A case of postoperative pelvic metastasis and multiple liver metastases of the rectal cancer successfully treated by arterial infusion therapy with 5-FU/leucovorin

A 55-year-old man underwent a rectal amputation for rectal cancer in 1994. As the tumor marker was elevated in 2002, we performed an abdominal CT scan and detected local and multiple liver recurrences. We treated the patient with intra-arterial infusion of 5-FU/LV via the internal iliac artery and the hepatic artery. The chemotherapy was performed on a weekly basis; it consisted of 5-FU (500 mg/body), administered for 5 hours to bilateral reservoirs through an infusion pump and l-leucovorin (400 mg/body), administered intravenously for 2 hours. After 18 administrations of this regimen during a hospital stay and after a discharge from the hospital as an outpatient, the multiple liver metastases that were observed have disappeared. Further, the local recurrences showed a partial reduction in tumor size with a decrease in perineal pain. Subsequently, the patient did not require further doses of morphine. He exhibited no severe side effects except for grade 1 nausea, and his QOL was also good. Therefore, local intra-arterial infusion chemotherapy with 5-FU/LV appears to have been effective for rectal cancer recurrences.     

A case of local recurrence of rectal cancer responding to local intraarterial infusion therapy]

A 42-year-old male developed pain in the right gluteal region due to local recurrence after curative resection of advanced lower rectal cancer. Radiotherapy (60 Gy) was performed, but satisfactory results were not obtained. Therefore, a reservoir was placed lowing cannulation of the internal iliac artery. The chemotherapy, in addition to intravenous administration of low dose CDDP (20 mg), included local intraarterial infusion therapy with 5-FU (1,500 mg/5 hour) once per week. After 10 courses of this chemotherapy (total dose: CDDP, 200 mg; 5-FU, 15,000 mg), the pain decreased, and the tumor size was reduced without side effects, improving the patient's QOL. At present, multidisciplinary treatments including such chemotherapy and radiotherapy is performed for local recurrence of rectal cancer, but adequate results are often not obtained. Local intraarterial infusion chemotherapy via the internal iliac artery accompanied by changes in blood flow can be safely performed on an outpatient basis, and appears to be effective for local recurrence of rectal cancer.     

Unresectable and locally recurrent rectal cancer treated with radiotherapy or bilateral internal iliac artery infusion of 5-fluorouracil

Seventy-nine patients with histopathologically verified unresectable or locally recurrent rectal cancer were nonrandomly allocated to radiotherapy or regional intra-arterial infusion of 5-Fluorouracil (5-FU). Fifteen patients with unresectable and 32 with locally recurrent rectal cancer were subjected to radiotherapy. The absorbed dose was 30 Gy in patients with an unresectable tumor and 45 Gy in patients with locally recurrent rectal cancer. Six patients with unresectable and 26 with locally recurrent rectal cancer received bilateral internal iliac artery infusion of 5-FU in a median dose of 7.5 g. There was no difference in survival between the two methods of treatment. Resection of an initially unresectable tumor could be performed in 5 of 21 patients (4 after radiotherapy and 1 after chemotherapy). All except eight patients had pelvic or perineal pain before treatment. Forty of 43 (93%) patients reported pain relief after radiotherapy and 21 of 28 (75%) after infusion therapy. Ten nonresponders were subjected to alternative treatment (three to intra-arterial infusion and seven to radiotherapy). Five of these ten patients reported complete pain relief and five partial pain relief. After radiotherapy, no significant side effects or complications were observed. The infusion chemotherapy was the cause of death in one patient. In summary, similar palliation was achieved with bilateral iliac artery 5-FU-infusion and radiotherapy. Owing to the complications registered with infusion therapy, radiotherapy must be considered the treatment of choice for these patients. Patients who do not respond to radiotherapy or suffer recurrence of pelvic and perineal pain may receive further palliation from intra-arterial infusion.     

Five cases of locally advanced rectal cancer or local recurrence performed intra-arterial infusion chemotherapy via the internal iliac artery

Intra-arterial infusion chemotherapy via the internal iliac artery was performed in 5 patients with locally advanced rectal cancer or recurrent rectal cancer. Arterial infusion chemotherapy was conducted into the internal iliac artery via bilateral femoral artery following a blood flow change with a coil. 5 FU 500 mg and l-leucovorin 125 mg/m2 were injected weekly. An average time of injections or its duration was 40 (17-74) times or 12.8 (5-23) months, respectively. Disappearance or improvement of symptoms was observed in 4 cases. A decrease of tumor size observed by CT was in 2 cases and a decrease of blood CEA level was in 3 cases. As for the complication of arterial infusion chemotherapy, dermatopathy was found in all of the cases, and sensory disturbance of lower extremities was in 3 cases, infection was in 2 cases and catheter obstruction was in 2 cases. A decrease of dosage or abundance of continuation was done during the course due to complications. Two patients with primary cancer died 1-3 years after the treatment, and 2 patients with recurrence died 7 months to 1 year after the treatment. One patient with primary cancer is continuing the treatment for the last 2 years though multiple metastatic diseases have been confirmed.     

Intra-arterial infusion chemotherapy in combination with angiotensin II in advanced bladder cancer

Intra-arterial infusion chemotherapy in combination with angiotensin II was performed in 5 patients with advanced bladder cancer (all T3M0). The infusion catheter was inserted from a femoral artery into the internal iliac artery. The basic dosage was 70 mg/m2 of Cis-diammine-dichloroplatinum (CDDP) and 40 mg/m2 of Adriamycin (ADM) or 4'-0-tetrahydropyranyl-ADM (THP) in combination with 20-40 micrograms angiotensin II over a total duration of 20 minutes for both sides. Of the 5 patients, 3 CR and 2 PR were obtained by only one or two courses of intra-arterial infusion chemotherapy. Histological examination showed no viable cells in the three CR cases. Intra-arterial infusion chemotherapy in combination with angiotensin II may thus be clinically useful for advanced bladder cancer.     

卵巢癌术后复发介入化疗疗效分析(附18例临床报告)

目的：总结１８例卵巢癌术后复发患者经介入动脉插管化疗的疗效，并对栓塞剂的应用进行了初步探讨。材料和方法：采用经皮股动脉穿刺双侧髂内动脉选择性插管的方法进行化疗灌注和栓塞。化疗方案为卡铂＋表阿霉素（简称：ＣＡ方案），３例在ＣＡ方案的基础上加用足叶乙甙（ＶＰ－１６），５例同时进行髂内动脉栓塞，所用栓塞材料包括明胶海绵碎块（２例）、顺铂微球（２例）、碘化油（１例）。结果：在１５例可评价疗效的病例中，ＣＲ１例，ＰＲ６例，ＭＲ５例，ＳＤ２例，ＰＤ１例，有效率ＣＲ＋ＰＲ为４６．６％（７／１５）。结论：动脉插管化疗是卵巢癌术后复发较合理的辅助疗法；卡铂＋表阿霉素化疗方案对卵巢癌术后复发有较好疗效；进行髂内动脉栓塞化疗时选用明胶海绵碎块作栓塞剂，副作用较少。     

A case of locally extended rectal carcinoma quickly responding to local intraarterial infusion therapy

Chemotherapy combined with 5-FU and l-leucovorin has been reported to elicit a quick response in cases of lower rectal carcinoma. A 65-year-old woman developed pain in the right gluteal region due to locally extended rectal carcinoma, and was treated with intraarterial infusion therapy. The chemotherapy regimen was 5-FU (500 mg/body) and l-leucovorin (175 mg/body) administered over 3 hours once weekly to bilateral reservoirs through an infuser pump. After 2 sessions of the chemotherapy, the gluteal pain decreased, and after 3 sessions, CEA level was confirmed and the patient's QOL began to improve. Side effects of the intraarterial infusion chemotherapy were gluteal dermatitis, leg desensitization, and infection of the circumferential reservoir. Local intraarterial infusion chemotherapy can be safely performed on an outpatient basis, and appears to elicit quick response for locally extended advanced rectal carcinoma.     

A case of recurrent rectal cancer responding to weekly low-dose CPT-11/isovorin/5-fluorouracil

We report the case of 66-year-old male with recurrent rectal cancer which responded to chemotherapy using CPT-11, Isovorin, and 5-fluorouracil (5-FU). CPT-11 was administered at 40 mg (90 min i.v.) x 3 day/week, and Isovorin and 5-FU were administered at 25 mg (bolus) and 250 mg (continuous) x 5 day/week by intraarterial infusion. Three cycles of this weekly regimen resulted in regression of tumors in the iliac region with remission of the lameness caused by iliac pain. The serum CEA level decreased from 13.1 ng/ml to 0.5 ng/ml. The patient has undergone 13 cycles of the regimen modified for outpatients (CPT-11 at 40 mg x 3 day/week plus Isovorin at 25 mg and 5-FU at 250 mg 1 day/week) with inhibitions of tumor regrowth and improved serum CEA level for more than 12 months. The current case suggests that weekly low-dose CPT-11/Isovorin/5-FU may have a potent therapeutic effect against recurrent rectal cancer.     

Successfully treated locally advanced breast cancer by intra-arterial infusion chemotherapy: a case report]

A 40-year-old female was admitted to our hospital with a large right breast tumor that was over 15 cm in diameter. We treated this locally advanced breast cancer by intra-arterial infusion chemotherapy. Through a catheter placed in the right subclavian artery, doses of 20-30 mg of ADM were injected intermittently with MMC and 5-FU. When a total of 120 mg of ADM had been infused, leukopenia developed, but this was immediately improved by G-CSF. With this treatment, her breast tumor and lung metastases were almost completely disappeared. Thus, an intra-arterial infusion chemotherapy was considered to be an effective treatment for locally advanced breast cancer.     

Evaluation of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer

We evaluated the effect of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer. We performed an intra-arterial infusion chemotherapy (5-FU was injected continuously: 250 mg/day/body x 28 days, CDDP was injected weekly: 5 mg/day x 5 days) associated with radiotherapy (2-3 Gy/day x 20-30 days) for local recurrence of rectal cancer with the aim of pain-relief. Both patients markedly tended to feel less pain after the radiotherapy. Radiotherapy has been useful for pain-relief of the localized bone metastasis. The present intra-arterial infusion chemotherapy associated with radiotherapy was a possible local therapy for local recurrence of rectal cancer in the pelvis. Although the survival benefit depends on the presence of other site of recurrence, this procedure is useful for the improvement of QOL by relieving the pain of the patients.     

A case of advanced rectal cancer responding to l-Leucovorin (LV)/5-fluorouracil( 5-FU) therapy as neoadjuvant chemotherapy

We report a case in which l-Leucovorin/5-fluorouracil (l-LV/5-FU) therapy was remarkably effective for advanced rectal cancer as neoadjuvant chemotherapy (NAC). A 54-year-old man complained of bloody stool and constipation,and was diagnosed as having stage IIIB advanced rectal cancer with N2 lymphnode metastases on July 31, 2003. Two cycles of NAC by l-LV/5-FU therapy were performed. On abdominal computed tomography (micro CT), the primary lesion in the rectum decreased 82% and the metastatic lymphnodes had disappeared. As we established a diagnosis of the downstaging for stage II, a lower anterior resection with D3 lymphnode dissection was performed on December 5, 2003. The pathological examination demonstrated II, mod, 1.8 x 2.2 cm, a1, ly1,v0, ow(-), aw(-), n0, stage II. We could allow curability-A resection. The pathological effect of chemotherapy was grade 2 in which cancer cells became necrotic, suggesting apoptosis. The postoperative course was good. Postoperatively, 3 cycles of l-LV/5-FU therapy were performed. Although the patient had to be followed with internal use of 5-FU 200 mg/day as an outpatient from June 2, 2004, to date, there has been no sign of recurrence during the 12-month follow-up after the operation. Moreover, no adverse by chemotherapy was seen during the treatment. Thus, NAC by this therapy may be useful for patients with advanced rectal cancer.     

A case of inoperable advanced gall bladder cancer responding to intra-arterial infusion of 5-fluorouracil (5-FU) and leucovorin (LV)

The prognosis in cases of inoperable advanced gall bladder cancer is poor. We report here a case of inoperable advanced gall bladder cancer that responded to treatment with continuous intra-arterial infusion of 5-FU and bolus injection of LV for biochemical modulation. The patient was an 81-year-old woman, who visited a nearby clinic with the chief complaints of general fatigue and right lateral abdominal pain. A mass lesion which occupied from the dorsal surface of the liver to the pancreatic head was found by ultrasonography, and she was referred to our hospital for further diagnosis and therapy. The diagnosis was advanced gall bladder cancer of Stage IVa (S2, N3, P0, H0, Hinf1, Dinf1). For the selective arterial infusion of anticancer drugs, the patient underwent intra-arterial cannulation into the common hepatic artery, with a connecting subcutaneous port for arterial infusion therapy. The treatment schedule for 5-FU and LV therapy consisted of continuous infusion of 5-FU of 333 mg/m2 for 72 hr and bolus injection of LV of 20 mg/m2 3 times at 24 hr intervals. This treatment was repeated every 2 weeks. No side effects were observed after the first administration during hospitalization, so the treatment was continued up to 17 times on an outpatient basis. A tumor response was seen in the primary lesion, No. 8 and No. 16 lymph node metastases. A partial response was observed for 13 months and the overall survival was 15 months. These findings may imply that treatment with intra-arterial infusion of 5-FU and LV can be an effective chemotherapy for prolongation of survival in patients with inoperable advanced gall bladder cancer.     

Superselective intra-arterial infusion therapy with docetaxel, cisplatin and 5-fluorouracil for head and neck cancer--for tongue cancer patients in comparison patients with other therapies

In order to cure head and neck cancer without resection, chemotherapy (superselective intra-arterial infusion therapy with DCF) was conducted by anterograde, superselective intra-arterial infusion of 50-60 mg/m(2) of DOC and 50-60 mg/m(2) of CDDP via the femoral artery on day 1 followed by continuous intravenous instillation of 600-750 mg/m(2)/day of 5-FU for 5 days from day 2. A total of 70 patients with advanced and recurrent cancer of the head and neck have been treated since April 2000. With the median follow-up duration of 1,017 days, the survival rate was 92.7% and the organ preservation rate was 90.1%. Almost no complications associated with this therapy were observed. Due to space limitations, here we report only cases of tongue cancer. Histological CR was obtained from all 19 patients with squamous cell cancer of the tongue. With the median follow-up duration of 1,371 days (45.7 months: 471-2, 133 days), the survival rate was 94.74% and the organ preservation rate was 88.42% by the Kaplan-Meier method. For both the survival rate and organ preservation rate, extremely good results were obtained by the superselective intra-arterial infusion therapy with DCF compared to the intravenous infusion therapy using a combination of CDDP and 5-FU (five-year survival rate: 20%) as well as the superselective intra-arterial infusion of CDDP alone followed by continuous intravenous infusion of 5-FU (five year survival rate: 28.5%) that had been conducted before. Major adverse effects observed were leukopenia and alopecia. Although patients who underwent concurrent radiation therapy developed mucositis and dermatitis, both were reversible changes.     

Neoadjuvant chemotherapy with intra-arterial infusion in the treatment of advanced cervical cancer

Neoadjuvant chemotherapy (NAC) with intra-arterial infusion was performed in the treatment for 53 patients with advanced cervical squamous cell carcinoma. After NAC with intra-arterial infusion of the anticancer agents including cisplatin via internal iliac artery or uterine artery, 42 patients received radical hysterectomy. The response to therapy was observed in 45 of all patients (84.9%) clinically, and 36 of 42 patients (85.7%) pathologically. Cancer cells disappeared in 11.9% of patients with cervical invasion, 69.2% with vaginal wall invasion and 39.4% with parametrium invasion after NAG. Five-year survival rates were 100% in stage I, 71.5% in stage II, 52.2% in stage II and 0% in stage IV. The group of patients without cancer in the parametrium after NAC showed a significantly better 5-year survival rate than the group with residual cancer in the parametrium. According to the results, the elimination of cancer invasion to the parametrium by NAC is thought to be important for improvement of the prognosis in advanced cervical cancer.     

A case of advanced gastric cancer with multiple liver metastases partially responding to combination intra-arterial chemotherapy via the hepatic artery and abdominal aorta]

A 57-year-old female diagnosed with advanced gastric cancer with multiple organ metastases was treated by various intra-arterial chemotherapies. After surgical resection of the tumor, adjuvant chemotherapy was carried out. Continuously administered 5-fluorouracil of 250 mg/day made it possible to control the growth of the liver metastases. Extrahepatic metastases were kept under control by administering 30 mg of methotrexate, 750 mg of 5-fluorouracil and 30 mg of Leucovorin per/day/week, and 60 mg/day biweekly of cisplatinum via an abdominal artery infusion port. Owing to this multiple infusion route and chemotherapy regimen, the patient lived for 18 months after her first diagnosis of gastric cancer with multiple liver metastases. Although liver metastases may respond to hepatic arterial infusion chemotherapy, extrahepatic metastases lead to poor prognosis. Given the above results, intra-abdominal aorta chemotherapy may be effective for extrahepatic metastases since this method gives high concentration of the anticancer agents at tumor sites with a low incidence of side effects.     

Complete remission in a case of sigmoid colon cancer with multiple liver metastases-treatment with arterial chemotherapy and percutaneous microwave coagulation therapy

A 59-year-old man was admitted to our hospital for advanced sigmoid colon carcinoma with synchronous multiple liver metastases. The patient received sigmoidectomy with regional lymph node dissection on June 8, 1998. We started intra-arterial combination chemotherapy on July 1, 1998. MMC (4 mg/body) was administered via rapid intra-arterial infusion on day 1. After MMC administration, 5-day intra-arterial continuous infusion of 5-FU at 500 mg/body/day was performed with oral administration of LV (30 mg/body/day). The treatment cycle was defined as every three weeks. The patient was treated with 4 courses of chemotherapy. From September 30, he received intra-arterial infusion of bolus MMC 4 mg/body, LV 6 mg/body and 5-FU 1,000 mg/body/4 hrs every two weeks with oral administration of Tegafur-uracil 400 mg/day. After 4 intra-arterial chemotherapy sessions, the metastatic liver tumors disappeared except for a focus in the right lobe. Therefore we decided to give the remnant liver metastasis percutaneous microwave coagulation therapy (PMCT). He obtained a complete remission in the liver metastases after two PMCT (70 W, 60 sec) sessions. Intra-arterial chemotherapy is effective for unresectable metastatic liver tumors from colon cancer. If a patient shows a partial response on the metastatic tumors through the chemotherapy, one must consider other modalities such as PMCT.     

A case report of bilateral liver metastasis from rectal cancer effectively treated with continuous infusion of anti-cancer drugs through hepatic artery

A 52-year-old woman with bilateral liver metastasis originating from rectal cancer was treated with transarterial infusion of cisplatin, MMC, 5-FU and ADM after abdomino-peritoneal resection of the rectum. Cisplatin was infused continuously for 72 hours up to a 150 mg of dose through a Port-A-Cath which was inserted via gastro-duodenal artery at operation. The side effects observed were nausea, vomiting and leukopenia, but renal dysfunction was not encountered. Histology of the rectal lesion revealed poorly differentiated adenocarcinoma. The liver lesions were followed up by Echo, CT and angiography after chemotherapy, which demonstrated remarkable reduction in size or disappearance of the tumors.     

直肠癌根治术后行多动脉联合化疗对预防复发和转移的价值

目的观察肠系膜上动脉、髂内动脉及肝固有动脉联合化疗对直肠癌根治性切除术后患者肿瘤复发和转移的预防效果.方法随机选取103例直肠癌根治性切除术后患者分为两组,治疗组56例,以肠系膜上动脉、髂内动脉及肝固有动脉为靶血管,采用介入导管技术分别注入化疗药物5-氟尿嘧啶+丝裂霉素C+顺铂.对照组47例,术后采用全身静脉化疗,用药同治疗组.治疗后每组均随访5年,观察术后1～5年内肿瘤复发和转移的部位及数量.结果治疗组5年内共复发和转移18例,复发和转移率为32.1%(18/56),对照组复发和转移共22例,复发和转移率为47.0%(22/47),两组复发和转移率相比差异显著(P＜0.01).结论肠系膜上动脉、髂内动脉及肝固有动脉联合化疗对直肠癌根治性切除术后患者肿瘤复发和转移有预防作用.     

进展期胃癌动静脉结合的术前化疗

为提高术前化疗的疗效,我们探索动静脉结合的化疗方法。静脉缓慢输注时间依赖性药物以维持其作用时间,动脉局部注射浓度依赖性药物以提高其局部浓度,以不同的给药途径充分发挥两类药物的药理作用。2002年以动静脉结合的FLEP疗法（静脉缓慢注射5-FU与亚叶酸钙,动脉局部注射足叶乙甙与顺铂）应用于临床,取得了满意的初步效果。其后以毒性较低的奥沙利铂代替顺铂,使化疗的毒性明显降低。随后又在动脉给药中加入表阿霉素,使动脉给药形成了类似于EAP方案的EEOX给药方案,形成动静脉结合的FLEEOX（静脉缓慢注射5-FU与亚叶酸钙,动脉局部注射足叶乙甙、表阿霉素与奥沙利铂）方案。临床实践表明该方案的局部作用非常剧烈,使化疗有效率超过80%,对局部进展期胃癌的疗效明显优于传统途径的化疗。      

Intra-arterial infusion chemotherapy for advanced bladder cancer and prostate cancer using reservoir system

Eight patients with bladder cancer and two patients with prostate cancer were given intra-arterial infusion chemotherapy using the reservoir system. The tip of the catheter was inserted through the femoral artery to the common iliac artery and we compressed both femoral arteries during infusion. Five patients with locally advanced bladder cancer and two patients with prostate cancer were evaluated for the clinical and pathological efficacy of the treatment. Clinically, the efficacy of four of the five patients with bladder cancer was CR or PR and pathologically (according to Shimosato's criteria), the efficacy was two in IVb or III, and three in IIb. Clinically, the efficacy in two patients with prostate cancer was CR or PR, and pathologically the efficacy was IVb or IIb. Three patients had complications of the reservoir system. These results suggest that good therapeutic efficacy and an improved quality of life can be obtained by intra-arterial chemotherapy using the reservoir system.