Adjuvant treatment for gastric cancer: chemotherapy versus radiation.
Ontology highlight
ABSTRACT:
SUBMITTER: Ashraf N
PROVIDER: S-EPMC3780633 | biostudies-other | 2013
REPOSITORIES: biostudies-other
Publications
Adjuvant treatment for gastric cancer: chemotherapy versus radiation.
Ashraf Noman N Hoffe Sarah S Kim Richard R
The oncologist 20130821 9
Gastric cancer is among the leading causes of cancer death worldwide. Surgery is the only curative modality, but mortality remains high because a significant number of patients have recurrence after complete surgical resection. Chemotherapy, radiation, and chemoradiotherapy have all been studied in an attempt to reduce the risk for relapse and improve survival. There is no globally accepted standard of care for resectable gastric cancer, and treatment strategies vary across the world. Postoperat ...[more]
Similar Datasets
Project description:BACKGROUND:Treatment of localized gastric cancer (LGC) consists of surgical resection followed by adjuvant treatment. Both chemoradiation (CRT) and chemotherapy (CT) regimens have shown benefit in survival outcomes versus observation. However, there are few data comparing these approaches. METHODS:This study included consecutive patients with LGC treated at Instituto do Cancer do Estado de Sao Paulo (ICESP) from 2012 to 2015. CRT was based on the INT-0116 regimen and CT consisted of a platinum and fluoropyrimidine doublet. Treatment choice was based on physician preference. Toxicity was evaluated for every cycle. Overall survival (OS) analysis was performed by Kaplan-Meier. A propensity score-matched analysis was performed to minimize selection bias. RESULTS:A total of 309 patients were evaluated, 227 in CRT group and 82 in CT group. The most prevalent grade 3/4 toxicities in CRT and CT groups were: nausea/vomiting (9.25 vs 4.9%), fatigue (9.3% vs 2.4%), mucositis (4.4% vs 1.2%), neutropenia (37.8% vs 20.9%), febrile neutropenia (3.9% vs 0%), anemia (4.3% vs 6.1%), thrombocytopenia (2.6% vs 4.9%), neuropathy (0 vs 2.4%) and hand-foot syndrome (0.4% vs 2.4%). Two grade 5 toxicities (febrile neutropenia and anemia) occurred in CRT group. There was no difference in the pattern of recurrence. After a median follow-up of 23.5 months (CRT) and 20.6 months (CT), there was no difference in OS between groups. CONCLUSIONS:CT and CRT present similar efficacy and tolerability as adjuvant treatment for LGC.
| S-EPMC5883367 | biostudies-literature
Project description:BackgroundStage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence.MethodsIn this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life.ResultsOf the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group.ConclusionsChemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).
| S-EPMC6948006 | biostudies-literature
Project description:Gastric adenocarcinoma most often presents at an advanced stage and overall five-year survival of ∼30%. Pharmacological ascorbate (high-dose IV ascorbate) has been proposed as a promising nontoxic adjuvant to standard radio-chemotherapies in several cancer types. In the current study, pharmacological ascorbate (0.5-2 m M) caused a dose-dependent decrease (70-85% at 2 m M) in clonogenic survival of gastric adenocarcinoma cells (AGS and MNK-45), but was relatively nontoxic to a small intestinal epithelial nonimmortalized human cell isolate (FHs 74 Int). The addition of pharmacological ascorbate (1 m M) to standard radio-chemotherapies [i.e., 5-FU (5 μ M); cisplatin (0.5 μ M); irinotecan (2.5 μ M); carboplatin (5 μ M); paclitaxel (2-4 n M); and X rays (1.8 Gy)] also potentiated gastric cancer clonogenic cell killing [additional decreases were noted with: ascorbate plus 5-FU/radiation (1%); ascorbate plus cisplatin/irinotecan (9-19%); and ascorbate plus paclitaxel/carboplatin (6-7%)]. The gastric cancer cell toxicity and chemosensitization seen with pharmacological ascorbate was dependent on H2O2 and the presence of catalytic metal ions. In addition, pharmacological ascorbate dosing resulted in a concentration-dependent decrease (64% at 20 m M, P ≤ 0.0001) in cancer cell invasion and migration that was inhibited by catalase. Finally, pharmacological ascorbate significantly increased the overall survival of mice with gastric cancer xenografts when used in combination with paclitaxel, carboplatin and radiation ( P = 0.019). These results demonstrate that pharmacological ascorbate is selectively cytotoxic to gastric adenocarcinoma cells (relative to normal intestinal epithelial cells) by a mechanism involving H2O2 and redox active metal ions. Furthermore, pharmacological ascorbate significantly enhances gastric cancer xenograft responses to radio-chemotherapy as well as inhibiting tumor cell migration and invasiveness. Overall, these results support the hypothesis that pharmacological ascorbate can be used as an adjuvant with standard-of-care radio-chemotherapies for the treatment of gastric adenocarcinomas.
| S-EPMC6117840 | biostudies-other
Project description:The majority of patients with operable esophageal cancers present with locally advanced disease, for which surgical resection as a sole treatment modality has been historically associated with poor survival. Even following radical resection, most of these patients will eventually succumb to their disease due to distant metastasis. For this reason, there has been intense interest in the role of neoadjuvant therapy. Neoadjuvant therapy primarily consists of either chemotherapy, radiation therapy, or a combination of the two. Multiple studies of variable scope, design, and patient characteristics have been conducted to determine whether neoadjuvant therapy is warranted, and-if so-what is the best modality of treatment. Despite nearly three decades of study, decisions regarding neoadjuvant therapy for esophageal cancer remain controversial. Regardless, the available evidence provided by large, prospective studies supports preoperative chemotherapy as opposed to surgery alone. Therefore, in our opinion, there is no longer any question as to whether induction therapy is appropriate for locally advanced esophageal cancer. Less clear, however, is the evidence that the addition of radiation to chemotherapy in the preoperative setting is superior to neoadjuvant chemotherapy alone. Our group generally advocates for neoadjuvant chemotherapy alone followed by radical esophageal resection. The data for adjuvant therapy are soft, and particularly troubling is the high rate of treatment drop out in trials studying adjuvant therapy. Therefore, we strongly prefer neoadjuvant chemotherapy and reserve adjuvant chemotherapy for those rare, highly selected patients-patients with T1 tumors, for example-who do not receive neoadjuvant treatment and are found to have occult nodal disease at the time of surgery.
| S-EPMC5387137 | biostudies-other
Project description:BACKGROUND:Although radical surgery remains the cornerstone of cure in resectable gastric cancer, survival remains poor. Current evidence-based (neo)adjuvant strategies have shown to improve outcome, including perioperative chemotherapy, postoperative chemoradiotherapy and postoperative chemotherapy. However, these regimens suffer from poor patient compliance, particularly in the postoperative phase of treatment. The CRITICS-II trial aims to optimize preoperative treatment by comparing three treatment regimens: (1) chemotherapy, (2) chemotherapy followed by chemoradiotherapy and (3) chemoradiotherapy. METHODS:In this multicentre phase II non-comparative study, patients with clinical stage IB-IIIC (TNM 8th edition) resectable gastric adenocarcinoma are randomised between: (1) 4 cycles of docetaxel+oxaliplatin+capecitabine (DOC), (2) 2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly paclitaxel and carboplatin) or (3) chemoradiotherapy. Primary endpoint is event-free survival, 1 year after randomisation (events are local and/or regional recurrence or progression, distant recurrence, or death from any cause). Secondary endpoints include: toxicity, surgical outcomes, percentage radical (R0) resections, pathological tumour response, disease recurrence, overall survival, and health related quality of life. Exploratory endpoints include translational studies on predictive and prognostic biomarkers. DISCUSSION:The aim of this study is to select the most promising among three preoperative treatment arms in patients with resectable gastric adenocarcinoma. This treatment regimen will subsequently be compared with the standard therapy in a phase III trial. TRIAL REGISTRATION:clinicaltrials.gov NCT02931890 ; registered 13 October 2016. Date of first enrolment: 21 December 2017.
| S-EPMC6131797 | biostudies-literature
Project description:Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.
| S-EPMC4000488 | biostudies-literature
Project description:PurposeNCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2-positive breast cancer.Patients and methodsPatients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS).ResultsComparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis.ConclusionDFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.
| S-EPMC3236650 | biostudies-literature
Project description:Purpose: There is currently a lack of validated predictors for adjuvant chemotherapy efficacy in patients with gastric cancer (GC). Perineural invasion (PNI) is the process of neoplastic invasion of the nerves, accompanied by tumor microenvironment (TME) changes. TME can determine treatment outcome while the impact of PNI on chemotherapy efficacy remains unknown in GC. We investigated the association between PNI and the efficacy of postoperative adjuvant chemotherapy in patients with resected GC. Methods: Patients who underwent radical resection of stage IB-III GC with or without fluoropyrimidine (FU)-based adjuvant chemotherapy were retrospectively selected from two separate patient cohorts. PNI was confirmed with S100 immunohistochemistry (IHC). Tumor hypoxia and activity of selected pathways were quantified by mRNA-based signature scoring based on publicly available data. A hypoxia biomarker, ERO1A, and a FU resistance biomarker, thymidylate synthase (TS), were assessed by IHC, respectively. Results: Two cohorts included 223 and 599 patients, respectively. Adjuvant chemotherapy significantly improved overall survival (OS) and disease-free survival (DFS) in PNI-positive but not in PNI-negative patients, which was not impacted by stages. Multivariate models showed that adjuvant chemotherapy was an independent predictor for OS and DFS in PNI-positive patients in both cohorts. For TME, PNI-negative tumors were more hypoxic than were PNI-positive tumors, and displayed relative up-regulation of signaling along the pathways that are important in FU metabolism or resistance. Expressions of ERO1A and TS significantly decreased in PNI-positive compared to PNI-negative tumors. Conclusions: PNI might help predict adjuvant chemotherapy benefit in patients with resected GC. Validation in prospective studies is required. Novel treatment strategies need to be developed in PNI-negative patients.
| S-EPMC7186485 | biostudies-literature
Project description:Survival from gastric cancer remains poor, particularly in Western populations. Previous pre-clinical and subgroup analyses of clinical trials have suggested differing benefits from fluoropyrimidine-based chemotherapeutics for diffuse and intestinal gastric cancer. This analysis examines patterns of relapse with and without adjuvant chemotherapy after curative resection for gastric cancer in these subtypes to explore the Lauren classification as a predictive marker of benefit for fluoropyrimidine-based adjuvant chemotherapy.Gastric cancer patients enrolled in an ongoing tissue banking study were analysed, 164 patients who would currently be considered for adjuvant therapy after curative resection were included in the analysis. Patients who did and did not receive adjuvant chemotherapy were compared. The primary end point was relapse free survival.Approximately 50% of patients received adjuvant chemotherapy, the majority receiving a fluoropyrimidine-based regimen. The comparison of Kaplan-Meier curves for patients who did and did not receive adjuvant chemotherapy are different between patients with intestinal and diffuse gastric cancer, and suggest that there may be a benefit in intestinal gastric cancer. The hazard ratio for adjuvant chemotherapy for intestinal gastric cancer was 0.56, (95% CI 0.27-1.17), suggesting a trend towards benefit that was lacking in diffuse gastric cancer patients (1.26, 95% CI 0.70-2.38). The patterns of relapse after adjuvant chemotherapy also differed between diffuse and intestinal gastric cancer. More than 50% of diffuse gastric cancer patients who received adjuvant chemotherapy relapsed within 12 months of surgery despite similar surgical parameters.Lauren classification is prognostic in gastric cancer. This analysis adds further evidence that it may also be predictive of benefit for fluoropyrimidine-based chemotherapeutics, with lower chemosensitivity seen in diffuse gastric cancer. Treating diffuse and intestinal gastric cancer as separate entities, with identification of efficacious treatments for diffuse gastric cancer will help in improving outcomes from gastric cancer.
| S-EPMC5602536 | biostudies-literature
Project description:BackgroundThe efficacy and benefits of adjuvant chemotherapy (AC) for patients with gastric cancer pT3N0M0 remain controversial.MethodsWe prospectively collected and retrospectively analyzed 235 patients with pT3N0M0 gastric cancer who underwent radical resection between February 2010 and January 2016. Patients were divided into two groups: the surgery-alone (SA) group (n = 82) and the AC group (n = 153). We analyzed the effects of AC on the overall survival (OS) and recurrence-free survival (RFS), and the relationship between the number of chemotherapy cycles (CC) and recurrence rate (RR).ResultsThe 5-year OS and RFS of the participants were 80.9% and 87.7%, respectively, and those in the AC group were significantly higher than those in the SA group (86.9% vs. 69.5%, p = 0.003). The RFS of the AC and SA groups were 88.9% and 85.4%, respectively; the difference was not statistically significant (p = 0.35). The independent risk factors affecting the OS were perineural invasion-positive (PNI+) (HR = 2.64, 95%CI: 1.45-4.82, p = 0.003) and age ≥ 65 years (HR = 2.58, 95%CI: 1.39-4.8, p = 0.003). The independent risk factor affecting the RFS was also PNI+ (HR3.11; 95%CI: 1.48-6.54, p = 0.003). Stratified analysis revealed that postoperative AC can significantly improve the OS of PNI+ patients (AC group versus SA group: 84.1% vs. 45.5%, p = 0.001) and RFS (86.4% vs. 63.6%, p = 0.017). However, perineural invasion negative (PNI-) patients did not show the same results (p = 0.13 and p = 0.48, respectively). According to the number of CC, divided into CC < 3 groups and CC ≥ 3 groups, the cumulative RR in the CC ≥ 3 group of patients with PNI+ was significantly lower than that of the CC < 3 group (7.4% vs. 28.2%, p = 0.037).ConclusionFor pT3N0M0 gastric cancer patients with PNI+, at least three cycles of postoperative AC can significantly reduce the overall RR. This finding should be verified by using large external sample data.
| S-EPMC8428976 | biostudies-literature