizumab as Maintenance Therapy after Induction of S-1 and Oxaliplatin (SOX) plus Bevacizumab as First-Line Chemotherapy in Patients with Metastatic Colorectal Cancer

Background: The SOFT study was a phase III trial designed to validate the non-inferiority of S-1 and oxaliplatin (SOX) plus bevacizumab to mFOLFOX6 plus bevacizumab in terms of PFS in patients with metastatic colorectal cancer (mCRC) who had not previously received chemotherapy. In this study, we retrospectively reviewed cases in which S-1 plus bevacizumab as maintenance therapy after induction of S-1 and Oxaliplatin (SOX) plus bevacizumab as first-line chemotherapy in patients with metastatic colorectal cancer was applied in order to evaluate its efficacy and safety in clinical practice. Material and method: Among the 40 patients with mCRC at the Fuchu Hospital who received SOX plus bevacizumab as a first line treatment between August 2013 and December 2018. The eligible patients had histologically confirmed mCRC. On day 1 of each 3-week period during the study, patients in the SOX plus bevacizumab received a 7.5 mg/kg intravenous infusion of bevacizumab, followed by an intravenous infusion of 130 mg/m2 oxaliplatin. S-1 (40 - 60 mg) was administered orally two times per day from after dinner on day 1 to after breakfast on day 15, followed by a 7-day rest. Results: The median PFS was 15.0 months and median OS was 36.0 months. The response rate (RR: complete pus partial response) was 85.0%, and the disease control rate (DCR: RR plus stable disease) was 92.5%. The most common adverse events with SOX plus bevacizumab were hypertension (50%), neurosensory toxicity (50%), anorexia (32.5%), fatigue (45%), pigmentation (39%), Neutrophil count decreased (30%), and platelet count decreased (40%). The most common grade 3/4 adverse events were neurosensory toxicity (5%) and fatigue (9%). Conclusion: This study revealed that the survival benefit of S-1 and oxaliplatin (SOX) plus bevacizumab in Japanese patients with mCRC was like that observed in previous clinical trials. Therefore, S-1 and oxaliplatin (SOX) plus bevacizumab can be considered as routine first-line treatment option for patients with mCRC.

A pathological complete response by chemotherapy with S-1 and oxaliplatin for a locally advanced duodenal adenocarcinoma in Lynch syndrome: a case report

BackgroundAlthough primary duodenal adenocarcinoma (DA) is a rare malignancy representing ~ 0.5% of all gastrointestinal cancers, the incidence of DA is more frequent in Lynch syndrome. Because of its rarity, treatment strategies or optimal chemotherapeutic regimens have not been clearly defined for advanced DA.Case presentationA 72-year-old woman with Lynch syndrome visited our hospital with a right upper abdominal pain. Computed tomography (CT) showed wall thickness with enhancement in the second portion of the duodenum and adjacent abdominal wall, which suggested direct tumor invasion to the abdominal wall. Upper gastrointestinal endoscopy (UGE) showed a large ulcerative tumor in the second portion of the duodenum, and histological analysis revealed a poorly differentiated adenocarcinoma. A cT4N0M0, cStage IIB (Union for International Control Cancer TNM staging) DA was diagnosed. After three courses of chemotherapy with S-1 and oxaliplatin (SOX), follow-up CT and UGE showed shrinkage of the duodenal tumor. Therefore, the patient underwent pancreaticoduodenectomy with lymph node dissection with curative intent. Histological examination showed a pathological complete response to SOX therapy. The postoperative course was uneventful, and the patient was discharged on postoperative day 29. The patient received no adjuvant chemotherapy, and there has been no evidence of recurrence 6 months after the operation.ConclusionsSOX therapy provided a remarkable response and can be an optimal chemotherapeutic regimen for advanced DA in Lynch syndrome.

Final analysis of survival outcomes in the KSCC1501A trial of up-front therapy for HER2-negative advanced gastric cancer

Abstract Background According to the results of the randomized phase III study, G-SOX, the combination of S-1 and oxaliplatin (SOX) is as effective as the combination of S-1 and cisplatin for the treatment of HER2-negative advanced gastric cancer (AGC), and also has a favorable safety profile. In this trial, the dose of oxaliplatin tested was 100 mg/m2; however, the dose of 130 mg/m2 is covered by insurance in Japan, based on the results of the pivotal global study. Therefore, the efficacy and safety of the SOX regimen with oxaliplatin 130 mg/m2 (SOX130) remains to be elucidated. In this study, we conducted the final analysis of the survival outcomes in a phase II trial to assess the efficacy and safety of SOX130 in HER2-negative AGC. Methods Patients with HER2-negative AGC or recurrent gastric cancer received 80 mg/m2 S-1 per day orally on days 1-14, and 130 mg/m2 oxaliplatin intravenously, on day 1 of each 21-day cycle, until criteria for treatment withdrawal were fulfilled. The primary endpoint was the response rate (RR), and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AE) were recorded according to CTCAE version 4.0. Results In this study, 71 patients were enrolled from June 2015 to November 2016, but 8 patients were excluded owing to ineligibility. Therefore, the efficacy and safety analyses were finally conducted among 63 patients. The confirmed RR, assessed by an independent review committee, was 46.0% (95% confidence interval [CI]: 34.3-58.2), and the disease control rate was 77.8% (95% CI: 66.1-86.3). The median PFS and OS were 4.9 months (95% CI: 4.2-7.1) and 14.8 months (95% CI: 11.1-18.9), respectively. The incidence rates of grade 3 or 4 AE were as follows: neutropenia, 9.5%; thrombocytopenia, 11.1%; anemia, 6.3%; sensory neuropathy, 12.7%; anorexia, 19.0%; and diarrhea, 6.3%. Conclusions SOX130 showed favorable survival outcomes and an acceptable safety profile in the treatment of HER2-negative AGC.

Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT

BackgroundThe prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma.MethodsEligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy.DiscussionThe results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma.Trial registrationClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.