Adjuvant chemotherapy in gastric carcinoma

The adjuvant chemotherapy (A.C.) is considered as a complementary treatment in patients who underwent radical surgery for gastric cancer, with complete removal of the tumor and absence of macroscopically detectable metastasis. This treatment is generally started within 4-6 weeks after the operation. The indication to A.C. is related practically only to the stage of the disease, due to the fact that no other prognostic factors of an increased risk of relapse have been detected. Two metanalysis have been recently published by Earle (1998) and Floriani (1998); both the two have recognized a possible effective role of the CA for Gastric Cancer. Naturally these "impressions" of efficacy documented by these two metanalysis should be confirmed through new trials with larger recruitment. In these new trials the new generation schedules (weekly PELF, ECF plus 5-FU), which showed an increased response for advanced disease, should be administered.     

Adjuvant chemotherapy in cancer surgery

Isolated surgical approaches to tumor treatment have largely reached a point beyond which prospects appear to be unpromising. The search for more promising therapeutic approaches, therefore, has become a compelling challenge. Surgico-adjuvant tumour chemotherapy has been more thoroughly studied than anything else in that direction. The underlying theoretical concept seems to be persuasive, though clinical results have so far stayed below expectations. Secured prolongation of life, following this therapy, has so far proved to be probable only for cases of osteosarcoma, mammary carcinoma with high risk of recurrence, testicular tumours, and neurogenic tumours. Neo-adjuvant chemotherapy seems to work well in cases of ENT tumours. Model studies into Lewis-Lung carcinoma have shown that therapeutic effects cannot be guaranteed unless a sensitised tumour is treated with an effective preparation. This is likely to add to the long-range importance of the individual aspects relating to surgico-adjuvant tumour chemotherapy. Methods have been and continue to be developed for that purpose. Yet, all of them need to be methodologically improved. At present, waiting for such improvement, surgico-adjuvant tumour chemotherapy should be used only within the framework of controlled clinical studies.     

Adjuvant chemotherapy in colorectal cancer

The current status of adjuvant therapy for colorectal cancer is reviewed using examples from selected, recently completed, randomized, prospective, clinical trials. Although adjuvant systemic therapy is of limited therapeutic efficacy in cancer of the colon, there have been examples of beneficial effects in specific patient subsets. The rationale and current status of adjuvant portal vein hepatic perfusion suggest that it represents a potentially promising approach that must be evaluated in a large prospective randomized study. Finally, the value of adjuvant radiotherapy and chemotherapy for carcinoma of the rectum is assessed. Although one study has demonstrated increased disease-free survival for patients receiving a combination of chemotherapy and radiotherapy, the small numbers in the study preclude any definitive conclusions. The current National Surgical Adjuvant Breast Project, rectal protocol R-01, the largest rectal cancer study with a concomitant "untreated" control, is reviewed and discussed.     

Adjuvant chemotherapy of breast cancer

Many women will not be cured of breast cancer by even the best early detection and surgical techniques because of micrometastases present at diagnosis. Adjuvant therapy has extended the disease-free interval for most patients and lengthens overall survival for many. Combination chemotherapy has become the standard form of adjuvant treatment for premenopausal women with breast cancer and positive lymph nodes after primary therapy. With minimal toxicity, disease-free and overall survival are improved. Results are less impressive or less clear-cut for postmenopausal women or any woman with negative lymph nodes. Long-term toxicities of adjuvant chemotherapy may include second malignancies and cardiac dysfunction. Although these complications probably are rare, they must be considered seriously when weighing chemotherapy for patients in whom its benefits may be slight. Innovations likely to become standard in adjuvant therapy decision making include risk assessment with new prognostic indicators (growth fraction, oncogene expression) and investigation of dose intensification using bone marrow growth factors and autologous stem-cell support.     

Adjuvant chemotherapy for breast cancer

BACKGROUND: Over the past three decades significant advances have been made in the adjuvant treatment of breast cancer. Despite and increasing incidence of breast cancer, mortality has undergone a gradual decline. This decline in mortality is likely due to numerous factors, including earlier stage at diagnosis, advances in local therapy, and advances in systemic treatment of breast cancer. This article review the background and implementation of the current use of chemotherapy in adjuvant setting. METHODS: The authors reviewed data from published randomized trials and meta-analyzes to analyze the rationale behind the current use of systemic chemotherapy in the adjuvant setting. Recent data regarding the use of taxanes as well as neoadjuvant chemotherapy in also presented. CONCLUSION: Numerous randomized trial and the data obtained from the Early Breast Cancer Trialists' Collaborative Group confirm that both pre- and postmenopausal woman benefit from adjuvant chemotherapy. Anthracycline- containing regimens are superior to those hot containing anthracycline, and should be incorporated into the care of most patients with operable breast cancer. The decision to use chemotherapy should be based upon the potential benefits and theoretical risks associated with therapy and individualized for each patient.     

乳腺癌辅助化疗的新概念

乳腺癌辅助化疗始于20世纪50年代后期。最初是在术中应用塞替哌以期消灭肿瘤细胞。此后,微转移概念为延长辅助化疗时间奠定了理论基础。从20世纪70年代的CMF方案到80年代的蒽环类和90年代的紫杉类药物以及近年来生物治疗与化疗的联合应用,从常规用药到密集化疗,乳腺癌的辅助化疗取得了突飞猛进的发展[1,2]。约10多组前瞻性随机临床试验的结果表明,术后辅助化疗可提高存活率、降低复发率和病死率,目前在世界范围内已得到广泛的认同和应用。1个体化辅助治疗(tailoring adjuvant therapy)化疗和内分泌治疗在乳腺癌辅助治疗中亦取得了显著的疗…     

Adjuvant chemotherapy for lung cancer

After analysing 1929 cases of resection for lung cancer under the classification of adjuvant therapy, histology, stage and chronology, we learned positive points of adjuvant chemotherapy and its problems. The five year survival rate of 45 cases of small cell carcinoma is 23.9% (oat cell 18.5%, intermediate 28.6%). Long-term survivors are always found among the stage I patients, however, better results (14.7%-60.6%) have been shown since 1980. This fact must be derived from recent achievements of chemotherapy. Seven cases of adjuvant surgery for small cell carcinoma shows needs of chemotherapy. The randomized controlled study by using vindesine for non-small cell carcinoma, stage III, and also other studies showed no signs of effectiveness of chemotherapy on non-small cell carcinoma. Clinical application of clonogenic cell assay has made an advance in selecting types of chemotherapy. The problems are, however, administration of drugs, i.e. selection of drugs, time and period to administrated, accurate diagnoses and precise judgement of clinical stage and drug tolerance of patients. We expect more effective drugs to come in the near future.     

Adjuvant chemotherapy for breast cancer

Prolonged chemotherapy has been used as an adjuvant to mastectomy in women with involved axillary nodes, in an attempt to ablate or suppress subclinical, micrometastatic disease. The preliminary results and surrounding controversies are reviewed. It is concluded that at this time there is a decreased relapse rate but no increase in survival, and it is in this light that adjuvant chemotherapy cannot be endorsed outside of well-conducted clinical trials.     

Adjuvant treatment of gastric cancer

Adenocarcinoma of the stomach represents a significant problem worldwide. The only known curative treatment of gastric cancer is complete surgical resection of the stomach tumor with surrounding lymph node-bearing areas. However, as many as 50% to 90% of patients undergoing gastric tumor resection relapse and die of cancer. Adjuvant chemotherapy has been used to prevent recurrence of gastric cancer after surgical resection. Single agents including thiotepa and fluorodeoxyuridine have no benefit as adjuvant therapy. Likewise, combination chemotherapy including 5-fluorouracil (5-FU) plus methyl-CCNU, 5-FU plus Adriamycin plus mitomycin C (FAM), and mitomycin C plus 5-FU plus cytosine arabinoside do not result in overall improved survival. Combined modality irradiation plus fluorinated pyrimidine, however, has resulted in long-term survival of patients with known residual gastric cancer. The newest clinical trial in postoperative gastric cancer being performed in the United States will test 5-FU plus leucovorin plus irradiation in a prospectively randomized study in patients with resected stage IB through stage IV stomach cancer. This surgical study, designed with excellent prospective quality control, is actively accruing patients and will be completed in 1.5 to 2.0 years.

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Resumen El adenocarcinoma del estómago representa un problema significativo en todo el mundo. La única forma de tratamiento curativo del cáncer gástrico es la resección del tumor del estómago con las áreas de drenaje linfático. Sin embargo, hasta 50 a 90% de los pacientes sometidos a resección de un tumor gástrico desarrollan recurrencia y mueren por causa de su cáncer. La quimioterapia adyuvante ha sido utilizada para prevenir la recurrencia del cáncer gástrico luego de la resección quirúrgica. Los agentes únicos, incluyendo Thiotepa y FUDR, no han resultado de beneficio como terapia adyuvante. Tampoco la quimioterapia combinada incluyendo 5-FU + Metil-CCNU, 5-FU + Adriamicina + Mitomicina-C (FAM) y Mitomicina-C + 5-FU + Arabinósido de Citosina. Sin embargo, la modalidad combinada de radiación + pirimidina fluorinada ha resultado en sobrevida a largo plazo de pacientes con cáncer gástrico residual reconocido. El ensayo más nuevo en el cáncer gástrico postoperatorio que se realiza en los Estados Unidos somete a prueba el 5-FU + Leucovorín + irradiación en un estudio prospectivo y randomizado en pacientes con cáncer del estómago en los Estados IB a IV. El estudio, diseñado con un excelente control prospectivo de ealidad, actualmente recluta pacientes y estará completo en 1 1/2 a 2 años.

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Résumé L'adénocarcinome de l'estomac est un problème important connu dans le monde entier. La seule chance de guérison de ce cancer reste la résection chirurgicale complète emportant aussi les tissus lymphatiques avoisinants. Cinquante à 90% des patients ayant cu une résection de tumeur gastrique maligne, récidivent, cependant, et décèdent de leur cancer. La chimiothérapie seule, par des produits tels la thiotépa et la FUDR, n'a pas été obtenu les succès attendus. De même, la suvie n'est pas améliorée après les associations de 5 FU et de méthyle CCNU, de 5 FU, de l'adriamycine et la mitomycine-C (FAM) ainsi que de la mitomycine-C, du 5 FU et de la cytosine arabinoide. L'association de la radiothérapie à l'administration de la pyrimidine fluorée améliore la survie à distance des patients ayant un cancer résiduel. L'essai actuellement en cours aux Etats-Unis utilise le 5-FU associé à la vincrystine et à la radiothérapie chez les patients ayant eu une résection gastrique pour cancer des stade 1B à IV. Cette étude chirurgicale marche bien et l'on prévoit qu'elle soit terminée en 1.5 à 2 ans.

     

进展期胃癌病人术后辅助化疗疗效的荟萃分析

目的:评价进展期胃癌病人术后应用辅助化疗的疗效。方法:检索Entrez PubMed数据库、EMBASE数据库、Ovid数据库中的循证医学数据库、ISI Web of Knowledge数据库和中国生物医学文献数据库中有关胃癌术后辅助化疗疗效的随机对照临床试验文献,分析病人术后总生存率的风险比率(hazard ratio,HR)及其95%可信区间(confidence interval,CI)。结果:1998年1月至2009年12月间共检索到13篇文献(4067例病例),Jadad评分均为3分。发现手术合并化疗组相对于单独手术组病人的术后生存率的HR(95%CI)为0.79(0.72,0.86),亚组分析发现术后辅助化疗的有效性不受肿瘤淋巴结转移情况、淋巴结清扫手术类型、人种及化疗药物给药途径等因素的影响。源于日本之临床试验报道的术后生存率明显高于西方国家。结论:术后辅助化疗能使进展期胃癌病人获益。标准的D2淋巴结清扫手术联合术后口服氟尿嘧啶化疗是这类病人的最佳选择之一。     

胃癌术后辅助化疗两药和三药方案的选择

目的观察性研究胃癌术后辅助化疗中的两药方案（氟尿嘧啶联合铂类）与三药方案（在两药基础上联合蒽环类）对患者预后的影响。方法回顾性分析2004-2008年在上海复旦大学附属中山医院接受上述两药或三药方案进行术后辅助化疗的胃癌患者的临床资料和随访资料．随访终点为死亡或最终随访日（2010年4月30日）。结果共计316例接受过胃癌根治性手术且无远处转移的患者术后4-6周开始接受辅助化疗．化疗方案的选择根据主治医师和患者双方的讨论后决定。两药组210例,三药组106例。其中三药组较两药组年龄略轻（51岁比57岁．P〈0．01）,余基线情况两组间差异无统计学意义（P〉0．05）。中位随访时间47个月．两药组中位无进展生存期16个月,3年总体生存率59．6％：三药组则分别为23个月和64．8％,两组差异无统计学意义（P=0．656和P=0．293）。严重不良反应发生率两药组21．9％（46／210）。三药组30．2％（32／106）。两组差异无统计学意义（P=0．107）。结论胃癌术后辅助化疗中的三药联合方案未显示优于两药方案。     

Adjuvant radiotherapy and chemotherapy in breast cancer

Three hundred and twenty-two women with involvement of axillary lymph nodes following surgery for operable breast cancer were randomized to receive either postoperative radiotherapy, chemotherapy (CMF) or radiotherapy followed by chemotherapy. There was an increase in disease free interval in pre- and postmenopausal patients receiving radiotherapy and chemotherapy regardless of the number of nodes involved. However, there was a trend towards an improvement in disease related survival only in those patients with more than three nodes involved.     

Adjuvant mitozantrone chemotherapy in advanced prostate cancer

OBJECTIVE: To assess the role of mitozantrone, active in relapsed prostate cancer, as an adjuvant to hormonal treatment in patients with advanced prostate cancer. PATIENTS AND METHODS: Between October 1990 and May 1995, 96 patients were entered into a stratified, randomized, single-institution study of hormonal therapy with a luteinizing hormone-releasing hormone agonist and flutamide, with or without four cycles of adjuvant mitozantrone. Of these, 93 patients were evaluable and the results were analysed in June 1999. RESULTS: Patients with localized prostate cancer receiving adjuvant chemotherapy had a higher initial objective response rate (95% vs 53%, P = 0.008) and median survival (80 vs 36 months, P = 0.04) than patients who were treated with hormonal therapy alone. There was no advantage to adjuvant chemotherapy in patients with metastatic prostate cancer. There were insignificant advantages to chemotherapy in overall response rates (55% vs 39%, P = 0.3) and PSA responses (82% vs 64%, P = 0.11). There was no difference between the patient groups in time to treatment failure. CONCLUSION: There was a survival advantage in using adjuvant mitozantrone in patients with locally advanced prostate cancer. Although the study comprised relative few patients, the follow-up period was long and the advantage significant. We recommend that the study be extended to include more patients.     

Adjuvant chemotherapy for colorectal cancer.

Colorectal cancer is the second most common cancer in the Western world, and yet the survival after potentially curative excisional surgery has improved little over the last half century. Newer tumour prognostic markers are not superior to conventional Dukes'' staging and there are currently no markers which predict response to chemotherapy. Adjuvant chemotherapy has had a chequered past, but recently a number of important prospective studies have demonstrated its proven benefit in patients with Dukes'' stage C colorectal cancer. However, several issues still require clarification. (1) Do immunomodulators such as levamisole have a significant role in adjuvant chemotherapy? (2) Which patients derive most benefit from adjuvant chemotherapy? (3) Do prognostic markers have a role in predicting these patients? Approximately 30% of patients with Dukes'' stage B cancers die of metastatic disease and the role of adjuvant chemotherapy in patients with these tumours seems worth exploring. Only a large randomised trial can give answers to these important questions. Such a trial would also encourage the widespread introduction of standard methods of surgical and pathological assessment.     

奥沙利铂联合S-1 与XELOX 方案在胃癌术后辅助化疗中的临床效果比较

目的:比较奥沙利铂联合S-1与XELOX(奥沙利铂+卡培他滨)方案在胃癌术后辅助化疗中的临床效果.方法:将81例胃癌术后患者随机分入观察组(n=41)和对照组(n=40),观察组给予奥沙利铂+S-1方案化疗,对照组给予XEOLX方案化疗.结果:观察组与对照组的1,2年无复发生存率(RFS)分别为51.3％,61.5％和25.6％,20.5％;1,2年总生存率分别为64.1％和69.2％,30.8％和25.6％;差异均无统计学意义(P=0.361,0.591;P=0.631,0.615).两组的毒副反应主要表现为骨髓抑制、胃肠道反应、手足综合征、口腔黏膜炎、末梢神经毒性及肝肾功能损伤,其中对照组手足综合征的发生率明显高于观察组(P=0.001);所有毒副反应经对症治疗后均好转.结论:奥沙利铂联合S-1与XELOX方案在胃癌术后辅助化疗中效果相当.     

Adjuvant therapy for advanced gastric cancer

The importance of surgery (gastrectomy plus lymph node dissection) for the treatment of advanced gastric cancer is unquestionable, although there has been a disparity in methods used to achieve local control in Asia and the West. The superiority of D2 dissection has not been confirmed in a large multiinstitutional trial, and the long-term follow-up results of a Dutch trial revealed that the recurrence rate was lower in the D2 group. Thus, the European Society for Medical Oncology and the US National Comprehensive Cancer Network guidelines recommend D2 dissection, leading to a worldwide consensus. Meanwhile, the focus of oncology should be on multimodality treatment for cure, and numerous large, randomized clinical trials have established effective adjuvant treatment. In gastric cancer, different evidence emerged first in the USA, followed by Europe, and Japan/the Republic of Korea to become the standard for each: adjuvant chemoradiation, perioperative adjuvant chemotherapy, and postoperative chemotherapy, respectively. The Japanese standard has become adjuvant S-1 chemotherapy for 1 year after surgery, and the optimal regimen for stage III should be further investigated in consideration of other robust results. Other issues include the role of surgery in local control with regard to adjuvant treatment such as radiation and molecular-targeted treatment to establish a worldwide standard.     

Adjuvant chemotherapy in lymph node positive bladder cancer

ObjectivesLymph node-positive bladder cancer is a systemic disease in the majority of patients. Adjuvant chemotherapy given shortly after surgery, when tumor burden is low, seems reasonable, yet there is no proof that it improves survival. In this retrospective study, we compare the outcomes of patients with microscopic lymph node positive bladder cancer (pN1 or pN2) treated with radical cystectomy followed by adjuvant chemotherapy and those who declined chemotherapy.MethodsSixty-seven patients with lymph node positive bladder cancer (26 pN1 and 41 pN2) who underwent radical cystectomy between April 1995 and April 2005 were reviewed. Combined adjuvant chemotherapy (gemcitabine and cisplatin in most patients) was given to 35 patients (52%), but declined by 32 (48%). The two groups were similar in performance status, postoperative complication rate, and N stage but deferring patients were on average 5 years older and had a more advanced T stage. Study primary endpoint was overall survival (OS).ResultsAdjuvant chemotherapy was well tolerated and 28/35 patients (80%) completed all 4 cycles. Median OS of patients given adjuvant chemotherapy was 48 months compared with 8 months for declining patients (hazard ratio 0.13, 95% CI 0.04–0.4, P < 0.0001). Multivariate age adjusted analysis showed that adjuvant chemotherapy was an independent factor affecting OS (hazard ratio 0.2, P < 0.0001).ConclusionThis study supports the use of adjuvant chemotherapy after radical cystectomy in patients with node positive bladder cancer. Study design and patient imbalances make it impossible to draw definitive conclusions.