Adjuvant and neoadjuvant approaches in gastric cancer

Despite the recent decline in the incidence of gastric cancer in North America and Western Europe, treatment remains a challenging problem for oncologists. Surgery is the primary modality for managing early-stage disease, but most patients who undergo a curative resection develop locoregional or distant recurrence. Consequently, there has been great interest in evaluating strategies to prevent recurrences and improve overall mortality. This article is a review of data on adjuvant and neoadjuvant treatment approaches for gastric cancer, including radiotherapy, chemotherapy, and chemoradiotherapy. Compared with surgery alone, the North American Intergroup 0116 trial demonstrated a clear survival benefit with the administration of a postoperative regimen of 5-fluorouracil, leucovorin, and external beam radiation therapy, and these findings have made concurrent chemoradiation a standard of care in patients with resected gastric cancer. More recently, the British Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) study found that preoperative and postoperative administration of epirubicin, cisplatin, and 5-fluorouracil significantly improved survival beyond surgery alone. Thus, after decades of negative studies, 2 successful strategies in localized gastric cancer are now available. Ongoing and proposed trials include the current Intergroup study (Cancer and Leukemia Group B 80101), which is assessing the role of a potentially more active postoperative chemoradiation regimen. The proposed MAGIC-B study will examine the role of adding bevacizumab to perioperative chemotherapy, and the planned CRITICS study by the Dutch Gastric Cancer Group will evaluate the role of postoperative chemoradiation in combination with preoperative chemotherapy.     

Adjuvant and neoadjuvant therapy in prostate cancer

While surgery and radiation therapy remain the only definitive treatments for prostate cancer, single modality therapy has been associated with high failure rates in patients with aggressive disease. Although hormonal therapy has been effective in cases of metastatic disease, the timing of treatment with respect to definitive therapy remains controversial. This review will explore the efficacy of hormonal and chemotherapy in both the adjuvant and neoadjuvant settings. A MEDLINE search was performed to identify pertinent articles regarding both adjuvant and neoadjuvant therapy in prostate cancer. Articles of historical relevance in addition to those using large patient numbers with a randomized design were reviewed preferentially. Since hormonal therapy has been considered standard treatment at the time of cancer progression after definitive therapy, many of the randomized trials essentially compared adjuvant therapy to delayed therapy. Historical trials using adjuvant hormonal therapy have been limited due to difficulties in clinical staging, as well as toxicities attributed to the formulations used. More recently, hormonal therapy has been found to delay disease progression, increase disease-free survival, and decrease mortality when given immediately after prostatectomy or radiation therapy in selected patients. Neoadjuvant hormonal therapy can improve disease-free survival and local control when given before radiation therapy; it has only decreased positive surgical margins when given prior to radical prostatectomy. Although hormonal therapy given immediately after either radical prostatectomy or radiation therapy is highly effective, the side effects of persistent long-term use must be weighed for each patient. While the use of chemotherapy has been limited by the lack of active agents, newer combinations have shown effectiveness in patients with hormone refractory disease, raising the possibility of their use in the adjuvant setting.     

胃癌的辅助治疗

辅助化疗可改善日本胃癌患者的生存期;围手术期化疗给欧洲患者带来生存获益;辅助放化疗因其有效性和可行性成为美国胃癌根治术后患者的标准治疗方法;腹腔化疗亦在减少复发转移、延长生存期等方面起到了一定的作用,多在亚洲使用.     

Adjuvant and neoadjuvant therapy for esophageal cancer: a critical reappraisal

Despite important refinements of surgical technique and significant progress in perioperative care, esophageal cancer remains highly lethal. Therefore, hope for improvement in the prognosis of esophageal cancer lies largely in the use of additional therapy. Promising data from numerous Phase II trials and a single Phase III trial led to the widespread adoption of neoadjuvant chemoradiotherapy. However, subsequent randomized trials did not conclusively demonstrate a survival benefit with any of the current neoadjuvant protocols for patients with resectable esophageal cancer. Benefit, if any, exists only for complete pathologic responders. Neoadjuvant chemoradiation should not be used in patients with resectable esophageal cancer outside of the clinical trials. Future investigation must focus on the development of new biologic or chemotherapeutic agents, and the identification of biologic markers that might predict response to chemoradiation.     

Adjuvant and neoadjuvant therapy for early-stage non-small-cell lung cancer

Early-stage non-small-cell lung cancer (NSCLC) carries with it an unfavorable prognosis even in patients who have undergone surgical intervention. Efforts to improve the outcome of patients with early-stage NSCLC have focused on adjuvant or neoadjuvant chemotherapy. The role of adjuvant therapy in NSCLC has been clarified by the recent publication of several large randomized trials. The International Adjuvant Lung Trial was the first prospective trial to report that adjuvant chemotherapy following complete surgical resection of NSCLC improved absolute overall survival by approximately 5% at 5 years. This result has subsequently been confirmed by several other trials. As a result, adjuvant chemotherapy following complete resection of stage IB-III NSCLC can now be considered the standard of care. Neoadjuvant chemotherapy, which has long been investigated for stage III NSCLC, was also recently explored in stage I/II NSCLC. Although neoadjuvant chemotherapy seems promising, more work is needed to comprehensively evaluate and optimize this approach. The current evidence for adjuvant and neoadjuvant therapy in early-stage NSCLC is reviewed in this article.     

Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer

The management of rectal cancer presents substantial challenges. Patients with T3 and/or node-positive rectal cancers are at high risk for local failure and distant metastases (DM). Adjuvant radiation has been shown to decrease local recurrence (LR) rates; however, this local therapy has not been demonstrated to improve survival when compared to surgery alone. In several prospective randomized trials adjuvant chemoradiation with 5-fluorouracil-(5-FU)-based chemotherapy improved LR rates, DM rates, and overall survival (OS). The optimal chemotherapeutic regimen has not been determined; however, studies comparing standard IV bolus 5-FU administration with continuous infusion (CI) 5-FU demonstrated that CI administration was superior. Preoperative therapy has potential advantages over adjuvant therapy such as less acute bowel toxicity and improved sphincter preservation. Preoperative chemoradiation has been shown in several studies to improve LR rates and OS when compared to surgery alone. Our current approach to patients with resectable T3 or N1 cancer in the distal two-thirds of the rectum on preoperative staging is preoperative chemoradiation with planned postoperative chemotherapy. This regimen offers the best chance for local control and disease-free survival while potentially downstaging the tumor and improving sphincter preservation.     

Adjuvant therapy in gastric cancer.

Gastric cancer has a poor prognosis. The majority of patients will relapse after definitive surgery, and 5-year survival after surgery remains poor. The role of adjuvant therapy in gastric cancer has been controversial given the lack of significant survival benefit in many randomized studies so far. The results of a large North American study (Gastrointestinal Cancer Intergroup Trial INT 0116) reported that postoperative chemoradiotherapy conferred a survival advantage compared with surgery alone, which has led to the regimen being adopted as a new standard of care. However, controversies still remain regarding surgical technique, the place of more effective and less toxic chemotherapy regimens, and the use of more modern radiation planning techniques to improve treatment delivery and outcome in the adjuvant and neoadjuvant setting. This article reviews the current status of the adjuvant treatment for gastric cancer including discussion on the research directions aimed at optimizing treatment efficacy. Issues such as the identification of patients who are more likely to benefit from adjuvant therapy are also addressed. Further clinical trials are needed to move towards better consensus and standardization of care.     

Progress in neoadjuvant therapy for gastric cancer

Gastric cancer is one of the most common malignant tumor types in the world and the majority of patients have already reached the advanced stage at the time of initial diagnosis, owing to the subtle symptoms of gastric cancer in the early stage and the low rate of screening in the population. Surgical resection is one of the main treatments for advanced gastric cancer; however, the efficacy of surgery is limited by factors such as low radical resection rate and high distant metastasis rate. A large number of clinical trials have indicated that neoadjuvant therapy (NAT), which consists of neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy and NAT combined with targeted therapy, may improve the therapeutic effect and prognosis of patients to different degrees. However, the benefit of NAT remains controversial due to the heterogeneity of clinical trials and gastric cancer itself. The present review summarizes the main research progress and key breakthrough of NAT for advanced gastric cancer and discusses its prospects.     

Adjuvant and neoadjuvant therapy for primary GIST

Adjuvant therapy for primary GIST has proven benefit in extending disease free survival. Defined risk factors for recurrent disease are based on GIST size, location, and mitotic rate and provide useful guidelines for selecting patients for adjuvant therapy considerations. Neoadjuvant therapy with tyrosine kinase inhibition has potential usefulness in primary GIST, although not yet as standard of care. Advantages can include tumor downsizing to provide opportunity for less morbid surgical resection as well as to decrease risk of intra-op tumor rupture. These theoretical considerations have not been evaluated in large clinical studies.     

Adjuvant and neoadjuvant treatment of breast cancer

Treatment of early breast cancer has been revolutionized during the past 30 years and new data continue to refine our knowledge of systemic treatments for this stage of disease. The updated worldwide overview has confirmed that, in terms of recurrence and survival, the balance of the known long-term benefits and risk favors some months of adjuvant polychemotherapy and/or a few years of tamoxifen for a wide range of patients. Both the overview and individual trials have shown that anthracycline-containing regimens can achieve additional reduction of the risk of disease relapse and death over cyclophosphamide, methotrexate, and fluorouracil (CMF)-like regimens. Paclitaxel-containing regimens appear promising, but require additional confirmation with longer follow-up. By contrast, controversy still exists on the role of high-dose chemotherapy in high-risk patients. Primary (neoadjuvant) chemotherapy is a new modality to treat large operable breast cancers and offers the possibility of breast conservation with treatment results at least similar to those achieved with classical adjuvant regimens. In the near future, newer agents and information gained on the role of prognostic and predictive factors will probably increase the effectiveness of adjuvant and neoadjuvant treatments.     

Adjuvant therapy of breast cancer: Southwest Oncology Group studies

The Southwest Oncology Group has conducted a series of randomized studies of adjuvant therapy in patients with primary breast cancer and positive axillary nodes. The first study, during which combined chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) administered for 1 year was compared with single agent therapy with melphalan (L-PAM) for 2 years, was activated in 1975 and closed in 1978. Of the 366 patients who were eligible, 191 received L-PAM and 175 were given CMFVP. The 2 groups were comparable with regard to known prognostic factors. At a median follow-up of 8 years, CMFVP continues to be superior to L-PAM in disease-free (P = .005) and overall survival (P = .01). Thirty-five percent of patients on CMFVP have died compared with 46% on L-PAM. The greatest survival benefit is apparent in premenopausal women and women with 4 or more positive axillary nodes. Acute toxicity was more frequent with CMFVP than with L-PAM, but it was acceptable and reversible with both regimens. Long-term toxicity was limited to myeloproliferative disease in 2 patients on L-PAM and 1 on CMFVP. The second-generation series of studies, activated in 1979, were designed according to nodal status, estrogen receptor (ER) status, and menopausal status. We randomized ER-negative, node-negative patients to 6 months of combination chemotherapy or to no treatment. Because of slow accrual, the study was closed and patients are now being entered onto a similar intergroup study with the Eastern Cooperative Oncology Group. We randomized ER-negative, node-positive patients to either 1 or 2 years of CMFVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

结直肠癌的辅助和新辅助治疗

结直肠癌正成为我国常见的恶性肿瘤之一,尤其是在大中城市,由于人们生活水平的提高和膳食结构的改变,结直肠癌发病率的上升趋势更加明显。随着医学生物学技术的进展,虽然结直肠癌的手术、放疗和化疗有了长足的进步,但是,仍然有近半数的患者预后很差。影响结直肠癌患者预后的因素较多。主要有:(1)术后TNM分期:文献报道,按美国AJCC临床分期从Ⅰ期到Ⅳ期的患者,其5年生存率则从大于90%降至小于10%[1,2]。(2)病理和临床特性:如分化差、淋巴管受侵、神经受侵、T4的肿瘤、有肠梗阻或肠穿孔、或术前CEA较高等[3,4]。(3)肿瘤的分子特征:如结肠…     

从CLASSIC研究纵观胃癌的辅助治疗

胃癌是世界范围内严重影响人类健康的疾病。手术切除是治疗胃癌的首选,围手术期辅助治疗的应用也日益广泛。本文拟围绕最近报告的胃癌ＣＬＡＳＳＩＣ研究结果,重点对胃癌围手术期治疗的相关研究进行讨论。     

A case of remnant gastric cancer responding to neoadjuvant TS-1 therapy]

We report the case a 77-year-old male with remnant gastric cancer successfully treated with TS-1 as neoadjuvant chemotherapy. His treatment was daily oral administration of 100 mg TS-1 for 28 days. This therapy was safely carried out on an outpatient basis. The histological diagnosis of the resected stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. This case suggests that TS-1 may have a potent therapeutic effect in neoadjuvant chemotherapy for recurrent gastric cancer.     

Adjuvant and neoadjuvant chemotherapy for invasive bladder cancer

Despite technical advances in the surgical or radiotherapeutic treatment of localized invasive bladder cancer, at least 50% of patients ultimately succumb from the growth and progression of microscopic disease beyond the reach of these local treatment modalities. Systemic chemotherapy prior to or immediately following surgery or radiotherapy or concurrently with radiotherapy has been explored in numerous uncontrolled phase II trials and in several randomized phase III trials in an attempt to eradicate this micrometastatic disease burden. Many of these studies have significant flaws in design, implementation, and analysis. All suffer from the lack of highly effective or well-tolerated chemotherapy. These failed attempts and lessons from successful adjuvant chemotherapy trials in other tumor types indicate directions to be pursued in this highly lethal disease.