Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer

Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally advanced gastric cancer (AGC) in the current multidisciplinary treatment model. EORTC trial 40954 has recently reported that NAC plus surgery without postoperative adjuvant chemotherapy could not benefit the locally AGC patients in their overall survival. We performed a meta-analysis of 10 studies including 1518 gastric cancer patients. Stratified subgroups were NAC plus surgery and NAC plus both surgery and adjuvant chemoth...     

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer： Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

AIM:To evaluate the efficacy and toxicity of postopera-tive chemoradiation using FP chemotherapy and oralcapecitabine during radiation for advanced gastric cancerfollowing curative resection.METHODS:Thirty-one patients who had underwent apotentially curative resection for Stage Ⅲ and Ⅳ(MO)gastric cancer were enrolled.Therapy consists of onecycle of FP(continuous infusion of 5-FU 1000 mg/m~2on d 1 to 5 and cisplatin 60 mg/m~2 on d 1)followed by4500 cGy(180 cGy/d)with capecitabine(1650 mg/m~2daily throughout radiotherapy).Four wk after completionof the radiotherapy,patients received three additionalcycles of FP every three wk.The median follow-up dura-tion was 22.2 mo.RESULTS:The 3-year disease free and overall survivalin this study were 82.7% and 83.4%,respectively.Fourpatients(12.9%)showed relapse during follow-up.Eightpatients did not complete all planned adjuvant therapy.Grade 3/4 toxicities included neutropenia in 50.2%,ane-mia in 12.9%,thrombocytopenia in 3.2% and nausea/vomiting in 3.2%.Neither grade 3/4 hand foot syndromenor treatment related febrile neutropenia or death wereobserved.CONCLUSION:These preliminary results suggest thatthis postoperative adjuvant chemoradiation regimen ofFP before and after capecitabine and concurrent radio-therapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized inINT-0116.This treatment modality allowed successfulloco-regional control rate and 3-year overall survival.     

Adjuvant chemotherapy for gastric cancer:Current evidence and future challenges

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.     

胃癌术后辅助治疗的研究进展

辅助化疗能改善亚洲胃癌D2术后患者的生存期。围手术期化疗成为欧洲治疗胃癌的一线治疗方案。美国以术后同步放化疗作为胃癌根治术后的标准治疗模式。因患者基本特征和术式不同,全球难以形成统一的胃癌术后辅助治疗模式。     

Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT o...     

Adjuvant chemotherapy for resected colorectal cancer metastases:literature review and meta-analysis

Surgical resection is the only option of cure for patients with metastatic colorectal cancer(CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence(based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.     

Adjuvant chemotherapy indications for stage I gastric cancer patients with negative lymph node

PurposeWhether adjuvant chemotherapy (AC) has a survival benefit for pathological stage Ⅰ (T1N0 and T2N0) gastric cancer (GC) patients with negative lymph node (N0) remains controversial.MethodsPatients with surgically resected, histologically confirmed pT1N0 and pT2N0 GC between January 2011 and December 2017 at the National Cancer Center, China, were retrospectively reviewed.ResultsA total of 1601 patients who met the inclusion criteria were identified. Independent risk factors for reduced overall survival (OS) identified in the Cox regression analysis were male sex (hazard ratio [HR] 1.454, 95% confidence interval [CI] 1.127–1.876), age ≥ 65 years (HR 1.367; 95% CI 1.071–1.744 ), T2 stage (HR 1.283; 95% CI 1.005?1.638), tumor size > 3 cm (HR 1.704; 95% CI 1.346?2.158), examined lymph nodes (EN) ≤ 15 (HR 1.327; 95% CI 1.058–1.664), and non-signet ring cell carcinoma (Non-SRCC) (HR 1.639; 95% CI 1.123–2.392). While only T2 stage (HR 1.410; 95% CI 1.026?1.936), tumor size > 3 cm (HR 1.755; 95% CI 1.285?2.397), examined lymph nodes (EN) ≤ 15 (HR 1.489; 95% CI 1.101–2.015) were independent risk factors for cause-specific survival (CSS). We divided patients with pT2N0 into four sub-categories according to two significant prognostic factors (size and EN) and found that only patient in group 3 (EN ≤ 15, size >3 cm) with improved CSS benefit from AC (p = 0.049). More significant CSS benefit from AC was identified in Non-SRCC patients within group 3 (p = 0.034).ConclusionAn additional survival benefit related to AC is expected for selected pT2N0 patients. Non-SRCC patients with EN ≤ 15 and tumor size >3 cm may be particularly appropriate candidates for AC.     

Possible adverse effect of failed adjuvant chemotherapy on the prognosis of women receiving consecutive chemotherapy for recurrent breast cancer

Summary This study tried to evaluate the impact of adjuvant chemotherapy on the induction of chemoresistance in radically operated upon breast cancer patients. Remission rate, remission duration and survival of a group of women (n=22) treated with combination chemotherapy (adriamycin and cyclophosphamide, AC) for recurrent breast cancer after failed adjuvant therapy (cyclophosphamide, methotrexate, fluorouracil, vinblastine) were retrospectively compared with the clinical data of non-pre-treated patients (n=28) receiving the same regimen (AC). The two groups of patients were comparable with regard to their risk factors. In the group of women with prior adjuvant chemotherapy only 3 out of 22 had a partial response, lasting 3, 8, and 16 months; the median survival was 50 months. In the group without prior adjuvant therapy 3 complete and 7 partial remissions with a median remission duration of 15.5 months (range 2–54 months) were found; the median survival was 104 months. The percentage of objective responses among the non-pre-treated patients at 36% was almost significantly higher than that of the pretreated women with 14% (p<0.1). Responders to chemotherapy after relapse profited in terms of survival within the first 3 years after radical mastectomy, although no statistically significant difference was observed. The survival data shown assume a shifting of women from a group with better prognosis to a group with unfavourable prognosis following failed adjuvant chemotherapy.     

Treatment of gastric cancer

The authors focused on the current surgical treatment of resectable gastric cancer,and significance of periand post-operative chemo or chemoradiation.Gastric cancer is the 4thmost commonly diagnosed cancer and the second leading cause of cancer death worldwide.Surgery remains the only curative therapy,while perioperative and adjuvant chemotherapy,as well as chemoradiation,can improve outcome of resectable gastric cancer with extended lymph node dissection.More than half of radically resected gastric cancer patients relapse locally or with distant metastases,or receive the diagnosis of gastric cancer when tumor is disseminated;therefore,median survival rarely exceeds12 mo,and 5-years survival is less than 10%.Cisplatin and fluoropyrimidine-based chemotherapy,with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients,is the widely used treatment in stageⅣpatients fit for chemotherapy.Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status     

Efficacy of adjuvant XELOX and FOLFOX6 chemotherapy after D2 dissection for gastric cancer

AIM: To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection. METHODS: Between May 2004 and June 2010, patients in our gastric cancer database who underwent D2 dissection for gastric cancer at the First Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 896 patients were enrolled into this study according to the established inclusion and exclusion criteria. Of these patients, 214 received the XELOX regimen, 48 received FOLFOX6 therapy and 634 patients underwent surgery only without chemotherapy. Overall survival was compared among the three groups using Cox regression and propensity score matchedpair analyses. RESULTS: Patients in the XELOX and FOLFOX6 groups were younger at the time of treatment (median age 55.2 years; 51.2 years vs 58.9 years), had more undifferentiated tumors (70.1%; 70.8% vs 61.4%), and more lymph node metastases (80.8%; 83.3% vs 57.7%), respectively. Overall 5-year survival was 57.3% in the XELOX group which was higher than that (47.5%) in the surgery only group (P = 0.062) and that (34.5%) in the FOLFOX6 group (P = 0.022). Multivariate analysis showed that XELOX therapy was an independent prognostic factor (hazard ratio = 0.564, P < 0.001). After propensity score adjustment, XELOX significantly increased overall 5-year survival compared to surgery only (58.2% vs 44.2%, P = 0.025) but not compared to FOLFOX6 therapy (48.5% vs 42.7%, P = 0.685). The incidence of grade 3/4 adverse reactions was similar between the XELOX and FOLFOX6 groups, and more patients suffered from hand-foot syndrome in the XELOX group (P = 0.018). CONCLUSION: Adjuvant XELOX therapy is associated with better survival in patients after D2 dissection, but does not result in a greater survival benefit compared with FOLFOX6 therapy.     

Neoadjuvant chemotherapy for advanced gastric cancer: a meta-analysis

AIM:To study the value of neoadjuvant chemotherapy (NAC) for advanced gastric cancer by performing a meta-analysis of the published studies.METHODS:All published controlled trials of NAC for advanced gastric cancer vs no therapy before surgery were searched.Studies that included patients with metastases at enrollment were excluded.Databases included Cochrane Library of Clinical Comparative Trials,MEDLINE,Embase,and American Society of Clinical Oncology meeting abstracts from 1978 to 2010.The censor date was...     

Chemotherapy for gastric cancer

Metastatic gastric cancer remains a non-curative disease. Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phaseⅡandⅢstudies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoad-juvant chemotherapy and radiation therapy is discussed. Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considered as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phaseⅢtrials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116 study, postoperative chemoradiation has been accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phaseⅡstudies are showing promising results. PhaseⅢtrials are needed.     

Perioperative chemotherapy for resectable gastric cancer: MAGIC and beyond

Over the last 15 years, there have been major advances in the multimodal treatment of gastric cancer, in large part due to several phase III studies showing the treatment benefits of neoadjuvant and adjuvant chemotherapy and chemoradiation protocols. The objective of this editorial is to review the current high-level evidence supporting the use of chemotherapy, chemoradiation and anti-HER2 agents in both the neoadjuvant and adjuvant settings, as well as to provide a clinical framework for use of this data based on our own institutional protocol for gastric cancer. Major studies reviewed include the SWOG/INT 0116, Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC), CLASSIC, ACTS-GC, Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) and Trastuzumab for Gastric Cancer trials. Although these studies have demonstrated that multiple approaches in terms of the timing and therapy for gastric cancer are effective, no standard of care is widely accepted and questions regarding the optimal timing of chemotherapy, the benefit of radiotherapy, the minimum required extent of lymphadenectomy and optimal chemotherapy regimen still exist. Protocols from the upcoming ARTIST II, CRITICS, TOPGEAR, Neo-AEGIS and MAGIC-B studies are outlined, and results from these studies will provide critical information regarding optimal timing and treatment regimen. Additionally, the future directions of gastric cancer research predicated on molecular profiling and tailored therapies based on targetable genetic alterations in individual patient’s tumors are addressed.     

胃癌腹腔化疗毒副反应的观察和处理

目的 评价胃癌腹腔化疗的毒副反应，并探讨其处理方法。方法 将156例胃癌病人进行随机分组。分为术中即时低渗温热腹腔化疗联合术后早期腹腔化疗组（治疗组），单纯术中即时低渗温热腹腔化疗组（对照组1），未行腹腔化疗组（对照组2），共三组，观察化疗的安全性和毒副反应。结果 治疗组化学性腹膜炎、消化道反应、骨髓抑制和肝功能异常的发生率明显高于两个对照组。结论 应用术中即时，低渗温热腹腔化疗联合术后早期腹腔化疗时化学性腹膜炎的防治不容忽视。     

Cutting-edge evidence of adjuvant treatments for gastric cancer

ABSTRACT

Introduction: In recent decades, adjuvant therapy has secured a firm position in the treatment of gastric cancer by improving patient prognosis. Currently, standard therapy varies between East Asia, Europe and North America due to heterogeneities of the tumor, race, medical environment and/or surgical procedure. Although adjuvant strategies, proved effective in each region and implemented to clinical practice, certain patient populations with advanced gastric cancer show recurrence and a fatal prognosis. The development of a universal adjuvant therapy with a high efficacy and acceptable adverse events or with less toxicity and non-inferiority seems to have become urgent and imperative.

Areas covered: In this review, we aimed to summarize the current knowledge regarding adjuvant therapies for gastric cancer, including chemotherapy, chemoradiotherapy and molecular targeted therapy, based on clinical trials and to introduce the pivotal ongoing phase III trials.

Expert commentary: The efficacy of adjuvant therapy to prevent recurrence remains insufficient although several trials have shown a significant benefit in patients with localized advanced gastric cancer. The development of more effective and universal multimodal adjuvant therapy is required.     

Gastric cancer adjuvant therapy

From a global perspective, gastric cancer is one of the most common and lethal forms of cancer. The incidence of gastric cancer is very high in East Asia and varies considerably in countries of the Western hemisphere. Even after curative resection, the relapse rates are high in stages II and III. Therefore, adjuvant treatment with chemotherapy has been studied with positive results, especially in East Asian populations. In the Western World, where many locally advanced and borderline resectable gastric cancers are diagnosed, perioperative chemotherapy has become a standard of care. Perioperative chemotherapy increases the chances for curative resection. The additional role of radiation therapy, either in the neoadjuvant or in the adjuvant setting, needs to be defined by studies with a quality assurance for all treatment modalities.     

Histological evaluation for chemotherapeutic responses of metastatic lymph nodes in gastric cancer

AIM: To investigate the effect of preoperative chemotherapy (pre-CTx) for metastatic lymph nodes (MLNs) of gastric cancer (GC).METHODS: A retrospective cohort of patients with advanced GC, who underwent pre-CTx followed by gastrectomy, was reviewed. The histological tumor regression grade (TRG), which considered the percentage of residual cancer in the visible tumor bed, was applied to primary tumors and individual MLNs: G1a (complete response), G1b (< 10%), G2 (10%-50%) and G3 (> 50%). The clinical response to pre-CTx was retrospectively evaluated using only MLNs information, and we compared the histological and clinical evaluations of MLNs.RESULTS: Twenty-eight patients were enrolled. A total of 438 MLNs were retrieved, and 22 (5%), 48 (11%), 63 (14%) and 305 (70%) LNs were assigned as G1a, G1b, G2 and G3, respectively. Stratification of the residual MLNs based on the TRGs was as follows: 28 G1b MLNs (9%), 48 G2 MLNs (15%), and 253 G3 MLNs (76%) in the D1 region; 20 (23%), 15 (17%), and 52 (60%) in the D2 region, respectively. However, no significant correlation was found between TRGs in MLNs and clinical response in the subgroup for which evaluation of clinical response was available.CONCLUSION: Pre-CTx does not provide any outstanding histological benefit for MLNs, and an appropriate D2 lymphadenectomy should routinely be performed to offer the chance of curative resection.     

大肠癌和胃癌个体化疗的现状与未来

大肠癌和胃癌是我国常见的肿瘤,由于我国大多数大肠癌和胃癌患者确诊时已属中晚期,因此,化疗作为全身性内科治疗手段成为患者的主要选择.目前肿瘤的"标准化疗"仍然是以大样本统计学结果为基础选择化疗药物的治疗.由于肿瘤本身以及个体之间异质性的存在,同一部位的肿瘤对"标准化疗"的敏感性和毒副作用差异很大.以药物基因组学及药物遗传学为基础的"个体化疗"受到广泛关注,并显示出其潜在的应用前景.本文着重论述大肠癌和胃癌领域"个体化疗"的研究进展,初步探索各种有药物相关基因的应用价值.