A novel arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma after vascular supply distribution via superselective embolization

BACKGROUND: Patients with American Joint Committee on Cancer Stage IV advanced pancreatic carcinoma have been treated by systemic chemotherapy, intraarterial chemotherapy, radiation therapy, and multidisciplinary treatment using a combination of these. However, the outcome has not always been satisfactory. In the current study the authors describe the method and results of a new chemotherapy for advanced pancreatic carcinoma. METHODS: To restrict the blood flow into the pancreas (mainly to the great pancreatic artery and the caudal pancreatic artery), the peripancreatic blood vessels were embolized superselectively with microcoils. In 31 patients with advanced pancreatic carcinoma, the catheter tip for the arterial infusion chemotherapy was placed in the splenic artery just proximal to the branching of the great pancreatic artery when the treatment was given for primary tumors, and in the common hepatic artery when the treatment was given for a metastatic liver lesion. The other end of the catheter was connected to an implanted injection port embedded in the femoral region, and 5-fluorouracil and cisplatin were administered by continuous arterial infusion. RESULTS: Of the 31 patients with advanced pancreatic carcinoma, 23 (74%) underwent hemodynamic change and arterial infusion chemotherapy, with a response rate of 73.9% (complete response rate of 8.7% and a partial response rate of 65.2%) and a mean survival period of 18.26 +/- 10.06 months. The 1-year, 2-year, and 3-year survival rates were 90.9%, 42. 8%, and 18.3%, respectively, with a mean survival period of 19.0 months. Of these 23 patients, the 16 patients with liver metastases had a response rate of 68.8% and a mean survival period of 16.25 +/- 8.35 months, whereas the 7 patients without liver metastases had a response rate of 87.5% and a mean survival period of 22.86 +/- 12.69 months. CONCLUSIONS: In patients with Stage IV advanced pancreatic carcinoma, arterial infusion chemotherapy after hemodynamic change was found to be effective against both primary tumors and metastatic liver lesions. The authors believe that the treatment presented in the current study should be attempted, even in patients with advanced pancreatic carcinoma, as long as the blood vessels for vascular supply distribution exist.     

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.     

Advanced pancreatic carcinoma showing a complete response to arterial infusion chemotherapy

We report a patient with advanced carcinoma of the pancreatic body and tail with multiple liver metastases who showed a complete response to hepatic and splenic arterial infusion chemotherapy (HSAIC) with gemcitabine and 5-fluorouracil, following transcatheter peripancreatic arterial embolization (TPPAE) and partial splenic embolization (PSE). Nonresectable advanced pancreatic carcinoma tends to have a low response to medical treatment, with the median survival time being 6 months or less for stage IV cases. We disclose herein that the median survival time of patients receiving HSAIC after TPPAE is more than three times longer than the survival time attained with conventional treatments. However, in patients with advanced carcinoma of the pancreatic tail, for which TTPAE is not applicable, survival times remain low. Thus, in the patient described here, we also performed embolization of the left gastric and short gastric arteries as well as PSE to increase the flow within the great pancreatic and caudal pancreatic arteries via the splenic artery, and gemcitabine and 5-fluorouracil were administered via the splenic artery. As a result of these procedures, marked reduction in the advanced carcinoma of the pancreatic body and tail and of liver metastases was attained.     

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.     

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。     

Hepatic arterial infusion chemotherapy and loco-regional treatment and irradiation of pancreas tumor in non-resectable pancreas cancer with liver metastases

This study seeks to evaluate arterial infusion chemotherapy and radiotherapy for non-resectable pancreatic cancer with liver metastases. Arterial infusion to the liver was performed in 24 patients, 15 of whom received arterial infusion to the pancreas and 9 of whom underwent irradiation for pancreas tumor (40-50 Gy). However, arterial infusion to the liver alone did not prolong survival, but loco-lesional therapy for the pancreas tumor improved quality of life and resulted in good local control. The survival of the two treatment groups (arterial infusion to the liver combined with loco-regional treatment to the pancreas versus systemic chemotherapy) was statistically different (median 7 months versus 3 months, p less than 0.01). Arterial infusion to the pancreas decreased liver metastases as the first site of failure. These results suggested that arterial infusion to both liver and pancreas combined with irradiation for the pancreas tumor are effective in increasing survival time and improving the quality of life.     

Efficacy and problems of hepatic arterial chemotherapy with angiotensin II for liver metastasis from gastric cancer

Hepatic arterial chemotherapy with angiotensin II was performed on 11 patients with liver metastases from gastric cancer. Mitomycin C was injected for 10 minutes via implanted port, whose tip was located in the hepatic artery, when the mean systolic blood pressure rose to 50 percent above the level in the untreated state by intravenous administration of angiotensin II. After this procedure, 5-fluorouracil at 250 mg/day was continuously infused for 5-days. The response could be measured in 6 of all 11 cases (response rate, 55%). CR was found in 3 patients, PR in 3, NC in 1 and PD in 4. The fifty-percent survival period of responders was 362 days, against 239 days in non-responders. Even if the liver metastases completely disappeared, a recurrence could develop in the liver, bone, lung, peritoneum and lymph nodes. We concluded that this mode of chemotherapy effectively controlled liver metastases from gastric cancer, but it was necessary to follow up with second-line therapy for the recurrence of liver and the other organs.     

Biweekly low-dose cisplatin and 5-fluorouracil combination chemotherapy for advanced gastrointestinal carcinoma

Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal, pancreatic or gallbladder adenocarcinoma. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 5-FU 375 mg/m2 was infused for 2 hours as many times as possible. The response rate among patients with gastric cancer was 26%, colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The response rates were not so high, but the median survival time of patients with recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and gallbladder cancer 10.7 months. A patient with unresected advanced pancreatic head cancer with liver and para-aortic lymph node metastases received this therapy 38 times, and lived for 54 months. No severe side effects occurred in any of these cases. Thus, this chemotherapy could well be effective for the outcome of cases of advanced gastrointestinal carcinoma.     

Hepatic arterial infusion chemotherapy with 5-fluorouracil-based regimens in the management of liver metastases of colorectal carcinoma

Background We assessed the efficacy and safety of hepatic arterial infusion chemotherapy, using 5-fluorouracil-based regimens, in the treatment of unresectable liver metastases of colorectal carcinoma. Patients and Methods Thirty patients with liver metastases of colorectal carcinoma were given hepatic arterial infusion chemotherapy using 5-fluorouracil-based regimens, through an implantable port system, inserted into the hepatic artety by percutaneous procedures. Weekly 5-fluorouracil infusions were given to 17 patients, daily 5-fluorouracil infusions were given to 2, the MF (5-fluorouracil-mitomycin) regimen was given to 8, and the FEM (5-fluorouracil-epirubicin-mitomycin) regimen was given to 3. Results The median survival time was 11.6 months, with an overall response rate of 64%. These results were similar to those in previous reports on hepatic arterial infusion chemotherapy using floxuridine. Hematologic and hepatic toxicity was minimal Grade 3 thrombocytopenia occurred in 2 patients (7%), and a grade 2 elevation of alkaline phosphatase, in 1 (4%). Biliary sclerosis was not observed. The major toxicity was nausea and vomiting, grade 2 or 3, most of which was controllable, in 5 patients (18%). The occurrence of hepatic failure resulting in death was significantly (P=0.0015) lower in responsive cases than in nonresponsive cases. Conclusion We consider that 5-fluorouracil-based regimens can be used safely for hepatic arterial infusion chemotherapy with minimal toxicity, and that they are useful in preventing hepatic failure, because of their high response rate.     

Prophylactic hepatic arterial infusion chemotherapy for the prevention of liver metastasis in patients with colon carcinoma: a randomized control trial

BACKGROUND: The liver is the most frequent site of recurrence after curative resection in patients with colon carcinoma. For liver metastasis, a high response rate can be achieved with hepatic arterial infusion (HAI) chemotherapy. In the current study, the authors administered 5-fluorouracil (5-FU) as adjuvant chemotherapy by HAI to patients with colon carcinoma without liver metastases and studied its effects on recurrence in the liver and survival. METHODS: A total of 316 patients with preoperative Stage II or Stage III colon carcinoma (according to the 1997 revision of the International Union Against Cancer TNM staging system) were randomly assigned to receive surgery plus 3-week continuous HAI of 5-FU or surgery alone. There were 305 eligible patients, of whom the 119 patients assigned to the HAI arm actually received 5-FU. The primary endpoint was disease-free survival, whereas the secondary endpoints were overall survival and liver metastasis-free survival. Analysis was by intent to treat. RESULTS: There were no significant differences noted in morbidity between the two treatment arms. During the follow-up period (median, 59.0 months), the incidence of liver metastasis was significantly decreased in the HAI arm whereas there were no significant differences reported between the 2 arms with regard to the frequency of metastasis at other sites. In the HAI arm, the risk ratio for recurrence was 0.40 (95% confidence interval [95% CI], 0.24-0.64; P=0.0002), the risk ratio for death was 0.37 (95% CI, 0.21-0.67; P=0.0009), and the risk ratio for liver metastasis was 0.38 (95% CI, 0.22-0.66; P=0.0005). These differences were found to be significant only for patients with Stage III disease. Toxicities were mild. CONCLUSIONS: A schedule of 3-week HAI of 5-FU given as adjuvant chemotherapy to patients with Stage III colon carcinoma appeared to contribute to a significant decrease in the frequency of liver metastases and was associated with an improved survival rate.     

动脉插管化疗治疗中晚期膀胱肿瘤（附1例报告）

目的 探讨动脉插管化疗对于中晚期膀胱肿瘤的治疗效果。方法 对１１例由于年龄大,体质差,发现较晚,不能耐受麻醉和手术的中晚期膀胱肿瘤患,采用了动脉插管化疗,结果 １１例患治疗后平均存活时间为２６．２±１３．１个月,１年生存率为８１．８％,总有效率为９０．９％,不良反应轻微,结论 动脉插管化疗是目前治疗中晚期膀胱肿瘤的一种较好方法。     

不同化疗途径对中晚期胰腺癌治疗价值的分析

目的评价不同化疗途径对中晚期胰腺癌的治疗价值。方法对15例中晚期胰腺癌患者行单纯静脉化疗,15例行介入动脉化疗,15例行胃十二指肠动脉插管化疗;对患者的临床受益反应、客观疗效、不良反应以及生存期进行分析。结果三组病例的临床受益率分别为25.0%、61.5%和76.5%（P〈0.05）;有效率分别为33.3%、46.2%和64.7%（P〉0.05）;出现严重不良反应的病例分别为4例、2例和1例（P〉0.05）;中位生存时间分别为8.0、9.0和11.5个月（P〈0.05）。结论行胃十二指肠动脉插管化疗可提高中晚期胰腺癌患者的临床受益率,疗效较好,并可延长患者生存期。     

Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3-4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19-45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC.     

Medical treatment of neuroendocrine gut and pancreatic tumors

Surgery has always been considered to be the primary treatment in patients with neuroendocrine gut and pancreatic tumors, but a significant number of patients present liver metastases already at the first visit. There is obviously a need for effective medical treatment and in the present paper we report our experience of treatment with chemotherapy, the somatostatin analogue SMS 201-995 and interferons. In 30 patients with malignant endocrine pancreatic tumors, chemotherapy including streptozotocin plus 5-fluorouracil had an objective response rate of 63% with a mean duration of the objective response of 17.4 months. There was a difference between clinically functioning and nonfunctioning tumors, which had objective response rates of 68% and 50% and mean response duration of 21 and 9.4 months respectively. The new somatostatin analogue SMS 201-995 was used in 10 patients giving an objective response rate of 40% with a mean duration of 13.5 months. In a series of 22 patients treated with human leukocyte interferon, an objective response rate of 77% was obtained with a mean duration of 8.5 months. A combination of streptozotocin plus 5-fluorouracil gave an objective response rate of 10% with a mean duration of 2.7 months among 31 patients with midgut carcinoid tumors. The somatostatin analogue SMS 201-995, tested in 22 patients with carcinoid tumors, gave an objective response rate of 28% with a mean duration of 18.5 months. Interferon has been tried in three separate studies. The first study, including 36 patients with malignant carcinoid tumors treated with human leukocyte interferon, showed an objective response rate of 47% with a mean duration of 34 months. In a randomized controlled study, where human leukocyte interferon was compared with streptozotocin plus 5-fluorouracil including 10 patients in each arm, no objective response was obtained during the six months' observation in the group of patients receiving chemotherapy, whereas 50% responded in the interferon-treated group. In the third study, IFN-alpha 2b or IntronA was tested in 20 patients with malignant carcinoid tumors and gave an objective response rate of 55% during a six-month observation period. With regard to these data chemotherapy and interferons seem to be equally potent in the treatment of malignant endocrine pancreatic tumors, whereas interferons seem to be superior to both chemotherapy and the somatostatin analogue SMS 201-995 in malignant carcinoid tumors. The somatostatin analogue has proved to be particularly useful in the treatment of patients with severe hormone-related clinical symptoms and in the perioperative period.(ABSTRACT TRUNCATED AT 400 WORDS)     

Percutaneous ethanol injection therapy with hepatic arterial infusion chemotherapy for liver metastases from gastric cancer

Ten patients with liver metastases from advanced gastric cancer received percutaneous ethanol injection therapy (PEI) and chemotherapy by hepatic arterial infusion (HAI) via implantable reservoir. A 90% ethanol solution including 10%. Lipiodol was injected in the liver as PEI.5-FU, EPIR and MMC were used as the regimen for HAI chemotherapy. We have performed this therapy (PEI + HAI) for ten patients with liver metastases since February, 1997. These patients have received this therapy for 4-36 months and three patients died within 16 months. However, three patients did not develop any liver failure after this therapy. The median survival rate was 25.2 months. There are statistically significant differences between upto ss and over se of invasion, and between INF alpha and gamma (p = 0.005).     

药盒埋置持续性动脉灌注化疗治疗中晚期胰腺癌的临床研究

 目的　评价药盒埋置持续性动脉灌注化疗治疗中晚期胰腺癌的临床效果。方法　采用左锁骨下动脉药盒埋置持续性动脉灌注化疗治疗的 2 5例胰腺癌患者为介入治疗组 ,同期接受全身化疗的 2 8例胰腺癌患者为全身化疗组 ,两组均给予健择 +5 氟尿嘧啶方案 ,比较两组临床受益反应、肿瘤大小变化、患者生存情况以及毒副反应。结果　介入治疗组和全身化疗组临床受益率分别为 5 2 .0 %和 2 1.4 %(P <0 .0 5 ) ;总有效率 (CR +PR)分别为 16 .0 %和 10 .7% (P >0 .0 5 ) ;中位生存时间分别为 8.1个月和 6 .8个月 (P >0 .0 5 ) ,半年累积生存率分别为 79.4 %和 5 2 .3% (P <0 .0 5 ) ;1年累积生存率分别为 35 .7%和31.5 % (P >0 .0 5 )。毒副反应以胃肠道反应为主 ,无Ⅲ度以上的血液学、胃肠道及肝肾功能的毒副反应。结论　药盒埋置持续性动脉灌注化疗可以提高中晚期胰腺癌的临床受益率和短期生存率     

Hepatic vascular isolation and perfusion for patients with progressive unresectable liver metastases from colorectal carcinoma refractory to previous systemic and regional chemotherapy

BACKGROUND: Many patients with colorectal carcinoma develop unresectable metastases confined to the liver that remain the life-limiting component of disease despite best available systemic or regional chemotherapy. In the current study, the authors present their results using vascular isolation and perfusion of the liver for individuals with progressive, unresectable liver metastases from colorectal carcinoma that were refractory to both previous systemic and regional chemotherapy. METHODS: Seven patients with refractory, progressive, unresectable colorectal carcinoma metastases confined to the liver underwent a 60-minute hyperthermic (39-40 degrees C) isolated hepatic perfusion (IHP) and were followed for toxicity, response, and survival. RESULTS: There was no surgical- or treatment-related mortality; all patients experienced transient Grade 3-4 (according to National Cancer Institute common toxicity criteria) hepatic toxicity. At a median potential follow-up of 16 months, the overall objective radiographic response rate (all partial responses) was 71% (5 of 7 assessable patients). It is interesting to note that two patients who were treated with tumor necrosis factor (TNF) alone demonstrated no response to therapy compared with all five patients who were treated with melphalan and TNF (three patients) or melphalan alone (two patients). For the 5 patients who responded to treatment, the median duration of response was 10 months (range, 10-13 months) and in all 7 patients the mean overall survival was 19.7 months (range, 2-33 months), including 5 months and 7.5 months, respectively, for the 2 patients treated with TNF alone. CONCLUSIONS: The results of the current study demonstrate that IHP using melphalan with or without TNF has significant antitumor activity in this patient population. IHP deserves continued clinical evaluation as a therapeutic modality for patients with unresectable colorectal carcinoma metastases to the liver.     

术中术后放化疗在中晚期胰头癌治疗中的应用

背景与目的：中晚期胰头癌手术切除率低,综合治疗是延长患者生命的手段。本研究旨在探讨术中术后放化疗对中晚期胰头癌的治疗作用,以提高中晚期胰头癌的姑息治疗效果。方法：对27例中晚期胰头癌患者外科施行胆肠吻合术,手术中在放疗科行直线加速器肿瘤区直接照射,同时手术中经胃十二指肠动脉置入埋入式化疗泵,手术后行肿瘤区灌注化疗。随访3—29个月,用直接法计算患者生存率。结果：全疗程结束后肿块均有不同程度缩小,肿瘤直径由术前的平均4．8cm缩小至2．7cm。疼痛缓解率为100％。仍生存者22例,死亡5例,6个月生存率为100％,12个月生存率93．7％,24个月生存率20％,死亡的5例患者平均生存期为17．9个月。结论：内引流加术中放疗和灌注化疗是对中晚期胰头癌患者治疗的可行方法。     

氟脲苷肝动脉持续灌注联合草酸铂静脉化疗治疗肝转移癌

目的观察经肝动脉灌注氟脲苷(FUDR)同时联合草酸铂(OXA)静脉化疗治疗肝转移癌的疗效及毒副反应.方法 28例结直肠癌或胃癌肝转移患者,经肝动脉灌注FUDR,静脉输入OXA治疗2～6个周期.所有病例均行术前术后CT扫描评价治疗效果.随访44个月,评价疗效、生存期及毒副反应.结果总有效率为42.8%,中位生存时间(MST)为25个月,出现肝转移后的MST为15.5个月,1,2,3年生存率分别为89.3%、67.8%和25.0%.结论采用新的化疗方案FUDR加OXA局部联合全身同时化疗安全有效,患者生存期得以延长.     

Outcomes of home anti-cancer chemotherapy--estimation of hepatic arterial infusion chemotherapy for patients with multiple liver metastases

A total of 18 patients (13: colon cancer, 5: gastric cancer) with multiple liver metastases (H3) underwent hepatic arterial infusion chemotherapy (HAI) using an implanted arterial port with portable syringe pumps in our outpatient clinic. Clinical perspective: overall response rate was 22.2% (CR: 1 case, PR: 3 cases (1 case: hepatectomy after HAI), NC: 12 cases, PD: 2 cases), however, 7 of 12 cases of NC were long NC (more than 6 months). No major complications with HAI were experienced. Patient Perspective: After HAI in our outpatient clinic, the 50% survival was 341 days, 50% hospital free days were 319 days and home stay rate was 92.9%. Societal Perspective: cost and hospital stay days were significantly reduced. Home anti-cancer chemotherapy using HAI for gastrointestinal cancer patients with multiple liver metastases was safe and efficient from the viewpoint of medical outcomes.