Intra-arterial chemotherapy for unresectable pancreatic cancer

Background:A phase II trial of a new intra-arterial chemotherapyregimen for unresectable pancreatic cancer (UPC). Patients and methods:Ninety-six patients with UPC were treatedwith intra-arterial chemotherapy at three-weekly intervals. The schedule usedwas FLEC: 5-fluorouracil 1000 mg/m², folinic acid 100mg/m², carboplatin 300 mg/m²; epirubicin 60mg/m². Results:The overall response rates by CT-scan evaluation were:15% partial response (PR), 44% stable disease (SD), 17%progressive disease (PD). The overall median survival was 9.9 months, and 10.6and 6.8 for UICC stage III and IV, respectively. Pain reduction occurred in42% of patients. A weight gain >7% from baseline occurred in8% of patients. A total of 341 courses of FLEC were administered. Grade3–4 hematological toxicity was seen in 25% of patients;ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; andgrade 3 alopecia in 16%. One sudden death, a pre-infarction angina, anda transitory ischemic attack were observed. The only complication related tothe angiographic procedure was an intimal dissection of the iliac artery. Conclusions:The intra-arterial FLEC regimen was well toleratedand active. It requires only one day of hospitalization. Efficacy could onlybe assessed in a randomized study against a gemcitabine containing regimen.     

动脉灌注新辅助化疗治疗膀胱尿路上皮癌的初步研究

背景与目的:根治性膀胱切除加盆腔区域淋巴结清扫是治疗浸润性膀胱癌的标准术式,但对于非器官局限性膀胱癌,局部复发与远处转移的风险较高。对这部分患者进行以顺铂为基础的新辅助化疗,可以降低复发率,改善手术疗效,提高生存率。本文旨在研究术前动脉灌注化疗对根治术的影响及其对肿瘤的治疗作用。方法:收集2004年至2005年间13例局部浸润性尿路上皮癌患者(T2～T4a),采用吉西他滨与顺铂(gemcitabine andcisplatin,GC)方案给予髂内动脉灌注化疗1～3次,随后8例行膀胱根治性切除术,2例由于肿瘤明显缩小放弃手术治疗,3例行经尿道膀胱肿瘤电切术。评价化疗前后白细胞、红细胞及血小板水平的变化,化疗前后肿瘤大小的变化,以及临床分期与病理分期的的比较。结果:化疗前后白细胞计数之间的差异无显著性(t=0.94,P=0.37),但红细胞及血小板计数之间的差异有显著性(t=3.41,2.38;P=0.00,0.04),但三项绝对计数值均在正常范围之内;化疗前后肿瘤大小的差异有显著性(t=2.52,P=0.04);8例根治性切除术患者中除两例临床分期与病理分期符合外,其余5例均有降期。结论:GC方案新辅助髂内动脉灌注化疗可以缩小肿瘤体积,导致肿瘤降期;化疗前后白细胞无显著降低,化疗导致红细胞及血小板降低,但未对手术造成不良影响。     

Intra-arterial induction high-dose chemotherapy with cisplatin for oral and oropharyngeal cancer: long-term results

Intra-arterial (IA) chemotherapy for curative treatment of head and neck cancer experienced a revival in the last decade. Mainly, it was used in concurrent combination with radiation in organ-preserving settings. The modern method of transfemoral approach for catheterisation, superselective perfusion of the tumour-feeding vessel, and high-dose (150 mg x m(-2)) administration of cisplatin with parallel systemic neutralisation with sodium thiosulphate (9 g x m(-2)) made preoperative usage feasible. The present paper presents the results of a pilot study on a population of 52 patients with resectable stage 1-4 carcinomas of the oral cavity and the oropharynx, who were treated with one cycle of preoperative IA chemotherapy executed as mentioned above and radical surgery. There have been no interventional complications of IA chemotherapy, and acute side effects have been low. One tracheotomy had to be carried out due to swelling. The overall clinical local response has been 69%. There was no interference with surgery, which was carried out 3-4 weeks later. Pathological complete remission was assessed in 25%. The mean observation time was 3 years. A 3-year overall and disease-free survival was 82 and 69%, respectively, and at 5 years 77 and 59%, respectively. Survival results were compared to a treatment-dependent prognosis index for the same population. As a conclusion, it can be stated that IA high-dose chemotherapy with cisplatin and systemic neutralisation in a neoadjuvant setting should be considered a feasible, safe, and effective treatment modality for resectable oral and oropharyngeal cancer. The low toxicity of this local chemotherapy recommends usage especially in stage 1-2 patients. The potential of survival benefit as indicated by the comparison to the prognosis index should be controlled in a randomised study.     

胆囊癌新辅助化疗研究进展

根治性手术依然是目前显著提高胆囊癌患者生存期的最主要治疗措施。胆囊癌起病隐匿的临床特点造成多数胆囊癌患者就诊时已失去手术机会,新辅助化疗充分发挥了化疗药物对肿瘤细胞的作用,使肿瘤达到术前降期目的,从而让一部分原本无法手术切除的肿瘤患者获得手术机会,但有关胆囊癌新辅助化疗的临床试验较少且样本量较小,尚没有大型的Ⅲ期临床试验,因此其临床应用面临着一些障碍。本文通过回顾现有的胆囊癌新辅助化疗临床试验作此综述,介绍相关化疗方式和效果,探讨其潜在的临床应用前景。     

Treatment of esthesioneuroblastoma with chemotherapy: A report of two cases

Esthesioneuroblastoma is an uncommon tumor arising from the olfactory epithelium within the nasopharynx. Conventional treatment consists of surgical resection and irradiation. The use of chemotherapy in limited responses has been reported using cyclophosphamide, thio-TEPA, nitrogen mustard, vincristine, doxorubicin, and chlorambucil as single drugs or in various combinations. Two cases are presented in which neurologic involvement prompted the application of intraventricular methotrexate by an implantable constant infusion drug delivery system in one patient and intra-arterial cis-platinum in combination with intravenous 5-fluorocytosine in a second patient. The tumor of the first patient responded to irradiation followed by methotrexate for four years. The second patient experienced a brief response to the combined chemotherapy following surgery for a recurrent esthesioneuroblastoma. A brief review of the literature regarding chemotherapy and the aggressive form of esthesioneuroblastoma is presented.     

The efficacy and safety of continuous intra-arterial infusion neoadjuvant chemotherapy with surgery for locally advanced gastric cancer: a preliminary pilot study

BackgroundNeoadjuvant chemotherapy (NAC) followed by R0 resection is regarded as a standard treatment strategy for locally advanced gastric cancer (GC); however, the response to systemic chemotherapy remains unsatisfactory. Continuous intra-arterial infusion chemotherapy (CAIC) is a new method, compared with systematic chemotherapy, it can deliver chemotherapy drugs more accurately, so as to achieve higher surgical conversion rate. This study aimed to explore the efficacy and safety of CAIC in locally advanced GC patients.MethodsIn this retrospective pilot study, four patients with histologically confirmed locally advanced GC were identified from a tertiary hospital between May 2018 and December 2018. Clinic stage was belonged to T4N1-3M0 in all cases with potential probability for surgery. All cases received three cycles of NAC by CAIC with oxaliplatin (100 mg on day 1) plus oral S-1 (80 mg/m²/day twice daily for 14 days) (SOX). Contrast-enhanced computed tomography (CT) scans and pathological examinations were performed to evaluate chemotherapeutic response based on the tumor regression grade (TRG) and post-neoadjuvant pathological Tumor Node Metastasis (ypTNM) staging. All cases were regularly followed up with face-to-face interviews at outpatient, abdominal enhanced CT scan and serum tumor markers were be requested at 3-month intervals for up to 1 year postoperatively.ResultsThe obstruction was significantly alleviated after three cycles of CAIC. Contrast-enhanced CT scans showed decreased tumor volume to some extent, along with lymph node shrinkage after treatment. Radical (R0) resection was achieved in all cases. Histopathological analysis showed tumor downstaging in three cases and upstaging in one case. The tumor response to treatment demonstrated TRG1a in one case, TRG1b in one case, and TRG2 in two cases, with an overall tumor regression rate of 100%. No obvious adverse events or perioperative complications were observed during or following treatment. All cases were alive without tumor recurrence or progression after the 1-year postoperative follow-up.ConclusionsOur study may shed light on super-selective CAIC as an effective method for improving the NAC response in locally advanced GC. Future studies with a larger sample sizes and long-term outcomes are required for a final conclusion.     

Superselective intra-arterial chemotherapy with mitomycin C in liver and gallbladder cancer

This phase 2 study was undertaken to evaluate the feasibility and efficiency of superselective intra-arterial chemotherapy with mitomycin C (SIAC) in patients with liver and gallbladder cancer and compare them to hepatic artery ligation (HAL) and regional chemotherapy with 5-fluorouracil (5-FU). Survival time was related to the percent hepatic replacement (PHR) of the tumour (P less than 0.01) in all patients. SIAC had no advantage over HAL +/- 5-FU as chemotherapy regimen for unresectable liver cancer. The overall response rate of SIAC was 42% (15/36), 27% (3/11) for primary liver cancer, 40% (8/20) for hepatic metastases from colorectal cancer and 60% (3/5) for carcinoma of the gallbladder. The patients who responded to SIAC survived significantly longer (P less than 0.005). The survival rate for responders at 1 year was 68% and for non-responders 26%. Chemotherapy toxicity after SIAC occurred in 16 (44%) patients requiring cessation of therapy in 6 (16%) patients. We conclude that the results of this phase 2 clinical trial were not encouraging. There is an urgent need for reliable means of predicting tumour response to chemotherapy and for a more careful patient selection.     

Intra-arterial infusion chemotherapy with mitomycin C containing albumin microspheres

Enhancement of anti-tumor effect by intraarterial embolization chemotherapy with albumin microspheres containing mitomycin C(MMC-ms) was studied. MMC-ms (1.2 mg/kg) was injected into the femoral artery of rabbits and the lower thigh muscle was extirpated to measure the MMC concentration within it. Although the concentration became rapidly decreased in the case of conventional MMC injection, a high MMC level was sustained by MMC-ms injection. In a further study, male Wistar rats weighing 300 to 350 g were injected with MMC-ms into the hepatic artery and then their livers were resected to investigate the process of degradation of MMC-ms. Microspheres were found to be retained in the hepatic arterioles for at least 2 weeks, but in thicker arterioles, fully-packed microspheres were not degraded even over 4 weeks. Clinically, in 22 patients with hepatic malignancies, consisting of 8 primary and 14 metastatic, MMC-ms was injected into the hepatic artery and its antitumor effect was evaluated by CT scan or sonography. Since effective tumor regression was observed in 14 patients (64%) and no serious side effect was seen, the clinical utility and efficacy of intraarterially administered MMC-ms were proved.     

Intra-arterial chemoradiotherapy for locally advanced oral cavity cancer: analysis of therapeutic results in 134 cases

The objective of this study was to investigate the therapeutic results of arterial injection therapy via the superficial temporal artery for 134 cases of stages III and IV (M0) oral cavity cancer retrospectively, and to clarify the prognostic factors. We administered intra-arterial chemoradiotherapy by continuous infusion of carboplatin in 65 cases from January 1993 to July 2002. Systemic chemotherapy was performed on 26 cases at the same time. We administered intra-arterial chemoradiotherapy by cisplatin with sodium thiosulphate in 69 cases from October 2002 to December 2006. Systemic chemotherapy was performed on 48 cases at the same time. The 3-year local control rate was 68.6% (T2-3: 77.9%; T4: 51.3%), and the 3-year survival rate was 53.9% (stage III: 62.9%; stage IV: 45.3%). Regarding the results of multivariate analysis of survival rates, age (<65), selective intra-arterial infusion, and the use of cisplatin as an agent for intra-arterial infusion were significant factors. The therapeutic results of intra-arterial chemoradiotherapy via the superficial temporal artery were not inferior to the results of surgery. In particular, the results of arterial injection therapy by cisplatin with sodium thiosulphate were excellent, so we believe that it will be a new therapy for advanced oral cavity cancer.     

超选择子宫动脉灌注新辅助化疗在局部晚期宫颈癌治疗中的作用

Objective  

The aim of this study was to investigate the role of pre- operative neoadjuvant intra-arterial infusion chemotherapy (NAIC) in treating locally advanced cervical caner.     

保留膀胱手术联合动脉化疗治疗浸润性膀胱癌的临床研究

目的 评价保留膀胱手术联合动脉化疗治疗浸润性膀胱癌的临床疗效.方法 2003年4月～2006年12月,对35例浸润性膀胱癌患者采用经尿道膀胱肿瘤电切或膀胱部分切除术联合GC(吉西他滨 顺铂)方案动脉化疗治疗,总结分析肿瘤控制情况、膀胱保存率和患者的生存率.结果 33例患者获随访,2例失访,平均随访24.3个月(3～45个月).27例无瘤生存,2例带瘤生存,4例死于肿瘤转移,2年生存率为88.8%;19例无复发及转移,5例浅表性复发,3例浸润性复发,6例转移;25例保留膀胱生存,4例行挽救性全膀胱切除,4例死亡,2年膀胱保存率为74.1%.全部患者对动脉化疗耐受良好,无严重全身和局部不良反应.结论 保留膀胱手术联合GC方案动脉化疗治疗浸润性膀胱移行细胞癌近期疗效满意,毒副作用轻,值得临床进一步观察研究.     

动脉灌注榄香烯乳与直肠癌细胞的凋亡和增殖

[目的]探讨术前选择性动脉灌注榄香烯乳对直肠癌细胞凋亡和增殖的影响。[方法]对20例直肠癌患者榄香烯乳灌注前后的肿瘤组织及16例正常直肠粘膜,分别采用TUNEL法及SP法测定细胞凋亡指数（AI）和增殖指数（PI）。[结果]本组患者榄香烯乳灌注前及灌注后7d-10d.AI分别为5.6‰、11.21‰;PI分别为50.05‰、40.16‰,差异均有显著性意义（P<0.01）。[结论]术前选择性动脉灌注榄香烯乳能诱导直肠癌细胞凋亡和抑制其增殖,提示术前灌注榄香烯乳对治疗直肠癌有积极意义。     

Dose intensity of mitomycin C in adjuvant cancer chemotherapy for patients with gastric cancer

Using a cohort of macroscopic curative resections of gastric cancer at stages II, III, and IV, a randomized controlled trial was performed to elucidate the dose efficacy of intensive adjuvant cancer chemotherapy with mitomycin C. Between June 1983 and December 1986, 336 patients with gastric cancer from 31 institutes were enrolled in the study. The cohort was stratified randomly by the telephone method into two arms. Group A received 20 mg and 10 mg of mitomycin C per body intravenously (IV) on postoperative days 0 and 1, respectively, and then tegafur at 600 mg/body daily perorally (PO) from postoperative week 2 for 1 year. Group B also received 0.2 mg of mitomycin C per kg IV at 3, 6, 9, and 12 months after surgery. The background factors in groups A and B were essentially identical, and the adverse effects were tolerable in both groups. The total administered doses of mitomycin C were significantly higher in group B than in group A, according to the protocol. Although no significant differences were observed in the actuarial overall survival rates between groups A and B at stages II, III, and IV, favorable survival was observed in group B, which received histologically absolute curative resection. This dose-intensive adjuvant cancer chemotherapy would be useful for gastric cancer patients treated by histologically curative surgery. © 1994 Wiley-Liss, Inc.     

Low immune index correlates with favorable prognosis but with reduced benefit from chemotherapy in gallbladder cancer

Use of immune index is a new potential approach for cancer classification and prediction. To investigate the status and clinical effect of immune index in gallbladder cancer (GBC), 238 GBC patients from Zhongshan Hospital affiliated to Fudan University were involved in the present study, including 113 patients in a training set and 125 patients in a validation set. Five immune cells (macrophages, neutrophils, regulatory T cells, cytotoxic T cells and mast cells) were selected based on a literature review and the immune index for each patient was calculated using the LASSO regression. A low immune index (<1) was defined as immunotype A and a high immune index (≥1) was defined as immunotype B. The 5‐year overall survival rate for immunotype A was higher than that for immunotype B in the training set and the validation set (70.0% vs 37.0%, P < 0.001; 68.9% vs 47.5%, P = 0.002; respectively). Moreover, the immune index showed higher prediction efficiency compared with all the single immune cells which we selected. When combined with the immune index, the areas under the curve (AUC) of the TNM staging system in both sets were elevated from 0.677 to 0.787 and from 0.631 to 0.694, respectively. Interestingly, gemcitabine‐based chemotherapy only benefits stage II patients of immunotype B and stage III patients of both immunotype A and immunotype B (P = 0.015, P = 0.030, P = 0.011, respectively) but does not work in stage II patients of immunotype A (P = .307). Taken together, the immune index could effectively predict prognosis and the benefits of gemcitabine‐based chemotherapy and might improve on the TNM staging system.     

Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: an old technology in a new era

Aggressive treatment of colorectal cancer (crc) liver metastases can yield long-term survival and cure. Unfortunately, most patients present with technically unresectable metastases; conventional therapy in such patients consists of systemic therapy. Despite advances in the effectiveness of systemic therapy in the first-line setting, the tumour response rate and median survival remain low in the second-line setting. The preferential blood supply from the hepatic artery to crc liver metastases allows for excellent regional delivery of chemotherapy. Here, we review efficacy and safety data for hepatic artery infusion (hai) pump chemotherapy in patients with metastatic crc from the 5-fluorouracil era and from the era of modern chemotherapy.In selected patients with liver-only or liver-dominant disease who have progressed on first-line chemotherapy, hai combined with systemic agents is a viable therapeutic option when performed at experienced centres. Furthermore, significantly improved survival has been demonstrated with adjuvant hai therapy after liver resection in the phase iii setting. The complication rates and local toxicities associated with hai pump therapy are infrequent at experienced centres and can be managed with careful follow-up and early intervention. The major obstacles to the wide adoption of hai therapy include technical expertise for pump insertion and maintenance, and for floxuridine dose modification. The creation of formal preceptor-focused education and training in hai therapy for interdisciplinary medical professionals might encourage the creation and expansion of this liver-directed approach.     

Intra-arterial infusion of mitomycin C in treatment of breast cancer: occurrence of skin necrosis in irradiated patients

Eight previously irradiated breast cancer patients with local recurrences were treated with intra-arterial infusions of 8 mg/m2 mitomycin C given at 3-week intervals. The mean time interval between radiotherapy and intra-arterial chemotherapy was 38 months (range 2-60). In five cases a temporary reduction in tumour size was observed. However, in 3 of the 8 patients severe local pain, starting immediately after the third course of treatment, was followed 4 weeks later by the development of deep necrotic ulcers of the chest wall. These cases are reported here and discussed in relation to the results of previous studies.     

Nonsurgical management of gallbladder cancer: cytotoxic treatment and radiotherapy

Carcinoma of the gallbladder is a rare tumor entity. Apart from surgical intervention, there is no therapeutic measure with curative potential. Therefore, patients with advanced – i.e., unresectable or metastatic – disease present a difficult problem to clinicians, whether to choose a strictly symptomatic treatment or expose the patient to the side effects of potentially ineffective treatment. Despite anecdotal reports about symptomatic palliation and survival advantages, only unrandomized Phase II studies too small to draw meaningful conclusions have been published thus far. Since there is no standard therapy for advanced gallbladder cancer, patients should be offered the opportunity to participate in controlled clinical trials.     

脾多肽对胆囊癌化疗患者细胞免疫功能的影响

目的:探讨脾多肽对接受胆囊癌辅助化疗患者细胞免疫功能的影响。方法:30例胆囊癌辅助化疗患者分为治疗组（化疗+脾多肽）和对照组（单纯化疗）,采用流式细胞术检测淋巴细胞亚群变化。结果:化疗2周期后,治疗组CD4+T、CD8+ T细胞占淋巴细胞总数分别为（53.73±10.24）% 和（18.29±5.81）%,显著高于同期对照组的（31.81±10.19）%和（10.23±5.96）%（P<0.05）。同时,治疗组CD4+T细胞比例较术前的(43.51±7.30)%有明显升高（P<0.05）。治疗组和对照组之间NK细胞比例差别无统计学意义（P>0.05）,两组间化疗毒副作用相似（P>0.05）。结论:脾多肽可提高胆囊辅助化疗患者外周血CD4+T、CD8+ T细胞比例,改善免疫功能。     

术前动脉灌注化疗治疗局部晚期胃癌的系统评价

目的 评价术前动脉灌注化疗与全身静脉化疗或单独手术治疗局部晚期胃癌的有效性和安全性.方法 计算机检索PubMed(2000年1月-2011年5月)、EMBASE(2000年1月-2011年5月),Cochrane Library(2011年第4期),中国生物医学文献数据库(CBM,2000年1月-2011年5月)、中国期刊全文数据库(CJFD,2000年1月～2011年5月)和中文科技期刊全文数据库(CSJD,2000年1月-2011年5月),同时从参考文献中追溯查找.按照纳入标准,全面搜集有关术前动脉灌注化疗(IAIC+S)与全身静脉化疗(IVC+S)或单独手术(S)治疗局部晚期胃癌方面的临床对照试验,无论是否采用随机对照研究.按照Cochrane系统评价方法,由两位研究者独立提取资料和进行质量评价,并用RevMan5.1软件进行统计分析.结果 共纳入7个研究,792例患者.Meta分析结果显示,IAIC+S组与IVC+S组相比,根治性切除率差异有统计学意义,RR(95％ CI)为1.70(1.41～2.05),姑息性切除率差异无统计学意义,RR(95％CI)为0.37(0.04～3.13).在治疗应答率中,病理学应答率、临床应答率RR(95％ CI)分别为1.33(0.96～1.84)和1.32(0.50～3.44).化疗不良反应中,除胃肠反应RR(95％CI)为0.52(0.28～0.94),骨髓抑制、肝功能损害和其他不良反应方面,两组间差异均无统计学意义,RR(95％ CI)分别为0.64(0.38～1.07)、0.88(0.29～2.64)、0.93(0.53～1.61).术后并发症方面,吻合口瘘、腹腔感染和切口感染,两组间差异均无统计学意义,RR(95％CI)分别为2.46(0.49～12.34)、0.53(0.05～5.57)、2.10(0.20～22.26).IAIC+S组与S组相比,根治性切除和姑息性切除率方面两组间差异均存在统计学意义,RR(95％CI)分别为1.30(1.16～1.45)和0.58(0.42～0.79).1、2、3和5年生存率间差异均有统计学意义,RR(95％CI)分别为1.11(1.03～1.20)、1.36(1.09～1.69)、1.70(1.35～2.14)和1.85(1.30～2.65).术后并发症方面,无论吻合口瘘、腹腔感染和切口感染方面两组间差异均无统计学意义,RR(95％CI)分别为0.78(0.27～2.28)、0.65(0.16～2.65)、1.15(0.43～3.10).结论 术前动脉灌注化疗是一种有效且安全的治疗方法.在手术切除率、总生存率、化疗不良反应以及并发症指标上,都显示出动脉灌注化疗的优势.