RESUMEN
AIMS: Twenty-three patients with liver metastases from colorectal cancer were entered into a prospective, phase II pilot study to evaluate the efficacy and feasibility of intra-arterial high-dose chemotherapy (IAHC) + intraperitoneal chemotherapy (IPC) combined with hemofiltration. METHODS: All patients had abdominal laparotomy to position a hepatic artery infusion port and in 15 cases an implantable system for IPC. A double-lumen filtration catheter was placed in the vena cava via the saphenous or femoral vein and connected to a modified hemofiltration unit. The treatment schedule consisted of mitomycin (30-50 mg/m2) and epirubicin (60-90) mg/m2) as IAHC combined with cisplatin (60 mg/m2) given in a 2000 ml saline solution by IPC. The high-dose IAHC-IPC was followed by 4 cycles of intra-arterial standard dose chemotherapy through the arterial port-a-cath (6 mg/m2 mitomycin and 20 mg/m2 epirubicin) and if possible by another cycle of high dose IAHC-IPC. RESULTS: We delivered a total of 31 cycles of IAHC, 21 of which were combined with IPC. Ten cycles of IAHC were administered without concurrent IPC because of painful adhesions, clinical contraindications or patient refusal. Seven of 23 patients (30%) were pretreated and with progressive disease after systemic chemotherapy. Among 22 evaluable patients, we obtained 2 complete remissions (9%) and 11 partial remissions (50%); moreover, 4 of 7 pretreated patients obtained a response to treatment. As a result, an objective tumor response was observed in 59% of patients (13/22). Therefore, a dose-response behavior was demonstrated also in tumors with a low chemosensitivity. The median duration of response and survival was 10 and 14 months, respectively. Toxicity was usually mild, but we reported one toxic death due to treatment complications. CONCLUSIONS: Further prospective randomized studies are needed to confirm the results of our study.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Hemofiltración , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Infusiones Intraarteriales , Inyecciones Intraperitoneales , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
INTRODUCTION: Liver invasion is the major cause of organ failure in patients with primary liver cancer and metastatic large bowel cancer. Furthermore it causes high morbidity in many other carcinomas. The normal liver presents a double circulation: 75% from portal circulation and 25% from hepatic artery. In malignant primary and secondary lesions the blood support is given by hepatic artery. Antineoplastic drugs mixed to selectively injecting embolic particles, such as polyvinyl alcohol and gelatin powder (Gelfoam), can be injected to infarct tumors and to obtain a therapeutical advantage. Chemoembolization using an emulsion of Lipiodol ultra-fluid (LUF) and drugs is a recent tool in liver regional therapy. LUF has been shown to be taken up hepatocellular carcinoma and retained for a long period of time in the tumor bed. Chemoembolization causes massive shrinkage due to ischemia and increasing the local drug intensity and drug exposure. Our study reports the results of multi-agents chemoembolization (MACHEM) in 17 patients bearing massive liver involvement. MATERIAL AND METHODS: From January 1988 we treated 17 patients (5 HCCs, 7 large bowell carcinomas, 1 gastric cancer, 1 ocular melanoma, 1 pancreas, 1 soft tissue sarcoma, 1 carcinoid) using a transfemoral approach to cannulate the celiac axis and then the hepatic artery. The catheter was advanced into the vessel responsible for the majority of the tumor blood supply and a mixture of Gelfoam, radiopaque contrast media, followed by chemotherapy (mitomycin 10 mg/sqm, cisplatin 20 mg/sqm, epirubicin 20 mg/sqm) mixed to LUF was injected until vascular stasis occurred. After chemoembolization, analgesics and anti-pyretics were administered. Liver function tests were monitored daily. RESULTS: Objective tumor regression was observed in 11 out 15 full evaluable patients; the median duration of survival was 9.5 months. Within 8 weeks shrinkage, due to development of necrosis, appeared in the tumors. One patient with high levels of 5-HIAA due to carcinoid, demonstrated more than 75% decreasing in urinary excretion. In 6 patients out 8 with CEA elevation a clear reduction was documented as well in 2 HCCs out 5 with alfa-fetoprotein elevation. DISCUSSION: The palliation of HCC and metastatic liver disease have been extremely disappointing. Systemic chemotherapy produces in HCC a response rate of no more than 20% and does not increase the median survival. Venook obtained 24% of PRs and liquefaction in 35 out 50 HCC treated with chemoembolization. Some results have been also demonstrated in the treatment of metastatic liver tumors by Carrasco, Daniels and Modiano. Moertel stressed that chemoembolization could be incorporated in the initial management of carcinoid. Because of the difference in chemoembolization protocols it is difficult to compare the relative efficacy of this tool, although encouraging response rates have been reported in palliation of bulky tumors. In our study Gelfoam given before LUF and antineoplastic agents mixture produce a distal arteriolar occlusion and this would facilitate the migration of the polychemotherapy emulsion toward the tumor. Our MACHEM program has been shown to have significant activity even in heavily pretreated patients with an acceptable toxicity. We conclude that hepatic arterial chemoembolization will be improved by mean of better combination of chemotherapy with embolizing agents in well selected patients.
Asunto(s)
Carcinoma Hepatocelular/terapia , Embolización Terapéutica , Infusiones Intraarteriales , Neoplasias Hepáticas/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/mortalidad , Femenino , Estudios de Seguimiento , Esponja de Gelatina Absorbible , Humanos , Aceite Yodado/administración & dosificación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana EdadRESUMEN
AIMS AND BACKGROUND: ocular melanoma tends to metastasize to the liver, sparing for a long time the rest of the organism. Therefore, a regional treatment is especially indicated. METHODS: eight patients with ocular melanoma metastatic to the liver were treated with intra-arterial hepatic carboplatin-based chemotherapy at the dose of 300 mg/m2 once every two weeks at an out-patient clinic. All the patients were submitted to laparotomy with surgical implantation of an arterial port device through the gastroduodenal artery. RESULTS: the overall response rate was 38% with a median survival time of 15 months. The regimen was well tolerated and the principle toxicity was myelosuppression; any instance of hepatic and/or cholangitic damage was reported. CONCLUSIONS: Carboplatin seems suitable for intra-arterial hepatic chemotherapy and active in ocular melanoma metastatic to the liver.