Phase I/II randomized trial of intrahepatic arterial infusion chemotherapy with cisplatin and chemoembolization with cisplatin and polyvinyl sponge in patients with ocular melanoma metastatic to the liver (original) (raw)
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Tumori Journal, 1994
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 intraarterial hepatic carboplatin-based chemotherapy at the dose of 300 mg/m2 once every two weeks at an outpatient 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 intraarterial hepatic chemotherapy and active in ocular melanoma metastic to the liver.
Melanoma research, 2016
Uveal melanoma patients have a poor survival after the diagnosis of metastatic disease. Isolated hepatic perfusion (IHP) was developed to treat patients with unresectable metastases confined to the liver. This retrospective analysis focuses on treatment characteristics, complications, toxicity and survival after IHP. Patients with uveal melanoma metastases confined to the liver treated with IHP in two experienced hepato-pancreatic-biliary surgery centres (Erasmus MC Cancer Institute and Leiden University Medical Center) were included. Between March 1999 and April 2009, 30 patients were treated with IHP. The duration of surgery was 3.7 h (Erasmus MC Cancer Institute) versus 8.7 h (Leiden University Medical Center) and also the dosage of melphalan differed: 1 mg/kg body weight (n=12) versus a dose of 170-200 mg (n=18) or melphalan (100 mg) combined with oxaliplatin (50 or 100 mg) (n=3). The length of hospital stay was 10 days. Two patients developed occlusion of the hepatic artery and...
In vivo (Athens, Greece)
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and the liver is the predominant site of metastases (LM). If metastases appear, none of the systemic treatments established for cutaneous melanoma so far have any significant impact. Several authors have adopted transarterial chemoembolization (TACE) as palliation. TACE combines hepatic artery embolization with infusion of concentrated doses of chemotherapeutic drugs. DC Beads are new embolic products that can be loaded with irinotecan (IRI). The beads consist of polyvinyl alcohol microspheres modified with sulfonic acid groups and are available at different size ranges from 100 to 900 microns in diameter. The use of IRI as drug-eluting beads seems to optimize TACE in UM. Our purpose was to assess the safety and efficacy of this new kind of TACE in a phase II clinical study. Ten patients with LM from UM were treated with TACE-containing beads preloaded with IRI (100 mg). All patients had an objective res...
European Journal of Surgical Oncology (EJSO), 2009
Aim: Ocular melanoma prefers to metastasize to the liver and the liver is the sole site of metastatic disease in 80% of patients. Until now there has been no standard treatment available and these patients have a very poor prognosis (median survival 2e5 months). Isolated hepatic perfusion may be an option in patients with irresectable hepatic ocular melanoma metastases. The aim of this study was to evaluate applicability, toxicity and response in this selected group of ocular melanoma patients by treatment with isolated hypoxic hepatic perfusion with retrograde outflow (IHHP) with melphalan. Methods: From September 2002 until July 2006 eight consecutive patients were included in this study. IHHP was performed with inflow via the hepatic artery and retrograde outflow via the portal vein during 25 min with 1 mg/kg melphalan. The perfusion was followed by a complete wash-out procedure. Results: The median total operation time was 4 h with a median blood/fluid loss of 1100 ml. No postoperative mortality was observed. Median hospital stay was 9.5 days. Toxicity was moderate: WHO grade 3 leukocytopenia in 3 patients, grade 3 hepatic toxicity in 1 patient. In 37% of patients (3/8) a partial response could be demonstrated 3 months after IHHP. Stable disease was found in 3 patients and progressive disease in 2 patients. Median time to local progression was 6 months and the median survival was 11 months. Conclusion: Melphalan-based IHHP with retrograde outflow is a safe treatment option for patients with irresectable ocular melanoma metastases. Survival benefit seems to be comparable to classical IHHP.
Journal of Surgical Oncology, 2017
Background: Metastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence. Available systemic treatments have not improved outcomes. Melphalan percutaneous hepatic perfusion (M-PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy. Methods: Retrospective analysis of outcomes data of UM patients receiving M-PHP at two institutions was performed. Tumor response and toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) v4.03, respectively. Results: A total of 51 patients received 134 M-PHP procedures (median of 2 M-PHPs). 25 (49%) achieved a partial (N = 22, 43.1%) or complete hepatic response (N = 3, 5.9%). In 17 (33.3%) additional patients, the disease stabilized for at least 3 months, for a hepatic disease control rate of 82.4%. After median follow-up of 367 days, median overall progression free (PFS) and hepatic progression free survival (hPFS) was 8.1 and 9.1 months, respectively and median overall survival was 15.3 months. There were no treatment related fatalities. Non-hematologic grade 3-4 events were seen in 19 (37.5%) patients and were mainly coagulopathic (N = 8) and cardiovascular (N = 9). Conclusions: M-PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Cancers
Background: Uveal melanoma is the most commonly occurring primary intraocular malignancy in adults, and patients have a high risk of developing metastatic disease, mostly in the liver. Isolated hepatic perfusion (IHP) with melphalan is a liver-directed therapy for patients with liver metastases. Percutaneous hepatic perfusion (PHP), a minimally invasive technique, is available as well. PHP benefits from the fact that the procedure can be repeated and therefore possibly offers better survival. We conducted a systematic review and meta-analysis comparing both techniques. Methods: A systematic literature search was performed using the electronic databases of Scopus, MEDLINE, Web of Science, PubMed and Cochrane CENTRAL. A total of nine articles reporting on eight studies were included in the analysis. Individual survival data were extracted from each study. Results: The median overall survival (OS) was 17.1 months for IHP and 17.3 months for PHP. The median progression-free survival (PF...
Isolated hepatic perfusion for liver metastases of malignant melanoma
Melanoma Research, 2008
The objective was to analyze the outcome of three treatment strategies using isolated hyperthermic liver perfusion (IHP) with melphalan for liver metastases of malignant melanoma. It was designed as an exploratory study. The setting was a single-center study in a university hospital. The study was carried out on 27 patients. IHP was used with modifications during three different time periods (IHP I, IHP II and IHP III), in technique and temperature (amount of melphalan: 0.5, 1.0 and 2 mg/kg body weight in the perfusate; 41, 40 and 408C). Tumor response was estimated according to WHO criteria with computed tomography or MRI. Mortality and morbidity were secondary measures. Six of 11 patients in the IHP I cohort experienced a partial response (PR). In the IHP II cohort, two patients of 11 experienced a complete response and five a PR. In the IHP III cohort, five of five patients experienced a PR. Six postoperative deaths were reported (27%) (three in the IHP I and three in the IHP II series), secondary to liver insufficiency and multiorgan failure. Treatment of liver metastases of malignant melanoma with isolated hyperthermic melphalan perfusion has shown an impressive tumor response rate, which seems to be higher than the response rates reported for other systemic chemotherapy regimens. The maximum tolerated dose for melphalan in the perfusate was surpassed with a 2 mg/kg body weight. By modifying the technique and restricting the allowed tumor burden, the response rate remained high and the mortality was reduced. Melanoma
Cancer Chemotherapy and Pharmacology, 2010
Purpose We conducted a phase I study of hepatic arterial infusion (HAI) cisplatin and systemic chemotherapy in patients with advanced cancer and dominant liver involvement. Methods Patients were treated with HAI cisplatin 100–125 mg/m2 (and 3,000 IU heparin) intraarterially and liposomal doxorubicin (doxil) 20–35 mg/m2 IV (day 1) every 28 days. A “3 + 3” study design was used. Results Thirty patients were treated (median age, 56 years). Diagnoses were breast cancer (n = 11), colorectal cancer (n = 8), ocular melanoma (n = 4), and other (n = 7). The median number of prior therapies was 5. The maximum tolerated dose (MTD) was at the 100/35 mg/m2 level. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (n = 1) at the cisplatin 125 mg/m2 and systemic doxil 35 mg/m2 dose level. The most common toxicities were nausea/vomiting and fatigue. Of 24 patients evaluable for response, 4 (17%) had a partial response (PR) and 7 (29%) had stable disease (SD) for ≥4 months. Of the 11 patients with breast cancer, 3 (27%) had a PR and 5 (45%) had SD for ≥4 months. Of 4 patients with ocular melanoma, 1 had a PR and 1 SD for 4 months. One patient with hepatocellular carcinoma had SD for 4 months. Of 12 evaluable patients treated at the MTD, 2 (17%) had a PR and 5 (42%) had SD. Conclusion The MTD was HAI cisplatin 100 mg/m2 and systemic doxil 35 mg/m2. This regimen demonstrated antitumor activity, especially in breast cancer.
American journal of clinical oncology, 2017
Regional therapy for metastatic melanoma to the liver represents an alternative to systemic therapy. Hepatic progression-free survival (HPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. A retrospective review of patients with liver metastases from cutaneous or uveal melanoma treated with yttrium-90 (Y90), chemoembolization (CE), or percutaneous hepatic perfusion (PHP) was conducted. Thirty patients (6 Y90, 10 PHP, 12 CE, 1 PHP then Y90, 1 CE then PHP) were included. Multivariate analysis showed improved HPFS for PHP versus Y90 (P=0.004), PHP versus CE (P=0.02) but not for CE versus Y90. PFS was also significantly different: Y90 (54 d), CE (52 d), PHP (245 d), P=0.03. PHP treatment and lower tumor burden were significant predictors of prolonged PFS on multivariate analysis. Median OS from time of treatment was longest, but not significant, for PHP at 608 days versus Y90 (295 d) and CE (265 d), P=0.24. Only PHP treatment versus Y90 and lower tumor burde...