A Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable advanced pancreatic cancer after vascular supply distribution via superselective embolization

Background: We previously reported that arterial infusion chemotherapy improvedthe response rate and survival of the patients with pancreaticcancer at advanced stages in an open trial. We conducted a PhaseI trial of arterial infusion chemotherapy with gemcitabine and5-fluorouracil for advanced pancreatic cancer after vascularsupply distribution via superselective embolization. Methods: Patients were treated after arterial embolization for hemodynamicchange to restrict the blood flow into the pancreas (mainlyto the great pancreatic artery and the caudal pancreatic artery).Arterial infusion chemotherapy consisted of gemcitabine in dosesthat were increased from 600 to 1000 mg/m² in subsequent cohortson Day 1 plus continuous infusion of 5-fluorouracil 300 mg/m²/dayon Days 1–5 every 2 weeks. Result: Twelve patients were enrolled. The maximum tolerated dose ofgemcitabine was determined to be Level 3 (1000 mg/m²). Onlyvery mild hematological and non-hematological toxicities werenoted. The overall response rate was 33.3%. The median survivaltime was 22.7 (95% CI; 9.5–24.5) months and the 1- and2-year overall survival rates were 83.3 and 25.0%, respectively. Conclusion: Arterial infusion chemotherapy using 1000 mg/m² gemcitabineon Day 1 and 300 mg/m²/day 5-fluorouracil on Days 1–5every 2 weeks warrants a Phase II study.     

A devised method of hepatic and splenic arterial infusion chemotherapy after transcatheter peripancreatic arterial embolization for patients with advanced pancreatic cancer

We previously reported the clinical efficacy based on hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer after transcatheter peripancreatic arterial embolization (TPPAE). However, this medical treatment pointed out a few problems in which the method had its complexity and a limited use of embolus micro-coil numbers. Then, we tried to improve the method in solving those problems. In order to reduce the embolus micro-coil numbers for TPPAE, we divided the micro-coil into several parts. We also devised the method of HSAIC. We used one catheter with a side hole, so that the catheter was able to supply a therapeutic drug for arterial infusion chemotherapy, both to the common hepatic artery and splenic artery. The effective rate for eleven cases was 72.7%, and there were no significant differences from the cases treated with the conventional method of TPPAE-HSAIC. Therefore, the devised treatment was considered to be an easy and useful method for TPPAE and HSAIC.     

DSA下多支超选择性动脉灌注化疗联合手术治疗中晚期乳腺癌的临床疗效分析

目的:探讨中晚期乳腺癌多支超选择性动脉化疗联合手术治疗的临床应用价值。方法:60例经临床穿刺活检病理明确诊断为乳腺癌的患者,随机分为2组,A组为介入化疗组(30例),采用Seldinger’s方法术前在DSA造影下多支供血动脉分别超选择性插管,靶血管区域化疗栓塞。B组为对照组(30例),采用术前常规外周静脉全身注药新辅助化疗,2组化疗方案均用吡柔比星联合紫杉醇。比较两组的近期、远期疗效,生存率,复发率,疗程、并发症及化疗不良反应。结果:A组完全缓解(CR)6例(20.0%),部分缓解(PR)23例(76.7%),稳定(SD)1例(3.3%),CR+PR 29例(96.7%),平均疗程时间(29.8±3.2)d,A组复发5例16.7%),中位生存期39个月。B组CR 1例(3.3%),PR 22例(73.3%),SD 7例(23.3%),CR+PR23例(76.7%),平均疗程时间(39.9±4.5)d,复发16例(53.3%),中位生存期25个月。A组完全缓解率、部分缓解率及有效率均高于对照B组(P<0.05)。平均疗程低于对照组,复发率降低且生存时间延长。结论:中晚期乳腺癌术前多支供血动脉超选择性插管,靶血管区域化疗栓塞可明显提高疗效,降低临床分期,降低化疗不良反应及并发症,增加手术切除机会,减少术中出血和缩短手术时间,降低复发率。     

巨块型子宫颈癌术前超选择动脉内栓塞化疗26例

目的探讨超选择动脉内灌注化疗加栓塞术前治疗晚期子宫颈癌的临床疗效。方法2004年1月至2008年3月间住院未经治疗的ⅡA～Ⅳ期子宫颈癌患者共26例,术前在数字减影血管造影术监视下,采用Seldinger技术行双侧髂内动脉插管灌注化疗药,卡铂80mg,长春新碱2mg,丝裂霉素16mg,明胶海绵颗粒栓塞肿瘤供血明显的分支。妇科检查结合超声和CT测量化疗前后肿瘤大小,计算肿瘤消退百分比。1个月后行根治性子宫切除术。结果栓塞化疗总有效率为92．3％。结论术前化疗可缩小肿瘤病灶,减少淋巴结转移和亚临床播散,增加了根治性子宫切除的机会,有望提高晚期子宫颈癌患者的生活质量和生存率。     

A new regional arterial infusion chemotherapy for patients with advanced pancreatic cancer

Various arterial infusion chemotherapies have been tried for the purpose of local control of advanced pancreatic carcinoma. However, these treatments were not effective against the primary lesion because of its special anatomical position and the complex hemodynamics, although they were effective against the liver metastases. Therefore, the vascular supply distribution was altered by superselective embolization to control the primary legion in the pancreas, after transcatheter peripancreatic arterial embolization toward the primary site. Furthermore, bilateral (hepatic and splenic) arterial infusion chemotherapy was applied to both the primary site and liver metastasis. As a result, the response rate was 73.9%, with a mean survival period 18.26 +/- 10.06 months. We believe that the current chemotherapy was an effective treatment for unresectable pancreatic cancer since it was possible to treat patients with little harm to their quality of life.     

动脉灌注健择治疗中晚期胰腺癌

目的 评价经动脉灌注健择治疗中晚期胰腺癌的疗效。方法 36例患者共行65次经动脉内灌注健择，药量按800～1200mg／m^2，间隔2～4周给药一次。结果 以疾病相关症状改善(DRSI)作为评价近期疗效依据，其中以疼痛改善最为显著。结论 经动脉内灌注健择是治疗中晚期胰腺癌的有效方法，可改善临床症状，提高生存质量。     

动脉灌注结合全身静脉化疗治疗中晚期胰腺癌的临床观察

目的:观察动脉灌注结合全身静脉化疗治疗中晚期胰腺癌的疗效。方法:对12例中晚期胰腺癌患者选择性给予腹腔干动脉和/或肠系膜上动脉灌注吉西他滨和5-氟尿嘧啶,第8天再给予吉西他滨全身静脉化疗。3周为1个治疗周期,完成两个周期后复查CT评价疗效,观察临床受益反应、有效率、生存期及毒副反应。结果:全组患者临床受益率66.7%,有效率(CR PR)16.7%,中位生存时间6.7个月,6个月及9个月累积生存率分别为59.4%、29.6%。毒副反应多为Ⅰ°～Ⅱ°均能耐受。结论:动脉灌注结合全身静脉化疗治疗中晚期胰腺癌可获得较好的疗效,提高生存质量,毒副反应较小,值得临床推广应用。     

Adjuvant arterial infusion chemotherapy for patients with pancreatic cancer

Although surgery is the only potentially curative treatment for pancreatic cancer, patients undergoing complete resection frequently develop liver metastasis, local recurrence, and peritoneal metastasis. Liver metastasis is a common mode for the progression of pancreatic cancer, and the prognosis of patients in whom it occurs is extremely poor. Between January 2000 and December 2002, 10 patients received adjuvant arterial infusion chemotherapy after resection of pancreatic cancer. Eight of these 10 patients underwent pancreaticoduodenectomy and 2 had distal pancreatectomy. Catheters were placed using Seldinger's technique, with the tip being advanced into the common hepatic artery via the femoral artery. Then, 1,000 mg/body of 5-FU was administered by 24-hour continuous infusion for 6 days per week (days 1-3 and 5-7). Two cycles of chemotherapy were delivered through an angiographic catheter without a reservoir port. During this treatment, no severe systemic or abdominal complications were observed. The 2 groups were well balanced with respect to prognostic factors. The survival rate at 1 year was 77.8% and 41.6% for the adjuvant chemotherapy group and non-adjuvant chemotherapy group, respectively, while the 3-year survival rates were 48.6% and 20.8% (Wilcoxon test, p = 0.0649). The median overall survival rate was superior in the adjuvant chemotherapy group, although the difference was not statistically significant. High-dose 5-FU arterial infusion chemotherapy seems to be a safe, tolerable, and effective regimen for the postoperative recurrence of pancreatic cancer.     

Arterial infusion chemotherapy for patients with advanced pancreatic cancer

Although various therapies have been tried to improve advanced nonresectable pancreatic cancer, a sufficient consensus has not yet been obtained about the treatment. We have performed arterial infusion chemotherapy for pancreatic cancer in order to maintain QOL. The response rate was 17.3%, the mean survival time 282.1+/-204.7 days, median survival time 243.0+/-84.7 days, and many patients were continuously treated on an outpatient basis. It is thus expected that survival time and maintenance of QOL can be extended by self-sustaining arterial infusion chemotherapy.     

Hepatic arterial infusion of chemotherapy for advanced hepatocellular carcinoma

Treatment of advanced hepatocellular carcinoma (HCC) remains a significant problem for clinicians. Sorafenib, the only approved agent, improves survival rate, but is associated with a low tumor response rate. Alternative approaches for the treatment of advanced HCC are urgently needed. Hepatic arterial infusion of chemotherapy (HAIC) is a promising modality for the treatment of advanced HCC. Since its introduction, there have been improvements in implantable pumps, in catheter implantation and in the convenience and safety of HAIC in general. Numerous clinical studies have shown that HAIC provides moderate therapeutic efficacy with substantially favorable toxicity profiles in selected patient groups with advanced HCC. However, the lack of large randomized studies means that HAIC is not yet a well‐established treatment for advanced HCC. We believe there is an urgent need for the further investigation of HAIC for the treatment of advanced HCC.     

A phase II trial of transcatheter arterial infusion chemotherapy with an epirubicin-Lipiodol emulsion for advanced hepatocellular carcinoma refractory to transcatheter arterial embolization

Introduction Transcatheter arterial embolization (TAE) has been recognized as an effective palliative treatment option for advanced hepatocellular carcinoma (HCC). However, no effective alternative treatments for TAE-refractory HCC have yet been established. The aim of this study was to evaluate the antitumor activity and toxicity of transcatheter arterial infusion chemotherapy using an epirubicin-Lipiodol emulsion in patients with TAE-refractory HCC. Methods Patients with TAE-refractory HCC were enrolled. A dose of 60 mg/m² epirubicin emulsified in Lipiodol and contrast medium was administered from the feeding artery of the HCC. Treatment was repeated every 4 to 12 weeks if there was no evidence of tumor progression or unacceptable toxicity. Results Twenty patients were enrolled in this trial. The median number of treatment courses was 1 (range 1–4). Among the enrolled patients, one (5%) achieved a partial response, and three (15%) showed a minor response. Five (25%) patients had no change and 11 (55%) showed progressive disease. The median survival time, 1-year survival rate and median progression-free survival time for the patients as a whole were 12.4 months, 52.6%, and 1.1 months, respectively. The main grade 3 and 4 toxicities were leukocytopenia (35%), neutropenia (65%), thrombocytopenia (30%), and elevations of the aspartate aminotransferase (45%) and alanine aminotransferase (35%) levels. These toxicities were generally brief and reversible. Conclusion Transcatheter arterial infusion chemotherapy with an epirubicin-Lipiodol emulsion appears to have only modest activity with moderate toxicity for treatment of patients with TAE-refractory HCC. These findings do not support its use in practice, and further studies with the same regimen in patients with TAE-refractory HCC are not recommended.     

132例原发性肝癌灌注化疗及栓塞治疗疗效观察

目的 探讨影响肝动脉灌注化疗＋栓塞治疗疗效的因素。方法 １９９３年１月￣１９９７年１０月,对１３２例不能切除的原发性肝癌行选择性插管灌注化疗及栓塞治疗５９７次,肝动脉灌注化疗＋栓塞者１２２例,单纯灌注化疗１０例。结果 １,２,３年生存率分别为８１．８％、３６．４％和１８．２％,疗效较治疗初期有显著提高。肿瘤分期、栓塞剂及其用量、侧支循环的形成以及肝动脉超选择性插管是影响疗效的主要因素。结论 合理施     

Usefulness of C-arm CT during superselective infusion chemotherapy for advanced head and neck carcinoma

Purpose of the study: To evaluate the usefulness of C‐arm computed tomography (CT) during superselective intra‐arterial infusion chemotherapy for advanced head and neck carcinoma. Methods: C‐arm CT was performed during superselective intra‐arterial infusion chemotherapy for 11 patients with advanced head and neck carcinoma located in the hypopharynx (n = 3), maxillary sinus (n = 3), oropharynx (n = 1), larynx (n = 1), extra‐auditory canal (n = 1), tonsil (n = 1) and tongue (n = 1). The usefulness of C‐arm CT during superselective catheterisation was evaluated. Results: On arteriography, nine tumours showed tumour stains and two in the oropharynx or tonsil showed no obvious tumour stains. C‐arm CT was performed one to four times (mean ± standard deviation, 2.5 ± 0.8) in each patient during a single procedure. C‐arm CT clearly showed not only the vascular territory of the selected branch but also the tumour itself in all patients. Intra‐arterial infusion chemotherapy was performed through one to three branches (mean, 1.7 ± 0.9) according to C‐arm CT findings without any complications. Conclusion: C‐arm CT during superselective intra‐arterial infusion chemotherapy was useful to determine the arterial supply of head and neck carcinoma. C‐arm CT may replace conventional CT during superselective arteriography in this procedure.     

Hepatic and splenic arterial infusion chemotherapy after transcatheter peripancreatic arterial embolization for patients with inoperable adenocarcinoma of the pancreas]

Thirty-one patients with advanced pancreatic carcinoma and liver metastases were treated by hepatic and splenic arterial infusion chemotherapy after transcatheter peripancreatic arterial embolization. The response rate for these 31 patients was 61.3%, with a mean survival period of 17.8 +/- 3.2 months and a 50% survival period of 12 months. By site of the primary tumor, the response rate for pancreatic head and body carcinoma was 81%, with a mean survival period of 21.6 +/- 4.0 months and a 50% survival period of 17 months, whereas the response rate for pancreatic caudal carcinoma was 20%, with a mean survival period of 6.1 +/- 0.5 months and a 50% survival period of 6 months. We believe that the current chemotherapy is an effective treatment for advanced pancreatic cancer with liver metastases.     

Continuous transarterial infusion chemotherapy with gemcitabine and 5-Fluorouracil for advanced pancreatic carcinoma

Purpose: Pancreatic carcinoma is one of the most malignant tumors of the alimentary system, with relativelyhigh incidence rates. The purpose of this study was to assess the efficacy and safety of two regimens for advancedpancreatic carcinoma: continuous transarterial infusion versus systemic venous chemotherapy with gemcitabineand 5-fluorouracil. Methods: Of the 48 patients with advanced pancreatic carcinoma receiving chemotherapy withgemcitabine and 5-fluorouracil, 24 received the selective transarterial infusion, and 24 the systemic chemotherapy.For the continuous transarterial infusion group (experimental group), all patients received gemcitabine 1000mg/m2,given by 30-minute transarterial infusion, on day 1 of a 4-week cycle for 2 cycles, and a dose of 600 mg/m2 5-fluorouracil was infused on days 1~5 of a 4-week cycle for 2 cycles. For the systemic venous group (controlgroup), gemcitabine and 5-fluorouracil were infused through a peripheral vein, a dose of 1000 mg/m2 gemcitabinebeing administrated over 30 min on days 1 and 8 of a 4-week cycle for 2 cycles, and a dose of 600 mg/m25-fluorouracil was infused on days 1~5 of a 4-week cycle for 2 cycles. The effectiveness and safety were evaluatedafter 2 cyclesaccording to WHO criteria. Results:The objective effective rate in transarterial group was 33.3%versus 25% in the systemic group, the difference not being significant (P=0.626). Clinical benefit rates(CBR) inthe transarterial and systemic groups were 83.3% and 58.3%, respectively (P=0.014). The means and mediansfor survival time in transarterial group were higher than those of the systemic group (P < 0.005). at the sametime, the adverse effects did not significantly differ between the two groups (P > 0.05). Conclusion: Continuoustransarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate andsurvival time of patients with advanced pancreatic carcinoma, compared with systemic venous chemotherapy.Since adverse effects were limited in the transarterial group, the regimen of continuous transarterial infusionchemotherapy can be used more extensively in clinical practice. A CT and MRI conventional sequence can beused for efficacy evaluation after chemotherapy in pancreatic carcinoma.     

Experience with chemotherapy for advanced pancreatic carcinoma

The effectiveness of different regimens of chemotherapy for advanced pancreatic cancer was compared in 74 cases (1995-1999). 5-fluorouracil (5FU), adriamycin and mitomycin C (FAM) were given to 12 patients, 5FU alone--23, 5FU plus leukovorin--29, and gemcitabine alone--10. Metastases to the liver were detected in 42 (57%) patients. Partial response (40) was registered in: FAM--1 (8%); 5FU--1 (4%); 5FU + leukovorin--3 (10%); gemcitabine--3 (30%). Mean duration (40) was 5.4; 4; 6.1 and 9 months, respectively. Stabilization was recorded in 17 (23%), mean duration--4.4 months; tumor progression--49 (66%). Toxic side-effects of all the regimens were insignificant. Mean survival rates following FAM, 5FU, 5FU + leukovorin were 4.4; 4.2 and 5.6 months, respectively, while that for gemcitabine varied 3-24 months (on average--7.9 months). Survival in patients responsive to chemotherapy was 9.8; remaining patients--4.7 (p (0.05). Chemotherapy for advanced pancreatic carcinoma is a measure of palliation; its use was followed by a 20% increase in survival. Gemcitabine treatment appeared most effective.     

区域动脉灌注治疗进展期胃肠癌的临床观察

目的观察奥沙利铂(L-OHP)联合亚叶酸钙(CF)和5-氟尿嘧啶(5-FU)区域动脉灌注治疗进展期胃肠癌的临床效果及毒副反应。方法对33例进展期胃肠癌无外科手术指征患者,采用Seldinger方法,经皮锁骨下动脉穿刺术,根据肿瘤部位不同(局部复发或远处转移病灶)将导管插入相应主要供血动脉植入药盒,术后经药盒予L-OHP85mg/m2由皮下药盒缓推持续30分钟,CF200mg/m2静滴2小时,5-FU500mg经皮下药盒推入,再予5-FU2.5～3.0g/m2用输液泵持续动脉灌注48小时,以上治疗每两周一次,每28天为一疗程。结果33例随访时间为2～26个月,均可评价疗效。总有效率(CR1例 PR19例)为60.6%,NC8例,PD5例。中位缓解时问为9.8个月。其中3例PR患者经手术或放疗后达CR。主要毒副反应为消化道反应、感觉神经毒性、腹泻等,骨髓抑制轻微。本组患者未见明显肝肾功能损害。结论L-OHP联合CF和5-FU动脉内联合灌注化疗治疗进展期胃肠癌疗效好,毒副反应轻,值得临床研究推广。