Capecitabine Plus Oxaliplatin Research Articles

Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models

The development of targeted cancer therapies based on monoclonal antibodies against tumor-associated antigens has progressed markedly over recent decades. This approach is dependent on the identification of tumor-specific, normal tissue-sparing antigenic targets. The transmembrane protein claudin-18 splice variant 2 (CLDN18.2) is frequently and preferentially displayed on the surface of primary gastric adenocarcinomas, making it a promising monoclonal antibody target. Phase 3 studies of zolbetuximab, a chimeric immunoglobulin G1 monoclonal antibody targeting CLDN18.2, combined with 5-fluorouracil/leucovorin plus oxaliplatin (modified FOLFOX6) or capecitabine plus oxaliplatin (CAPOX) in advanced or metastatic first-line gastric or gastroesophageal junction (G/GEJ) adenocarcinoma have demonstrated favorable clinical results with zolbetuximab. In studies using xenograft or syngeneic models with gastric cancer cell lines, zolbetuximab mediated death of CLDN18.2-positive human cancer cell lines via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro and demonstrated anti-tumor efficacy as monotherapy and combined with chemotherapy in vivo. Mice treated with zolbetuximab plus chemotherapy displayed a significantly higher frequency of tumor-infiltrating CD8+ T cells versus vehicle/isotype control-treated mice. Furthermore, zolbetuximab combined with an anti-mouse programmed cell death-1 antibody more potently inhibited tumor growth compared with either agent alone. These results support the potential of zolbetuximab as a novel treatment option for G/GEJ adenocarcinoma.

Olaparib with or without bevacizumab versus bevacizumab plus a fluoropyrimidine as maintenance therapy in advanced colorectal cancer: The randomized phase 3 LYNK-003 study

BackgroundThe randomized, open-label, phase III LYNK-003 study assessed the efficacy of first-line maintenance olaparib, alone or in combination with bevacizumab, versus bevacizumab plus a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer (mCRC). We present results of the prespecified interim futility analysis. MethodsEligible participants were ≥18 years of age with unresectable or mCRC that had not progressed after induction with first-line bevacizumab plus 5-fluorouracil plus oxaliplatin plus leucovorin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). Participants were randomly assigned 1:1:1 to olaparib plus bevacizumab, olaparib alone, or bevacizumab plus a fluoropyrimidine (5-fluorouracil or capecitabine). The primary end point was progression-free survival (PFS) per RECIST v1.1 by central review. ResultsBetween August 2020 and May 2022, 309 participants were assigned to olaparib plus bevacizumab (n = 104), olaparib (n = 107), or bevacizumab plus fluoropyrimidine (n = 98). At interim analysis, with a median follow-up of 7.6 months (range 0.1–19.7 months), the median PFS was 3.7 months (95% CI 2.8–5.3) with olaparib plus bevacizumab (HR 1.52; 95% CI 1.02–2.27; P = 0.982) and 3.5 months (95% CI 2.0–3.7) with olaparib (HR 2.11; 95% CI 1.39–3.18; P = 0.999) versus 5.6 months (95% CI 3.8–5.9) with bevacizumab plus fluoropyrimidine. Treatment-related adverse events occurred in 64 (62%), 52 (50%), and 57 (59%) participants, respectively. There were no treatment-related deaths. ConclusionThe LYNK-003 study was stopped prematurely as criteria for futility were met. Maintenance olaparib with or without bevacizumab did not demonstrate clinical efficacy compared with bevacizumab plus a fluoropyrimidine. ClinicalTrials.gov registrationNCT04456699

Study protocol of short-course radiotherapy combined with CAPOX and PD-1 inhibitor for locally advanced colon cancer: a randomised, prospective, multicentre, phase II trial (TORCH-C)

IntroductionThe preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1...

Association of Geriatric Nutritional Risk Index With Adverse Event and Treatment Duration in Adjuvant Chemotherapy for Patients With Colorectal Cancer.

In recent years, the Geriatric Nutritional Risk Index (GNRI) has been reported as a predictor of prognosis in many patients with cancer. This study investigated the association of preoperative GNRI with the occurrence of adverse events and duration of treatment with capecitabine plus oxaliplatin (CAPOX), a postoperative adjuvant chemotherapy, in 59 patients with colorectal cancer from September 2019 to April 2022. A cut-off value of 100.9 was used to categorize patients into high and low GNRI groups. The incidence of grade ≥2 leukopenia (p=0.03), and all grades peripheral neuropathy (p=0.04) were significantly more frequent in the low GNRI group. Analysis of factors influencing treatment duration by univariate and multivariate Cox regression proportional hazards models showed a significant difference in GNRI (p=0.0097). GNRI, a nutritional indicator assessed before the start of treatment, influences the occurrence of adverse events and duration of treatment with CAPOX as adjuvant chemotherapy. To complete CAPOX therapy, preoperatively, it is important to assess the patients' nutritional status using the GNRI and to actively intervene in nutritional therapy.

Evaluation of the Leftover Capecitabine Tablets in Adjuvant CAPOX Chemotherapy for Gastric Cancer

Since it is important that patients take their oral anticancer therapy as prescribed, pharmacists need to assess adherence. In addition, oral anticancer drugs are expensive, and reuse of leftover drugs at outpatient pharmacy clinics is useful in reducing drug costs. The present study aimed to clarify when and why patients have leftover capecitabine tablets, and the cost of leftover capecitabine tablets reused at an outpatient pharmacy clinic, focusing on adjuvant capecitabine plus oxaliplatin (CAPOX) chemotherapy for gastric cancer. We retrospectively studied patients who received adjuvant CAPOX chemotherapy for gastric cancer between November 1, 2015, and April 30, 2021, at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The cost of leftover capecitabine reused by pharmacists was calculated based on the National Health Insurance drug price standard for the study period. This study included 64 patients who received adjuvant CAPOX chemotherapy. Thirty-seven patients had 152 leftover capecitabine tablets. The most common reasons for leftover capecitabine tablets were nausea and vomiting (21.7%), missed doses (18.4%), and diarrhea (13.2%). The leftover capecitabine tablets for 25 patients were reused at the outpatient pharmacy clinic at a cost of JPY 604142.8 (JPY 24165.7 per patient). The study results suggest that evaluating capecitabine adherence and the reasons for leftover capecitabine tablets at outpatient pharmacy clinics as well as reusing leftover medication can contribute to reducing drug costs.

Impact of the IDEA collaboration study on practice patterns of adjuvant chemotherapy in patients with stage III colon cancer: A population-based study.

533 Background: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration showed no significant clinical difference in outcomes in patients with stage III colon cancer treated with 3 months versus 6 months of oxaliplatin-based adjuvant chemotherapy (O-ACT). We aimed to assess the change in practice patterns of ACT before and after publication of the IDEA study. Methods: This was a retrospective, population-based, cohort study of patients ≥ 18 years of age diagnosed with stage III colon cancer between January 1, 2012 and December 31, 2021 in Alberta, Canada. Eligible patients received >1 dose of ACT. Patients were divided into two groups; pre-IDEA (diagnosed prior to March 31, 2018) and post-IDEA (diagnosed on or after April 1, 2018). Treatment duration was categorized as short (<4.5 months) and long (≥4.5 months). The primary outcome was the median duration and type of ACT and factors associated with a shorter duration of ACT. Two-year overall survival (OS) and cancer-specific survival (CSS) were secondary outcomes. Results: We identified a total of 735 patients. Median age at diagnosis was 64 years (range 27-90 years) and 52.8% (N=388) were male. 48.8% (N=359) patients had had pT4 and/or pN2 disease. 78% (N=572) received O-ACT. In the post-IDEA era, the use of capecitabine plus oxaliplatin (CAPOX) ACT increased (23.0% to 50.9%, p<0.001) and median duration of O-ACT was significantly shorter (2.7 vs 4.8 months, p<0.001). On multivariable logistic regression, factors associated with shorter duration of ACT included treatment in the post-IDEA era (odds ratio [OR] 1.85, p=0.007), no pT4 and/or pN2 disease (OR 1.6, p=0.02), and receipt of CAPOX ACT (OR 2.7, p<0.001). Characteristics not significantly associated with ACT duration included age, sex, residence rurality, neighborhood income, and comorbidity index. The 2-year OS and CSS was similar in the pre-IDEA and post-IDEA eras (OS 95% vs 93%, p=0.29; CSS 96% vs 96%, p=0.30). Neither time era or treatment duration were independently associated with OS or CSS in multivariable models. Conclusions: Our study is one of the first that shows that the results of the IDEA trial have been largely adopted in clinical practice with shorter duration of ACT and increased use of CAPOX ACT in low-risk stage III colon cancer using population-based data.

Comparison of adjuvant capecitabine plus oxaliplatin (CAPOX) versus S-1 after gastrectomy: a population-based cohort study using a nationwide claims database

Although both capecitabine plus oxaliplatin (CAPOX) and S-1 are accepted as adjuvant chemotherapy following gastrectomy for gastric cancer, the better option between the two is still controversial. We conducted a retrospective nationwide cohort study using data from the National Health Insurance Service of Korea. We included patients who underwent gastrectomy for a primary diagnosis of gastric cancer between January 1, 2013, and December 31, 2018. The study compared the survival outcomes of patients who received postoperative chemotherapy based on S-1 (Arm S) vs. CAPOX (Arm C), as well as other relevant clinical variables such as comorbidity and completion of planned treatment. A total of 6602 patients were included in the analysis, with 4199 in Arm S and 2403 in Arm C. After propensity score matching, the final study population consisted of 2067 patients in each arm. Arm C showed statistically inferior 5-year overall survival (OS) and disease-free survival (DFS) rates compared to Arm S (84.0% vs. 90.0%; p < 0.0001; and 78.4% vs. 86.1%; p < 0.0001). Age (65 ≥ vs. < 65) and the incomplete planned treatment also had a significant negative effect on both OS and DFS. In the multivariable analysis, Arm C still showed worse OS (hazard ratio [HR], 1.609; 95% confidence intervals [CI], 1.339–1.934; p < 0.0001) and DFS (HR, 1.552; 95% CI 1.333–1.807; p < 0.0001) than Arm S. Both S-1 and CAPOX showed excellent efficacy, but this nationwide cohort study suggests that S-1 may be a better option in certain clinical situations.

Comparison of adjuvant capecitabine plus oxaliplatin (CAPOX) versus S-1 in patients with gastric cancer after gastrectomy based on the registry data base on the National Health Insurance Service (NHIS) database in Korea.

e16069 Background: The standard of care for locally advanced gastric cancer in Asia is still upfront gastrectomy with D2 lymph node dissection followed by adjuvant chemotherapy (AC). Both capecitabine plus oxaliplatin (CAPOX) and S-1 are accepted. Which of the two types of chemotherapy is better is still controversial. Methods: For this retrospective nationwide cohort study, data were obtained from the NHIS of Korea. As the NHIS is a single-payer healthcare system, it covers the entire population in the Republic of Korea and it also provides comprehensive information which contains demographic data, healthcare utilization, pharmaceutical prescriptions, and death for each patient. In study population, we included patients who received gastrectomy with a primary diagnosis of gastric cancer which were certified by international classification of disease (ICD) 10th codes of C16.x from January 1st 2013 to December 31th 2018. Survival outcomes of patients who received postoperative chemotherapy were compared based on S-1 (Arm S) vs. CAPOX (Arm C) as well as other relevant clinical variables such as age, sex, co-morbidity and completion of planned treatment. Results: During the study period, 98,556 patients were identified to have undergone both gastric cancer and surgery. After excluding ineligible subjects, a total of 6,602 patients were included in the analysis. Of these, there were 4,199 in Arm S and 2,403 in Arm C, respectively. After propensity score matching, final study population were identified 2,067 in each arm. Arm C showed statistically inferior survival (OS) compared to Arm S (5-year OS rate, 84.0% vs 90.0%, p &lt; 0.0001). Disease-free survival (DFS) was also shorter in Arm C than Arm S (5-year DFS, 78.4% vs 86.1%, p &lt; 0.0001). Age (65 ≥ vs. &lt; 65) and incompleteness of the planned treatment had also significant negative effect on both OS and DFS. Charlson co-morbidity index (≥4 vs. 0-3) was not associated with the difference of OS or DFS. After adjusting with multivariable analysis, Arm C still showed worse OS (HR 1.609, 95% CI, 1.339-1.934, p &lt; 0.0001) and DFS (HR 1.552, 95% CI, 1.333-1.807, p &lt; 0.0001) compared to Arm S. Conclusions: Both S-1 and CAPOX showed excellent efficacy. This nation-wide cohort study suggests that S-1 can be a better option in some clinical situations.

Zolbetuximab + CAPOX Improves Survival in Advanced Gastric/GEJ Cancer

Zolbetuximab + CAPOX Improves Survival in Advanced Gastric/GEJ Cancer

Combining chemotherapy and tislelizumab with preoperative split-course hypofraction radiotherapy for locally advanced rectal cancer: study protocol of a prospective, single-arm, phase II trial

IntroductionShort-course radiotherapy (SCRT) with systemic therapy has the potential to further improve the long-term efficacy in patients with locally advanced rectal cancer (LARC). To maximise the benefits of neoadjuvant therapy...

Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy

The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.

Efficacy of S-1 or Capecitabine Plus Oxaliplatin Adjuvant Chemotherapy for Stage II or III Gastric Cancer after Curative Gastrectomy: A Systematic Review and Meta-Analysis.

Simple SummaryAdjuvant chemotherapy regimens tegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) have predominated, owing to evidence of their remarkable oncologic outcomes, however, there has been a lack of studies on the difference in efficacy between the two regimens. We conducted pairwise meta-analyses comparing the efficacy of S-1 and CAPOX regimens for overall survival (OS) and disease-free survival (DFS) in stage II or III gastric cancer patients. In all stages (stages II and III), the five-year OS was not different between the two regimens (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.78–1.17; p = 0.56). Additionally, the five-year DFS was not different at any stage (HR 1.00, 95% CI 0.85–1.18; p = 0.21). The present meta-analysis showed that five-year OS and DFS for stage II or III gastric cancer patients were comparable between the S-1 and CAPOX adjuvant chemotherapy regimens.Background: Adjuvant chemotherapy (AC) regimens tegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) have predominated, however, there has been a lack of studies on their differences in efficacy. Methods: We conducted pairwise meta-analyses comparing the efficacy of S-1 and CAPOX regimens for overall survival (OS) and disease-free survival (DFS) in stage II or III GC patients. Results: Three studies were enrolled and analyzed using a forest plot for meta-analysis. Two of them were propensity score matching studies, and the remaining one was a retrospective observational study. In all stages, the five-year OS was not different between the two regimens (HR 0.96, 95% CI 0.78–1.17; p = 0.56). Additionally, the 5-year DFS was not different at any stage (HR 1.00, 95% CI 0.85–1.18; p = 0.21). After omitting the retrospective observational study, the five-year OS (HR 1.40, 95% CI 0.53–3.73) and DFS (HR 1.41, 95% CI 0.57–3.44) of S-1 tended to be better in stage II, and the five-year OS (HR 0.81, 95% CI 0.56–1.16) and DFS (HR 0.85, 95% CI 0.63–1.13) of CAPOX tended to be better in stage III, without statistical significance. Conclusions: In the present meta-analysis, the five-year OS and DFS for stage II or III GC patients were comparable between S-1 and CAPOX regimens as AC.

Signet-ring cell carcinoma of the appendix with ganglioneuromatosis: a case report

BackgroundPrimary cancer of the appendix, especially signet-ring cell carcinoma, is an uncommon disease, and it is rarely suspected before surgery. Diffuse intestinal ganglioneuromatosis that is not associated with neurofibromatosis-1 or multiple endocrine neoplasia 2b is also rare. The most frequent symptoms caused by it are changes in bowel habits, abdominal pain, and occlusive episodes.Case presentationThe patient was a 48-year-old woman who had a month-long history of chronic abdominal pain, fullness, constipation, and diarrhoea. Enhanced computed tomography showed a 100-mm irregular swelling in the appendix and thickening of the appendiceal wall with cystic dilatation. Based on a preoperative diagnosis of appendiceal cancer, the patient underwent laparoscopic ileocecal resection with D3 lymph node dissection. Pathological diagnosis revealed a signet-ring cell carcinoma of the appendix with ganglioneuromatosis. The patient completed four courses of capecitabine plus oxaliplatin (CAPEOX) as postoperative adjuvant chemotherapy, and 23-month postoperative outcome was noneventful without recurrence.ConclusionWe report a signet-ring cell carcinoma of the appendix that was detected early because of its presence with ganglioneuromatosis.

Short-course radiotherapy combined with CAPOX and Toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: a randomized, prospective, multicentre, double-arm, phase II trial (TORCH)

BackgroundFor patients with locally advanced (T3-4/N +) rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with total mesorectal resection, which greatly decreases local recurrence but does not improve overall survival. For patients who achieve a complete clinical response (cCR) after nCRT, a “Watch & Wait” (W&W) approach can be received to improve quality of life. Currently, total neoadjuvant therapy (TNT) has been demonstrated to increase the complete response rate and achieve early control of distant metastasis. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and radiotherapy. Thus, for LARC patients, the combination of immunotherapy and TNT is likely to further improve the rate of complete response and prognosis. The disparities between induction therapy and consolidation therapy need to be investigated.MethodsTORCH is a randomized, prospective, multicentre, double-arm, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy in LARC. 130 LARC patients will be treated with the TNT approach and assigned to the consolidation arm and induction arm. The consolidation arm will receive SCRT, followed by 6 cycles of capecitabine plus oxaliplatin (CAPOX) and Toripalimab. The induction arm will first receive 2 cycles of CAPOX and Toripalimab, then receive SCRT, followed by 4 cycles of CAPOX and Toripalimab. Both groups will receive curative surgery or the W&W strategy. The primary endpoint is the complete response rate (rate of pCR plus cCR). The secondary endpoints include the grade 3–4 acute adverse effects rate, 3-year disease-free survival (DFS) rate, 3-year local recurrence-free survival (LRFS) rate, 3-year OS rate, rate of surgical complications and quality of life (QoL) scores. The “pick the winner” method is used to investigate the better treatment regimen. The trial was opened on 13th April 2021, and the first patient was recruited on 6th May 2021.DiscussionTORCH will investigate whether SCRT combined with chemotherapy and Toripalimab can achieve better complete response rates, good tolerance and prognosis in LARC patients. This is the first clinical trial to compare the efficacy of induced immunotherapy and consolidative immunotherapy based on the TNT strategy.Trial registrationTrial Registration Number and Date of Registration: ClinicalTrials.gov NCT04518280, August 15, 2020.

Long-Term Survival Outcomes of Elderly Patients Treated With S-1 or Capecitabine Plus Oxaliplatin for Stage II or III Gastric Cancer: A Multicenter Cohort Study.

PurposeTegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) are standard adjuvant chemotherapies (ACs) administered after gastrectomy to patients with stage II or III gastric cancer. However, the efficacy of AC in elderly patients remains unclear. The objective of this retrospective multicenter cohort study was to compare the efficacies of S-1 and CAPOX AC in patients aged ≥70 years.Materials and MethodsNine hundred eighty-three patients who were treated with AC using S-1 (768 patients) or CAPOX (215 patients) were enrolled in this study. Each patient underwent AC after curative gastrectomy for stage II or III gastric cancer at one of 27 hospitals in the Republic of Korea between January 2012 and December 2013. Relapse-free survival (RFS) and overall survival (OS) were analyzed according to AC regimen and age group.ResultsOf the 983 patients, 254 (25.8%) were elderly. This group had a similar RFS (P=0.099) but significantly poorer OS (p=0.003) compared with the non-elderly group. Subgroup analysis of the non-elderly group revealed no AC-associated differences in survival. Subgroup analysis of the elderly group revealed significantly better survival in the S-1 group than in the CAPOX group (RFS, P<0.001; OS, P<0.001). Multivariate analysis revealed that the CAPOX regimen was an independent poor prognostic factor for RFS (hazard ratio [HR], 1.891; 95% confidence interval [CI], 1.072–3.333; P=0.028) and OS (HR, 2.970; 95% CI, 1.550–5.692; P=0.001).ConclusionsThis multicenter observational cohort study found significant differences in RFS and OS between S-1 and CAPOX AC among patients with gastric cancer aged ≥70 years.

Efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation.

BACKGROUNDAt present, colorectal cancer is routinely treated with adjuvant radiotherapy and chemotherapy postoperatively. The adverse effects (AEs) of chemotherapy usually interrupt the treatment of chemotherapy. Traditional Chinese medicine (TCM) has demonstrated great potential in improving patients' clinical symptoms, regulating the immune function, improving the life quality, and reducing the AEs of chemotherapy.AIMTo observe the clinical efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation.METHODSData from patients diagnosed with colorectal cancer between January 2019 and February 2021 were collected from Liaoning Cancer Hospital and Institute and the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine. Patients receiving the chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) after radical resection of colorectal cancer were prospectively collected and randomly divided into an experimental group and a control group. The experimental group was given Yiqi Jianpi anti-cancer prescription combined with the CAPOX regimen, while the control group was given the CAPOX regimen alone. After six cycles of chemotherapy, the scores of TCM symptoms, Karnofsky performance scale (KPS) score, levels of T-cell subsets, and AEs after chemotherapy of the two groups were compared. RESULTSA total of 70 patients were randomly divided into either an experimental group (n = 35, no dropout) or a control group (n = 33, with 2 dropouts). Compared with the control group, the experimental group improved significantly (P < 0.05) in scores of TCM symptoms, KPS score, levels of T-cell subsets, and AEs of chemotherapy.CONCLUSIONYiqi Jianpi anti-cancer prescription can effectively improve spleen deficiency, regulate the immune function, and alleviate the AEs of chemotherapy, so as to improve the life quality of patients with good therapeutic effects and application prospect in clinical practice.

Clinical biomarkers in adjuvant chemotherapy for gastric cancer after D2 dissection by a pooled analysis of individual patient data from large randomized controlled trials.

Adjuvant therapy for gastric cancer is a standard among the world with no regimen selection criteria. Also, prognostic factors except for tumor staging have not been established. We aimed to identify prognostic and predictive markers for gastric cancer adjuvant therapy from large randomized controlled trials with standard lymph node dissection. Three studies: ACTS-GC, CLASSIC, and SAMIT were found and selected for a pooled analysis, following PRISMA guideline. The integrity of individual participant data (IPD) was verified in the eligible 3527 patients registered, and fixed-effect model was used. The primary endpoint was relapse-free survival (RFS) and the secondary endpoint was overall survival (OS). Age was a significant prognostic factor in addition to tumor stages both in "surgery alone" and "adjuvant" groups. Adjuvant therapy was effective for every TN stage; however, it tended to be more effective in T1-2 than in T3-4. Also, it was more effective in low- or middle-BMI than in high-BMI group with Hazard ratio [HR]s: 0.58, 0.58, and 1.05, respectively. Capecitabine plus oxaliplatin (CAPOX) was more effective than S-1 for T1-2, N2-3, and differentiated type with HRs between 0.59 and 0.70, but with no difference among TNM stages. Combining histology to TN; the HRs in differentiated T1-2 N1-3 groups were between 0.29 and 0.45. For T3-4 N0-1 group, S-1 was likely to be effective, not significant. Age is a significant prognostic factor both in surgery alone and adjuvant group. CAPOX is more effective for differentiated T1-2 tumors with lymph node metastasis.

Association of a Shortened Duration of Adjuvant Chemotherapy With Overall Survival Among Individuals With Stage III Colon Cancer

Several real-world oncology studies have produced findings that contradict those from randomized clinical trials. Such disparities may be associated with methodological shortcomings. To examine the association between a shortened duration of adjuvant chemotherapy among individuals with stage III colon cancer using real-world data. This comparative effectiveness study included individuals diagnosed with stage III colon cancer between January 2004 and December 2015 who initiated adjuvant chemotherapy at oncology clinics within the province of Alberta, Canada. Patients were identified through record linkage of various administrative databases and were followed up until September 2017. Eligibility criteria were modeled after those used in the International Duration Evaluation of Adjuvant (IDEA) trial. A target trial emulation and naive observational analysis were conducted. Results from both cohorts were benchmarked against findings from the IDEA trial. Data analysis was conducted from March to December 2020. A shortened duration of adjuvant 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX) chemotherapy, defined as 3 to 5 months of treatment vs 6 months. Overall survival assessed via vital statistics. The per-protocol hazard ratio (HR) was estimated using a weighted pooled logistic regression model. Subgroup analyses were conducted by treatment regimen (ie, FOLFOX vs CAPOX) and cancer stage (ie, T1-3 and N1 vs T4 or N2). From an initial cohort of 3086 patients, 485 (16%) were eligible for inclusion in the target trial analysis. The median age was 59 years (range, 19-81 years), and 230 (47%) were women. The maximum follow-up was 11.6 years. Median overall survival was not reached. A total of 90 patients (19%) died. The 5-year Kaplan Meier overall survival estimate was 0.79 (95% CI, 0.75-0.84). Estimates from the trial emulation were similar to those from the IDEA trial. For example, a shortened duration of adjuvant chemotherapy was not associated with overall survival among patients prescribed CAPOX in the IDEA trial (HR, 0.96; 95% CI, 0.85-1.08) or in the trial emulation (HR, 0.96; 95% CI, 0.43-2.14). In contrast, the naive observational analysis suggested that a shortened duration of CAPOX was significantly associated with worse survival (HR, 3.33; 95% CI, 1.04-10.65). In this study, the explicit emulation of a target trial better approximated results from an analogous well-conducted randomized clinical trial.

Extending chemotherapy with capecitabine following CAPOX chemotherapy improves survival of Stage 3 gastric carcinoma after radical surgery: a 5-year analysis.

To assess the effectiveness and safety of treatment consisting of extending chemotherapy (ECT) with capecitabine following capecitabine plus oxaliplatin (CAPOX) chemotherapy for stage 3 gastric carcinoma (GC) after D2 gastrectomy. In this retrospective study, we included 214 patients with stage 3 GC who underwent D2 gastrectomy between January 2012 and April 2014. The CAPOX regimen chemotherapy was administrated to all of the patients as adjuvant therapy. The CAPOX regimen consisted of capecitabine (1000 mg/m2, in 2 divided doses for 14 d) and oxaliplatin (130 mg/m2 given on Day 1), repeated every 21 d for 8 cycles. Following CAPOX chemotherapy, 102 of these patients received extending chemotherapy (the ECT group) with capecitabine, whereas 112 patients (the control group) received no ECT. The ECT consisted of capecitabine (1000 mg/m2, in 2 divided doses for 14 d), repeated every 21 d for 8 cycles at most. The chemotherapy was discontinued if unacceptable toxicity or disease progression occurred or upon the request of the patient. All cases were followed up, and overall survival (OS), recurrence-free survival (RFS), and toxicities were compared. The ECT group exhibited a distinctly higher 5-year OS (p=0.0468) and RFS (p=0.0483) than those of the control group. The incidence of hand-foot syndrome was markedly greater in the ECT group (p=0.0043). No toxicity-related death occurred. Extending chemotherapy with capecitabine following the CAPOX regimen chemotherapy provides significant survival benefit for stage 3 GC after D2 gastrectomy.

5-Hydroxytryptamine-3 receptor antagonist and dexamethasone as prophylaxis for chemotherapy-induced nausea and vomiting during moderately emetic chemotherapy for solid tumors: a multicenter, prospective, observational study

BackgroundOf patients receiving moderate emetic risk chemotherapy (MEC), 30–90% experience chemotherapy-induced nausea and vomiting (CINV); however, the optimal antiemetic treatment remains controversial.MethodsIn this multicenter, prospective, observational study of adults treated with MEC while receiving chemotherapy for various cancer types in Japan, the enrolled patients kept diaries documenting CINV. All participants received a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone.ResultsOf the 400 patients enrolled from May 2013 to January 2015, 386 were eligible for evaluation. The median age was 64 (range, 26–84). The overall complete response (CR; no emetic events and no antiemetic measures) rate was 64%. The proportion of patients showing CR was low in the carboplatin (CBDCA)- and oxaliplatin-based chemotherapy groups, especially among women. We showed that the CR rates in men were high in the CBDCA (AUC5) + etoposide (ETP) (80%), capecitabine plus oxaliplatin (CAPOX) (78%), and CBDCA+ paclitaxel (PTX) groups for lung cancer (73%). Total control (TC; no emetic events, no antiemetic measures, and no nausea) and complete control (CC; no emetic events, no antiemetic measures, and less than mild nausea) were achieved in 51 and 61% of patients, respectively. Logistic regression analysis revealed history of motion sickness, history of pregnancy-associated vomiting and CBDCA-based chemotherapy as risk factors for CR and history of motion sickness and history of pregnancy-associated vomiting as risk factors for TC. Additional, Ages ≥65 years is an independent predictive factor for achieving TC.ConclusionsOur data showed that two antiemetics were insufficient to control CINV in patients receiving CBDCA- or oxaliplatin-based chemotherapy. However, two antiemetics may be sufficiently effective for elderly male patients receiving CBDCA (AUC5) + ETP, CBDCA+PTX for lung cancer, or CAPOX. Additionally, we consider that three antiemetics are necessary for women with colorectal cancer receiving CAPOX. Risk factor analysis related to CR showed that CINV prophylaxis in patients treated with CBDCA-based chemotherapy was generally supportive of the guideline-recommended three antiemetics. However, the control of nausea in patients receiving non-CBDCA-based chemotherapy is a key point to note. The further individualization of antiemetic regimens for patients receiving MEC based on both types of chemotherapy regimens and sex is needed.