Yoshitaka Inaba

Radiologic placement of side-hole catheter with tip fixation for hepatic arterial infusion chemotherapy.

PURPOSE To investigate the technical outcome of radiologic catheter placement with use of a side-hole catheter with distal fixation for hepatic arterial infusion chemotherapy. MATERIALS AND METHODS Between January 1993 and September 1999, 426 patients were referred to our department to undergo intraarterial infusion chemotherapy for unresectable malignant liver tumors. A subclavian artery was exposed under local anesthesia and a catheter was inserted. After inserting the tip of the side-hole catheter into the gastroduodenal artery, splenic artery, or peripheral branch of the hepatic artery, the catheter tip was fixed to the vessel with use of coils and a mixture of n-butyl cyanoacrylate (NBCA) and iodized oil. The proximal end of the catheter was connected to an implanted port, and the port system was embedded subcutaneously. RESULTS Placement was successful in 425 of 426 patients (99.8%) in a mean time of 76 minutes. Catheter dislodgement was noted in 12 patients (2.8%). Cumulative patency rates of the hepatic artery calculated according to the Kaplan-Meier method for the entire group were 91.0%, 81.4%, and 58.1% at 6 months and 1 and 2 years, respectively. Complications related to catheter placement were observed in nine cases and included dysfunction of the implanted system (n = 3), significant bleeding around the implanted port (n = 2), improper infusion of NBCA and iodized oil (n = 2), and cerebral infarction (n = 2). CONCLUSION Radiologic catheter placement via a subclavian artery with side-hole catheter placement with distal fixation for hepatic arterial infusion chemotherapy is a highly successful procedure with a reduced risk of catheter dislodgment and arterial occlusion.

Intermittent hepatic arterial infusion of high-dose 5FU on a weekly schedule for liver metastases from colorectal cancer.

Purpose: We performed phase I and II studies to examine the usefulness of intermittent hepatic arterial infusion of high-dose 5-fluorouracid (5-FU) for patients with liver metastasis from colorectal cancer. Methods: As the phase I study, 1000, 1250 and 1500 mg/m2 of 5-FU were administered over 5 h by hepatic arterial infusion on a weekly schedule to establish the recommended dose. Based on the results of the phase I study, the phase II study was performed to confirm the efficacy of the recommended dose thus obtained. Results: In the phase I study, the dose-limiting factors of this therapy were gastrointestinal and central nervous system toxicities, and the recommended dose was judged to be 1000 mg/m2. In the phase II study, 1000 mg/m2 of 5-FU was administered over 5 h once a week on an outpatient basis, and this therapy was repeated as long as possible. The response rate was 78% (25/32), with an overall median survival time of 25.8 months (without extrahepatic lesions 25.9 months; with extrahepatic lesions 17.3 months). Conclusions: (1) Compared with conventional continuous infusion, the advantages of this therapy were that it caused no decrease in the patients quality of life as a result of being permanently equipped with a pump and it thus enabled more cost-effective use of the pump, (2) The phase II study on 32 patients showed that this therapy caused no serious toxicities, with a response rate of 78% and a survival time of 25.8 months, which exceeded the results with conventional continuous infusion. If the reproducibility of these results is established in further studies involving multicenter collaboration, this therapy will be able to become the standard local chemotherapy for liver metastases from colorectal cancer. (3) Important problems remaining to be solved are improvement of the technical aspects and studies of combined use with systemic chemotherapy. Furthermore, to finally determine the position of this therapy in the treatment system for liver metastasis from colorectal cancer, it is necessary to conduct comparative trials versus systemic chemotherapy, using the survival time as the end-point.

Neutropaenia as a prognostic factor in metastatic colorectal cancer patients undergoing chemotherapy with first-line FOLFOX

We retrospectively analysed 153 patients with metastatic colorectal cancer who received FOLFOX with or without bevacizumab as first-line chemotherapy. Several background characteristics and chemotherapy features (grade of neutropaenia, use of bevacizumab or irinotecan, re-introduction of FOLFOX, and tumour progression) as time-varying covariates were analysed as potential prognostic factors. Of the 153 patients, mild neutropaenia (grade 1-2) occurred in 60 patients (39%) and severe neutropaenia (grade 3-4) occurred in 46 patients (30%). The other 47 patients (31%) did not experience neutropaenia. According to a multivariate Cox model with time-varying covariates, hazard ratios (HRs) of death were 0.55 (95% confidence interval (CI), 0.31-0.98; P=0.044) for patients with mild neutropaenia and 0.35 (95% CI, 0.18-0.66; P=0.002) for those with severe neutropaenia. Both mild and severe neutropaenia during chemotherapy are associated with improved survival in patients with MCRC. Prospective trials are required to assess whether dosing adjustments based on neutropaenia may improve chemotherapy efficacy.

Right Gastric Artery Embolization to Prevent Acute Gastric Mucosal Lesions in Patients Undergoing Repeat Hepatic Arterial Infusion Chemotherapy

PURPOSE The purpose of the study was to investigate the technical outcome and clinical effect of right gastric artery (RGA) embolization to prevent acute gastric mucosal lesions caused by influx of anticancer agents into the RGA in patients undergoing repeat hepatic arterial infusion chemotherapy (HAIC). MATERIALS AND METHODS In 217 patients with malignant hepatic tumors, we attempted RGA embolization with use of metallic coils and/or a mixture of n-butyl cyanoacrylate (n-BCA) and iodized oil, along with the embolization of the gastroduodenal artery. After this procedure, an infusion catheter was placed radiologically and HAIC was performed. We then evaluated the technical outcome and clinical effect of RGA embolization. RESULTS RGA embolization was technically successful in 201 of 217 patients (93%). Major complications--nausea, epigastric pain, and fever--were noted in 12%, 4%, and 2% of successful cases, respectively, and were treated conservatively. Recanalization occurred in 4% (nine of 201) of the patients. Eventually, sufficient RGA embolization was achieved in 192 patients. The incidence of acute gastric mucosal lesions confirmed endoscopically was only 3% (five of 192) in patients with sufficient RGA embolization, whereas it was 36% (nine of 25) in patients without sufficient RGA embolization, with a significant difference (P <.01). CONCLUSION RGA embolization is a highly feasible procedure that can reduce the incidence of acute gastric mucosal lesions associated with HAIC.

A Randomized Phase II/III Trial Comparing Hepatectomy Followed by mFOLFOX6 with Hepatectomy Alone as Treatment for Liver Metastasis from Colorectal Cancer: Japan Clinical Oncology Group Study JCOG0603

A randomized controlled trial is being conducted in Japan to compare hepatectomy alone with hepatectomy followed by adjuvant chemotherapy as treatment in patients with curatively resected liver metastases from colorectal cancer to improve survival with intensive chemotherapy. Between 42 and 70 days after liver resection, patients are randomly assigned to either hepatectomy alone or hepatectomy followed by 12 cycles of modified FOLFOX6 (mFOLFOX6) regimen. A total of 300 patients (including 78 patients in Phase II) will be accrued from 38 institutions within 3 years. The primary endpoint is treatment compliance at nine courses of mFOLFOX6 regimen in Phase II and disease-free survival in Phase III. The secondary endpoints are overall survival, incidence of adverse events and patterns of recurrence.

Management of patients with unresectable liver metastases from colorectal and gastric cancer employing an implantable port system

SummaryBetween 1985 and 1990, 50 patients with unresetable liver metastases from colorectal cancer and 34 subjects with metastases from gastric cancer were treated by repeated hepatic arterial infusion chemotherapy employing an implantable prot system. A catheter was inserted into the hepatic artery via the left subclavian artery and was connected to the implantable injection port in each patient. 5-Fluorouracil (5-FU) at 330 mg/m2 per week (167 mg/m2 daily given continuously over the initial 3 months for colorectal cancer), Adriamycin (ADR) at 20 mg/m2 every 4 weeks and mitomycin C (MMC) at 2.7 mg/m2 every 2 weeks were given to all 34 patients with gastric cancer and to 31 of the colorectal cancer patients. The remaining 19 patients with colorectal cancer received 5-FU at 1.000 mg/m2 every week. As a rule the treatment was performed on an outpatient basis. The side effects and complications observed included myelosuppression (23%), hepatic arterial occlusion (21%), and gastroduodenal mucositis (12 %), although no major toxicity was encountered. The response rate (CR+PR) among the evaluated patients as detemined using CT scans was 67% for colorectal cancer and 73% for gastric cancer. The overall median survival was 12 months and 15 months, respectively. Good local control of liver metastases from the colorectal and gastric cancers was achieved by repeated hepatic arterial infusion chemotherapy employing an implantable port system without the need for hospitalization and without producing major toxicity. Thus, the implantable port system is very useful for the management of patients with unresectable liver metastases.

Prospective Study of Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: An Asian Cooperative Study between Japan and Korea

PURPOSE To evaluate the safety and efficacy of transcatheter arterial chemoembolization used for the treatment of unresectable hepatocellular carcinoma (HCC) with an Asian cooperative prospective study between Japan and Korea. MATERIALS AND METHODS Patients with unresectable HCC unsuitable for curative treatment or with no prior therapy for HCC were enrolled. The patients underwent transcatheter arterial chemoembolization with emulsion of Lipiodol and anthracycline agent, followed by embolization with gelatin sponge particles, which was repeated on an as-needed basis. The primary endpoint was 2-year survival rate, and the secondary endpoints were adverse events and response rate. RESULTS The 2-year survival rate of 99 patients was 75.0% (95% confidence interval, 65.2%-82.8%). The median time-to-progression was 7.8 months, and the median overall survival period was 3.1 years. Of 99 patients, 42 (42%) achieved a complete response, and 31 (31%) had a partial response. The response rate was 73% using modified Response Evaluation Criteria in Solid Tumors. The grade 3-4 toxicities included increased alanine aminotransferase level in 36%, increased aspartate aminotransferase level in 35%, thrombocytopenia in 12%, and abdominal pain in 4% of patients. All other toxicities were generally transient. CONCLUSIONS Asian transcatheter arterial chemoembolization demonstrated sufficient safety and reasonable efficacy as a standard treatment for unresectable HCC. These results could be useful as reference data for future trials of transcatheter arterial chemoembolization.

Transcatheter Arterial Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres for Colorectal Liver Metastases after FOLFOX Failure: Results of a Phase I/II Study

PURPOSE To report the results of a phase I/II study of a transcatheter arterial chemoembolization protocol using cisplatin powder and degradable starch microspheres (DSM) for unresectable colorectal liver metastases after failure of FOLFOX (5-flourouracil, leucovorin plus oxaliplatin) chemotherapy conducted to determine the recommended dose of cisplatin powder and to assess the efficacy and safety of the protocol. MATERIALS AND METHODS A fine-powder formulation of cisplatin was mixed with DSM and administered via the hepatic artery every 4 weeks. In phase I, three cohorts of patients received escalating doses of cisplatin powder: 50 mg/m(2), 65 mg/m(2), and 80 mg/m(2). In phase II, tumor response, toxicity, and survival times were assessed. RESULTS The study enrolled 24 patients. Previously, FOLFOX had been administered to all patients, an irinotecan-containing regimen had been administered to 12 patients, and bevacizumab or cetuximab or both had been administered to 14 patients. In phase I, dose-limiting toxicity did not appear at any level, and the recommended dose of cisplatin powder was determined to be 80 mg/m(2). In phase II, a tumor response rate of 61.1% was achieved. The median hepatic progression-free survival and overall survival were 8.8 months (95% confidence interval [CI], 4.06-13.5 mo) and 21.1 months (95% CI, 8.37-33.8 mo). The following grade 3 toxicities were observed: thrombocytopenia (12.5%), aspartate transaminase elevation (33.3%), alanine transaminase elevation (12.5%), hyponatremia (8.3%), and cholecystitis (4.2%). CONCLUSIONS This study shows that transcatheter arterial chemoembolization with cisplatin powder at a dose of 80 mg/m(2) mixed with DSM is well tolerated and can produce a high response rate with a long survival time for patients with unresectable colorectal liver metastases after failure of FOLFOX.

Phase I/II clinical study of percutaneous vertebroplasty (PVP) as palliation for painful malignant vertebral compression fractures (PMVCF): JIVROSG-0202

BACKGROUND The safety and efficacy of percutaneous vertebroplasty (PVP), a new treatment modality for painful malignant vertebral compression fractures (PMVCF) using interventional radiology techniques, were evaluated prospectively. MATERIALS AND METHODS After confirming the absence of safety issues in phase 1, a total of 33 cases were registered up to and including phase 2. Safety and efficacy were evaluated by National Cancer Institute-Common Toxicity Criteria version 2 and Visual Analogue Scale (VAS) at 1 week after PVP. Based on VAS score decreases, efficacy was classified into significantly effective (SE; > or = 5 or reached 0-2), moderately effective (ME; 2-4), or ineffective (NE; <2 or increase). RESULTS Procedures were completed in all 33 patients (42 vertebrae). Thirty days after PVP, two patients died of primary disease progression, but no major adverse reactions (>grade 2) were observed. Response rate was 70% (95% confidence interval 54% to 83%) [61% (n = 20) with SE, 9% (n = 3) with ME, and 30% (n = 10) with NE] and increased to 83% at week 4. Median time to response was 1 day (mean 2.4). Median pain-mitigated survival period was 73 days. CONCLUSION For PMVCF, PVP is a safe and effective treatment modality with immediate onset of action.

Hepatic arterial infusion chemotherapy for liver metastases from breast cancer

Between 1985 and 1992, 56 patients with unresectable liver metastases from breast cancer were treated by repeated hepatic arterial infusion chemotherapy employing an implantable port system. 5-Fluorouracil (5-FU) at 330 mg/m2 per week, Adriamycin (ADR) at 20 mg/m2 every 4 weeks, and mitomycin C (MMC) at 2.7 mg/m2 every 2 weeks were given to 42 patients. The remaining 14 patients received 5-FU at 330 mg/m2 per week and epirubicin (EPIR) at 20 mg/m2 every 2 weeks. As a rule, the treatment was performed on an outpatient basis. The side effects and complications observed included myelosuppression (41%), hepatic arterial occlusion (23%), and gastric mucositis (20%), but no major toxicity was encountered. The response rate (CR+PR) of the evaluated patients as determined from CT scans was 81%. The overall median survival period was 12.5 months. Only 14% of the patients died due to regrowth of liver metastases, and in 70% of the total cases, death due to liver metastases was avoided by this treatment. Thus, repeated hepatic arterial infusion chemotherapy for liver metastases from breast cancer might be capable of prolonging the survival of patients via avoidance of death due to the liver metastases.