进展期胃癌的新辅助化疗

胃癌是最常见的恶性肿瘤之一．在我国胃癌的死亡数占全部恶性肿瘤死亡总数的23,93％。胃癌的治疗是以手术为主的综合治疗。早期胃癌根冶术后5年生存率为90％,但胃癌早期缺乏特异征象。大部分患者（〉70％）就诊时即为Ⅲ、Ⅳ期,尽管可勉强行根治性手术切除,但因亚临床转移灶的存在,易于复发或转移,故总体预后较差。近年来,国内外众多学者对如何改善胃癌患者预后作了大量的探索和研究,新辅助化疗是其中较为有效的方法之一。     

进展期胃癌的新辅助化疗

目前国内临床治疗的胃癌患者大部分属于进展期,早期胃癌患者较少.进展期胃癌手术切除率低,预后差.进展期胃癌行新辅助化疗能使原发肿瘤降期,能提高根治性手术切除率,有改善患者生存率的可能.本文从进展期胃癌新辅助化疗的理论基础、研究现状与进展、效果评估、化疗用药等几个方面对进展期胃癌新辅助化疗进行综述,来说明术前新辅助化疗是进展期胃癌一种有效的治疗手段.     

Neoadjuvant chemotherapy for locally advanced gastric cancer: With or without radiation

The role of perioperative chemotherapy for gastric cancer has been established for gastric cancers in their advanced stage.In most parts of the world,even in Japan and Korea,local recurrence of gastric cancer following curative resection remains a problem.Should radiation be added to chemotherapy to achieve better local and regional control? What is the current evidence? What are the concerns regarding neoadjuvant chemoradiation in terms of safety,efficacy and survival benefit? After a serious review of the literature,the authors conclude that it is still too early to get a definitive answer but radiation seems promising.It may bring a higher pathological response rate.Rationally,more high level clinical trials are needed to confirm the role of radiotherapy in the neoadjuvant setting or to ascertain subsets of patients who may benefit from it.It is of note that surgeons should pay attention to possible complicated circumstances following radiotherapy,maintain proper nutrition status and minimize the occurrence of postoperative complications.As few data are available in Japan and Korea,interpretation and implementation of neoadjuvant radiation or chemoradiation should be done with caution.     

Neoadjuvant chemotherapy for high-grade advanced gastric cancer

Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m², mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 14) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered.

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Resumen Cincuenta y cinco casos de cáncer gástrico avanzado, en los cuales se había confirmado el Estado IV mediante imágenes diagnósticas preoperatorias, recibieron quimioterapia PMVE con el uso combinado de cisplatino (CDDP) 75 mg/m², MMC 10 mg/cuerpo, Ectoposide 150 mg/cuerpo y VHF 400 mg/día. El CDDP y el MMC fueron administrados por vía intravenosa en el primer día, seguidos de Ectoposide 50 mg/día en los días 3, 4 y 5. Todos los pacientes exhibían lesiones medibles, las cuales fueron valoradas por escanografía computadorizada antes y después del tratamiento. Los pacientes fueron ubicados al azar en dos grupos; 29 quedaron en el grupo de la quimioterapia neoadyuvante (QNA) en el cual la quimioterapia PMVE fue practicada preoperatoriamente, y los 26 pacientes restantes fueron sometidos primero a operación y luego a quimioterapia PMVE, constituyendose en el grupo de control. Los antecedentes médicos no eran significativamente diferentes en los dos grupos. La respuesta fue mayor en el grupo de QNA en comparación con el grupo control (62% vs 35%). La tasa de resecabilidad fue de 79% y 88% en el grupo QNA y en el grupo de control, respectivamente. Sin embargo, la rata de casos potencialmente curables fue más alta en el grupo de QNA, en comparación con el grupo control (38% vs 15%). En los casos no resecados, sin embargo, la tasa de sobrevida fue significativamente superior en el grupo de QNA en comparación con el grupo control. Tales resulados pueden significar que en pacientes con cáncer gástrico de alto grado y en estado avanzado se debe considerar primero la quimioterapia como paso inicial (quimioterapia neodyuvante), y luego la cirugía.

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Résumé Cinquante-cinq cas de cancer gastrique avancé, à potentiel très malin (stade IV à l'imagerie préopératoire), ont été traités par une chimiothérapie PMUE comprenant une combinaison de CDDP, 75 mg/m², MMC, 10 mg/Kg poids corporel, d'etopocide, 150 mg/Kg poids corporel et d'UFT, 400 mg/jour. Le CDDP et le MMC ont été donnés par voie intraveineuse à Jl, suivis d'etoposide, 50 mg/jour aux jours 3, 4 et 5. Tous les patients avaient des lésions qui ont pu être évaluées par la tomodensitométrie avant et après le traitement. Ces patients ont été randomisés en deux groupes: 29 ont eu une chimiothérapie néoadjuvante (CNA) par le PMUE en préopératoire, alors que les 26 autres ont d'abord été opérés, et ensuite ont reçu une chimiothérapie PMUE (groupe contrôle). Les caractéristiques des deux groupes ne différaient pas de façon significative. Le taux de réponse était plus haut dans le groupe CNA par rapport au groupe contrôle (62% contre 35%). Le taux de résecabilité était respectivement, de 79 et 88% dans les deux groupes. Le taux de cas potentiellement curables, cependant, était plus élevé dans le groupe CNA par rapport au groupe contrôle (38% contre 15%). Dans les cas de cancer gastrique non réséqués, le pronostic était extrêmement mauvais, quel que soit le groupe. Dans les cancers réséqués, la survie était significativement plus élevée dans le groupe CNA comparé au groupe contrôle. Ces résultats indiquent que chez les patients ayant un cancer gastrique avancé à potentiel très malin, une chimiothérapie néoadjuvante (d'emblée), suivie de chirurgie, peut être le meilleur choix thérapeutique.

     

Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced gastric cancer

We examined the role of neoadjuvant therapy in downstaging locally advanced gastric cancer. Preoperative staging was performed with a combination of CT scans, endoscopic ultrasonography and/or laparoscopy, and laparoscopic ultrasonography. Patients with T ⋝3 tumors and/or node-positive disease by preoperative clinical staging were eligible for entry. Neoadjuvant therapy consisted of two cycles of CPT-11 (75 mg/m²) with cisplatin (25 mg/m²) weekly four times every 6 weeks. This was followed by resection with D2 lymph node dissection and two cycles of intraperitoneal chemotherapy with floxuridine and cisplatin. Twenty-two patients were entered into the study (4 with T3N0 disease and 18 with T3N1 disease). Induction chemotherapy was well tolerated with major toxicities being neutropenia and diarrhea. A median of 78%/75% of the planned dosage of CPT-11/cisplatin was delivered. Two patients withdrew consent during the first cycle and were lost to follow-up. One patient progressed to stage IV disease during induction chemotherapy and did not undergo surgery. Nineteen patients underwent surgery. One patient had undetected stage IV disease (liver) and underwent a palliative R2 resection. Of the 18 remaining patients, 17 had curative R0 resections and one had a palliative R1 resection. A median of 21 lymph nodes (range 1 to 121) were examined histologically. There was one postoperative death. Surgical morbidity did not appear to increase after the neoadjuvant regimen. The median postoperative length of hospital stay was 9 days (range 3 to 75 days). Postoperative pathologic staging yielded 16% T3 lesions compared to 85% before treatment based on clinical staging; postoperative American Joint Committee on Cancer staging yielded 37% stage IIIA disease compared to 70% stage IIIA before treatment. With a median follow-up of 15 months, median survival has not yet been reached. We conclude that CPT-11-based neoadjuvant therapy downstages locally advanced gastric cancer. Further follow-up is necessary to determine the ultimate impact of this combination therapy on recurrence and survival. Presented at the Forty-Second-Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001. Supported in part by Pharmacia Oncology and grants NCI/NIH CA 16087 and GCRC M01RR00096.     

Neoadjuvant chemotherapy for Chinese women with locally advanced breast cancer

Locally advanced breast cancer carries a poor prognosis and is still prevalent in developing countries. The current management usually involves administration of neoadjuvant chemotherapy (NCT). From March 1990 through December 1997, 173 Chinese patients with tumor size greater than 4 cm were treated; 38 received NCT and the other 135 postoperative adjuvant chemotherapy. The regimens for NCT were FEC (5-fluorouracil 600 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 600 mg/m2) for 29 patients and Adriamycin 75 mg/m2 for the rest of the group. Postoperatively the NCT patients received the standard CMF regimen (oral cyclophosphamide 100 mg/m2 for 14 days and intravenous methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 on days one and eight of each cycle). The postoperative adjuvant chemotherapy group received only the CMF regimen. Tumor response after NCT was measured clinically and histologically. The response rate was 75 per cent with 13.2 per cent being complete response. Although there is no difference in response rate the actual reduction in size was greater for patients receiving Adriamycin than FEC (P = 0.001). The only predictive factor of response to NCT was the type of chemotherapy administered. None of the tumor characteristics such as size, nodal status, histological grading, lymphovascular permeation, hormonal receptor status, and c-erb-B2 expression were found to be significant. The overall 5-year probability of survival was 0.44, and there was no difference between groups. The factor important for prognosis was axillary nodal status on histology. The use of NCT did not improve outcome. In summary our results showed that NCT was feasible for Chinese women and good response could be achieved. However, it is the axillary nodal status that determines the final outcome.     

Neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma. Preliminary results

Gastric adenocarcinoma locally advanced or located at the cardia, or of large size or with local lymphadenopathies are of bad prognosis. To improve the surgical results we have tested the feasibility and tumoral efficacity of pre-operative (neoadjuvant) chemotherapy. Twenty patients have been included between 6/87 and 12/88. Median age was 63 years (36-74); all patients were in good general condition (OMS 0-1). The tumors were located at the cardia in 50%. The tumor median size was 10 cm (6-19), pathological lymph nodes were seem at CAT. Scan in 10/20. The neoadjuvant chemotherapy was continuous IV, 5 FU 1 g/m2/day for 5 days + CDDP 100 mg/m2, day 1. The cycles were repeated every 4 weeks. The median number of cycles prior surgery was 2 (1-4) and depended of tolerance and efficacy. We have observed (WHO criteria). 1 CR, 12 PR (Responsible rate: 65%). 6 MR or S. One patient was non evaluable because coronary insufficiency complicating the first cycle. The neoadjuvant chemotherapy toxicity was mainly hematological. The surgical procedure was curative in 15/20 patients; palliative 4 and non feasible for progression 1. Normal rate of post-operative complications was encountered: 2 subphrenic abscess, 1 pneumopathy, 1 stercoral peritonitis. At this date 3/20 patients died (17 patients are still alive, among them 14 are NED (the overall median survival is more than 10 months). This study demonstrated the feasibility and high response rate of neoadjuvant chemotherapy in patients with locally advanced gastric carcinomas. A randomized trial is warranted to demonstrate the survival benefit.     

Neoadjuvant and adjuvant chemotherapy in locally advanced bladder cancer

Radical cystectomy has traditionally been considered the gold standard of treatment for patients with muscle-invasive bladder cancer. Following cystectomy a significant portion of patients will develop systemic relapse, usually within 2 to 3 years. Several randomized trials of neoadjuvant and adjuvant chemotherapy suggest that chemotherapy used in combination with primary treatment may improve disease-free survival and permit bladder preservation in selected cases. Whether or not neoadjuvant and adjuvant chemotherapy influence long-term survival remains controversial. This article reviews in depth the various therapeutic options available to patients with locally invasive bladder cancer.     

局灶进展性胃癌术前与术后行以多西紫杉醇为基础的辅助化疗比较

目的：比较局灶进展性胃癌（LAGC）术前与术后行以多西紫杉醇为基础的辅助化疗的疗效。 方法：将2011年2月—2012年2月间确诊为LAGC的患者72例随机均分为观察组和对照组。观察组行术前化疗，而对照组则行术后化疗。两组治疗后随访12个月，对比两组手术化疗周期、手术切除率、病理学缓解情况，以及两组不良反应和并发症情况和再次手术情况。 结果：两组共行化疗189个周期，其中观察组占比62.43%（118/189），对照组为37.57%（71/189）；观察组化疗1个周期者占4.24%（5/118），对照组为22.54%（16/71），差异均有统计学意义（均P<0.05）。观察组完全反应率为27.78%（10/36），部分反应率为63.89%（23/36），对照组为8.33%（3/36），38.89%（14/36），差异均有统计学意义（均P<0.05）。两组手术切除率及淋巴结清扫情况差异均无统计学意义（均P>0.05）。观察组中不良反应发生率低于对照组（P<0.05），但两组间术后并发症发生率及再次手术情况差异均无统计学意义（均P>0.05）。 结论：LAGC在术前行以多西紫杉醇为基础的辅助化疗可明显改善治疗效果，同时患者耐受性较好，不良反应少。

     

胃癌的新辅助化疗

新辅助化疗 (neoadjuvant chemotherapy,NACT)最早由 Frei提出作为综合治疗的一部分,主要应用于头颈部癌、骨肿瘤、乳腺癌等实体肿瘤,指在恶性肿瘤局部治疗(手术或放疗)前给予的全身性化疗,又称为起始化疗,以示有别于术后辅助化疗.尽管进行了根治性切除,相当一部分局部进展期的胃癌患者仍然会复发;而术后辅助化疗直到最近才被证实可为患者带来微弱的生存益处.     

胃癌的新辅助治疗

现代诊断技术和普查手段已使更多的胃癌病人得以早期发现，但仍有相当部分病人就诊时已属中晚期．且约60％胃癌病人确诊时已存在转移。手术是胃癌病人的首选治疗手段，然而，即使实行“根治”术后，高复发率仍是目前困扰人们的主要问题。大宗荟萃分析结果显示．辅助化疗对改善病人预后、提高其总生存期和无病生存期的疗效仍不尽如人意。近年，新辅助治疗（neoadjuvant therapy，NAT）成为胃癌治疗研究热点之一。     

Neoadjuvant chemotherapy for gastric cancer: Update

Neoadjuvant chemotherapy has recently received increasing attention in an attempt to increase the rate of complete tumor resections, combat systemic metastases, and prolong survival in patients with gastric cancer. The available data indicate that neoadjuvant chemotherapy is feasible and does not increase postoperative morbidity and mortality. Compared to the results that can today be obtained with primary resection and lymphadenectomy, however, preoperative chemotherapy has so far failed to show a clear increase in the rate of complete tumor removal in patients with resectable gastric cancer. In patients with locally advanced or unresectable gastric cancer, preoperative chemotherapy may cause substantial reduction in locoregional tumor mass and thus increase the resection rate. This finding appears to translate into a survival benefit for those who respond to chemotherapy and have subsequent complete tumor resection. Because of severe shortcomings in the study design of the published reports, definite conclusions cannot be drawn from the available studies. Randomized controlled prospective trials are therefore clearly warranted. Exact pretherapeutic tumor staging, standardized resection and lymphadenectomy techniques, diligent evaluation of the resected specimen, and close follow-up are essential when designing these trials to identify subgroups of patients who may benefit from neoadjuvant chemotherapy for gastric carcinoma.

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Resumen En tiempos recientes ha merecido creciente atención la quimioterapia neoadyuvante en un intento por aumentar las tasas de resecciones tumorales completas, combatir metástasis sistémicas y prolongar la supervivencia en pacientes con cáncer gástrico. La información disponible indica que la terapia neoadyuvante es factible y no aumenta la morbilidad ni la mortalidad postoperatorias. En comparación con los resultados que actualmente se obtienen con la resección primaria y la linfadenectomía, la quimioterapia preoperatoria hasta ahora, sin embargo, ha fallado en cuanto a demostrar un claro incremento en la rata de resección completa del tumor en los pacientes con cáncer gástrico resecable. En los pacientes con cáncer gástrico localmente avanzado o no resecable, la quimioterapia preoperatoria puede causar una reducción sustancial de la masa local-regional, y, por lo tanto, un incremento en la tasa de resección. Esto parece traducirse en un beneficio de supervivencia en aquellos pacientes que responden a la quimioterapia y que luego son sometidos a una resección completa de su tumor. Debido a severas limitaciones en el diseño de los informes publicados, no es posible derivar conclusiones definitivas a partir de la información disponible. Por lo tanto, aparece clara la necesidad de realizar ensayos clínicos prospectivos y randomizados. Una muy exacta estadificación tumoral preterapéutica, la resección estandarizada y la técnica de linfadenectomía, el examen meticuloso del espécimen resecado y un cuidadoso seguimiento son esenciales cuando se diseñen ensayos clínicos y se pretenda identificar subgrupos de pacientes que puedan beneficiarse de quimioterapia neoadyuvante para el carcinoma gástrico.

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Résumé On a récemment souligné l'intérêt, chez les patients ayant un cancer gastrique, de la chimiothérapie néoadjuvante pour améliorer le taux de résecabilité complète des tumeurs, pour combattre des métastases systémiques et pour prolonger la survie. En effet, les études disponibles indiquent que la chimiothérapie néoadjuvante est faisable sans augmenter ni la mortalité ni la morbidité. Comparée aux résultats obtenus aujourd'hui par la résection primitive associée à un curage, la chimiothérapie préopératoire, par contre, ne s'est pas montrée capable d'améliorer le taux de résecabilité des tumeurs estimées résécables à priori. Chez le patient ayant un cancer avancé ou non résécable, par contre, la chimiothérapie préopératoire peut réduire considérablement le volume tumoral et augmenter la possibilité de résection. Chez le patient qui répond à la chimiothérapie et qui a, par la suite, une résection complète de la tumeur, la survie apparaît donc améliorée. An raison d'imperfections dans la conception même de certaines de ces études, cependant, il n'est pas possible de tirer des conclusions définitives. Des études contrôlées, et randomisées, sont clairement nécessaires. Un «staging» préthérapeutique exact, une technique de résection et de curage standardisée, une évaluation diligente de la pièce après résection ainsi qu'un suivi rigoureux sont essentiels dans l'élaboration de ces essais pour identifier le sous-groupe de patients ayant un cancer gastrique qui pourraient bénéficier de la chimiothérapie néoadjuvante.

     

Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status

Neoadjuvant therapy followed by breast-conserving surgery has become an acceptable option for patients with locally advanced breast cancer. Although a distinct survival benefit has not been demonstrated using this approach, several questions have been raised following such therapy including its effects on receptor status and tumor markers. The current study retrospectively reviews estrogen receptor (ER), progesterone receptor (PR), and HER2-neu status in 55 consecutive patients treated by neoadjuvant chemotherapy. Preoperative and postoperative tumor markers were available for 43 of the 55 patients (78%). The pathologic complete tumor response rate (pCR) for this group was 19 per cent (8/43). Of those patients who did not achieve a pCR (n = 35), a change in tumor markers was seen in 25.7 per cent (9/35) of patients. When compared to a control group not undergoing neoadjuvant therapy, a significantly higher percent change in marker expression was noted in the neoadjuvant group (25.7% vs 5.9%, P = 0.046). ER, PR, and HER2-neu status remain important prognostic indicators for breast cancer. Tumor markers are useful in planning adjuvant therapy regimens. In this review, nearly 19 per cent of patients achieved a pCR. In patients not achieving a pCR, one in four patients had at least one change in tumor marker status. This study demonstrates the importance of establishing receptor and marker status prior to neoadjuvant therapy, as many patients will achieve a pCR and make tumor analysis impossible. Postoperative marker studies should be performed given the possibility of a change in status. The clinical relevance of this data will require further long-term follow-up. Until such data becomes available, caution should be considered when basing adjuvant therapy regimens on preoperative tumor marker studies alone.     

Intra-arterial chemotherapy for locally advanced bladder cancer

A total of 83 patients with locally advanced bladder cancer (T1, n = 5; T2, n = 28; T3a, n = 21; T3b, n = 21; T4, n = 8) were treated with intra-arterial (i.a.) cisplatin and adriamycin (or epirubicin) chemotherapy. In 51 of the 83 cases, we combined this treatment with radiotherapy. The pathological complete response (CR) rate was 68% for all patients, 84% for i.a. chemotherapy combined with radiotherapy and only 41% for i.a. chemotherapy. The 5-year survival rate was 57% for all patients, 71% for i.a. chemotherapy combined with radiotherapy and only 44% for i.a. chemotherapy. The 5-year survival as a function of the clinical stage was 82% for T1 + T2, 66% for T3a, 28% for T3b, 25% for T4 (T1 + T2 vs: T3b: p < 0.001, T1 + T2 vs. T4: p < 0.0001, T3a vs. T3b: p < 0.0263, T3a vs. T4: p < 0.0214, T3b vs. T4: p < 0.029). In 46% of all patients, we succeeded in preserving the bladder; especially noteworthy, is that in 65% of the patients undergoing i.a. chemotherapy combined with radiotherapy, we succeeded in preserving the bladder. These results demonstrate that i.a. chemotherapy combined with radiotherapy is a useful method for locally advanced bladder cancer which may make preservation of the bladder function feasible.     

Adjuvant chemotherapy for locally advanced bladder cancer

Summary Although controversy over the relative efficacy of full-dose pelvic radiation and radical cystectomy, with or without pre-operative radiation, continues, none of these treatments directed only at the disease in the pelvis cures more than 50 percent of patients with locally advanced disease. An effective systemic therapy is needed. The most effective single agent in metastatic bladder cancer, Cis-platin, has not altered the cure rate when used as an adjuvant. Limited trials using Cis-platin based three and four drug combination chemotherapy regimens have yielded 50–70 percent overall response rates with 30 percent complete responses in metastatic disease. It seems appropriate to perform pilot studies using these more intensive programs as adjuvant chemotherapy for good performance status patients at high risk of progression, e.g. positive lymph nodes.Supported by PHS Grant CA15934 awarded by the National Cancer Institute and the Veterans Administration Medical Research Service     

Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer

Background and aims D₂ gastrectomy has improved survival in gastric cancer. Adjuvant intravenous chemotherapy, radiotherapy, or multimodal therapy has failed to demonstrate improved survival. The results of intraarterial chemotherapy (IARC) as an adjuvant have been encouraging in a few studies. A prospective randomized trial was designed to evaluate the toxicity and survival in locally advanced gastric cancer using IARC as an adjuvant after potentially curative gastrectomy. Patients and methods Forty patients with locally advanced gastric cancer were randomly selected to undergo either potentially curative gastrectomy and receive IARC (study group) or gastrectomy only (control group). Clinical and histopathologic data were analyzed and the toxicity related to IARC was recorded. Results The groups were comparable (p>0.05). Three patients in the study group had minor toxicity. Five-year survival rate for the study and the control group was 52 and 54%, respectively (p>0.05). Mean survival for the study and the control group was 50±8 and 62±10 months, respectively (p>0.05). The number of recurrences and the failure sites were comparable (p>0.05). Conclusion Intraarterial chemotherapy can be safely applied to gastric cancer patients. As proposed by the protocol, the method cannot be recommended as an adjuvant treatment for locally advanced tumors because it appears that there is no survival benefit compared to potentially curative gastrectomy alone.     

以淋巴结转移为主的晚期胃癌的FLEP法新辅助化疗

目的:研究采用经动静脉联合给药的FLEP化疗法,对以淋巴结严重转移为主而不能切除的胃癌进行新辅助化疗,使病人能重新获得手术切除的机会。方法:对14例以淋巴结转移为主的晚期胃癌,以FLEP法进行新辅助化疗。内9例系未经治疗的初诊病人,术前CT检查发现第3、7、9、12组及14、16组淋巴结严重转移,难以手术治疗;5例为术后淋巴结转移性复发,或因淋巴结严重转移而进行过剖腹探查者。FLEP方案为:5-FU 370 mg/m2,iv,第1～5天;Leukovorin 30 mg,第1～5天;CDDP 70 mg/m2与Epotoside 70 mg/m2,ia,第6、20天,每5周重复1次。每一病例视病情进行2～3个疗程的治疗。结果:所有病例症状都明显改善。初次就诊的9例CT评价无变化(NC)1例,未行手术;部分缓解(PR)8例,均进行了胃次全、全胃或联合脏器切除,淋巴结清扫采取了D2加重点淋巴结、D3加第16组淋巴结手术,手术切除率为88.9%,手术治疗的病例均生存至今,最长者已达26个月。在3例术后出现淋巴结转移性复发者及2例因淋巴结严重转移初次手术未能切除者影象学评价PR 3例,病变进展PD 1例,均未再手术治疗。其中2例分别于治疗开始后的8、15个月死亡,另3例至今已生存3～15个月。结论:FLEP新辅助化疗法对于以淋巴结严重转移为主的胃癌具非常显著的治疗效果,可使严重或有远处淋巴结转移的胃癌病人重新获得手术治疗的机会。     

Adjuvant therapy for locally advanced gastric cancer

D2 gastrectomy is now the globally accepted surgical standard for locally advanced gastric cancer. However, since 2000, different evidence has emerged regarding the efficacy of adjuvant chemoradiation, perioperative adjuvant chemotherapy, and postoperative chemotherapy for locally advanced gastric cancer. This review summarizes the background, current status, and future perspectives of adjuvant therapy for locally advanced gastric cancer. The Intergroup 0116 study was the first to show the significant overall survival benefits of adjuvant (chemoradiation) therapy for gastric cancer. The second study was the MAGIC trial, which showed the efficacy of perioperative adjuvant chemotherapy. Although the findings from the Intergroup 0116 study and the MAGIC trial were positive, recent studies, such as the ARTIST and EORTC 40954 studies, found no survival benefit for patients who had undergone D2 gastrectomy for gastric cancer. Regarding the adjuvant chemotherapy strategy, two pivotal phase III trials: the ACTS-GC and the CLASSIC, demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. However, more intensive chemotherapy is necessary to improve the survival rate. Several studies have analyzed the effectiveness of molecular-targeted therapy against metastatic gastric or gastroesophageal junction carcinoma. Further studies should focus on the survival benefit of more-intensive adjuvant therapy with D2 resection, or with concurrent molecular-targeted therapy.