melphalan and Uveal-Neoplasms

Patients with liver metastasis from uveal melanoma have a poor prognosis. Efficacy and safety of hepatic transarterial chemoembolization (TACE) using melphalan and microspheres was evaluated.. Monocentric retrospective study of all consecutive patients treated by TACE using melphalan and 250μm calibrated microspheres between 2004 and 2016. Radiological response was assessed according to RECIST 1.1, modified (m)-RECIST and EASL on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The primary endpoint was overall survival (OS). Liver metastasis response, hepatic, extrahepatic and global progression free survival (PFS) complications were evaluated with the common terminology criteria for adverse events version 4.0 (CTCAE 4.0) and survival factors were secondary endpoints.. Thirty-four patients underwent 138 TACE (4; 4.1 sessions; range 1-9). Median OS was 16.5 months (mean 21.6 months). Liver metastasis response combining partial and complete response was 42.4%, 97%, 97% with RECIST 1.1, mRECIST, EASL, respectively. There were 58 severe (CTCAE≥3) but manageable complications in 28 patients, except for 1 toxic death.. For patients with liver metastases from uveal melanoma ineligible for local treatments, TACE using melphalan may be performed as first line therapy in metastatic miliary disease from uveal melanomas with careful supportive care.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Antineoplastic Agents, Alkylating; Chemoembolization, Therapeutic; Female; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Microspheres; Middle Aged; Prognosis; Progression-Free Survival; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Treatment Outcome; Uveal Neoplasms

To improve isolated hepatic perfusion (IHP), we performed a phase I dose-escalation study to determine the optimal oxaliplatin dose in combination with a fixed melphalan dose.. Between June 2007 and July 2008, 11 patients, comprising of 8 colorectal cancer and 3 uveal melanoma patients and all with isolated liver metastases, were treated with a one hour IHP with escalating doses of oxaliplatin combined with 100 mg melphalan. Samples of blood and perfusate were taken during IHP treatment for pharmacokinetic analysis of both drugs and patients were monitored for toxicity, response and survival.. Dose limiting sinusoidal obstruction syndrome (SOS) occurred at 150 mg oxaliplatin. The areas under the concentration-time curves (AUC) of oxaliplatin at the maximal tolerated dose (MTD) of 100 mg oxaliplatin ranged from 11.9 mg/L h to 16.5 mg/L h. All 4 patients treated at the MTD showed progressive disease 3 months after IHP.. In view of similar and even higher doses of oxaliplatin applied in both systemic treatment and hepatic artery infusion (HAI), applying this dose in IHP is not expected to improve treatment results in patients with isolated hepatic metastases.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Cohort Studies; Colorectal Neoplasms; Female; Humans; Liver Neoplasms; Male; Maximum Tolerated Dose; Melanoma; Melphalan; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Treatment Outcome; Uveal Neoplasms

Uveal melanoma is the most common primary intraocular tumour in adults. After treatment of the primary tumour, up to 50% of patients will ultimately develop metastases. Treatment options for metastases are limited. When uveal melanoma metastases are confined to the liver, isolated hepatic perfusion (IHP) could be a treatment option. Herein, we report the results of a small group of patients with uveal melanoma metastases of the liver treated with IHP. Eight patients with uveal melanoma metastases confined to the liver underwent IHP with high-dose melphalan (200 mg) for 1 h. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria and tumour response was assessed according to World Health Organization criteria. The tumour response rate (complete or partial remission) was 50%. The median time to progression was 6.7 months (range, 1.7-16.9 months). The overall median survival was 9.9 months (range, 4.7-34.6 months), with a 1 year survival of 50% and a 2 year survival of 37.5%. Three patients experienced grade 3-4 hepatotoxicity which was transient within 3 months. Although only a small group of patients has been treated and evaluated so far, IHP is a treatment option for uveal melanoma metastases confined to the liver which can result in tumour responses and may lead to survival benefits in a selective group of patients.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Choroid Neoplasms; Disease Progression; Female; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Skin Neoplasms; Survival Rate; Time Factors; Treatment Outcome; Uveal Neoplasms

Topics: Humans; Melanoma; Melphalan; Uveal Neoplasms

Uveal melanoma, the most common primary ocular malignancy in adults, carries a poor prognosis: 50% of patients develop the metastatic disease with a 10-25% 1-year survival and no established standard of care treatment. Prior studies of melphalan percutaneous hepatic perfusion (M-PHP) have shown promise in metastatic uveal melanoma (mUM) patients with liver predominant disease but are limited by small sample sizes. We contribute our findings on the safety and efficacy of the procedure in the largest sample population to date. A retrospective analysis of outcome and safety data for all mUM patients receiving M-PHP was performed. Tumour response and treatment toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events v5.03, respectively. 250 M-PHP procedures were performed in 81 patients (median of three per patient). The analysis demonstrated a hepatic disease control rate of 88.9% (72/81), a hepatic response rate of 66.7% (54/81), and an overall response rate of 60.5% (49/81). After a median follow-up of 12.9 months, median overall progression-free (PFS) and median overall survival (OS) were 8.4 and 14.9 months, respectively. There were no fatal treatment-related adverse events (TRAE). Forty-three grade 3 (29) or 4 (14) TRAE occurred in 23 (27.7%) patients with a significant reduction in such events between procedures performed in 2016-2020 vs. 2012-2016 (0.17 vs. 0.90 per patient, P < 0.001). M-PHP provides excellent response rates and PFS compared with other available treatments, with decreasing side effect profile with experience. Combination therapy with systemic agents may be viable to further advance OS.

Topics: Adult; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Humans; Liver Neoplasms; Melanoma; Melphalan; Neoplasms, Second Primary; Perfusion; Retrospective Studies; Skin Neoplasms; Uveal Neoplasms

The aim of this study was to identify positive predictors for survival in uveal melanoma (UM) patients treated with percutaneous hepatic perfusion with melphalan (M-PHP), by retrospectively pooling data from three centers.. Retrospective analysis including patients ([Formula: see text] 18 years) treated with M-PHP between February 2014 and December 2019 for unresectable liver-dominant or liver-only metastases from UM. Predictors for OS were assessed using uni- and multivariate analyses. Other study outcome measures were response rate, progression-free survival (PFS), liver progression-free survival (LPFS), overall survival (OS) and complications according to CTCAEv5.0.. In total, 101 patients (47.5% males; median age 59.0 years) completed a minimum of one M-PHP. At a median follow-up time of 15.0 months, complete response (CR), partial response (PR), stable disease (SD) and progressive disease were seen in five (5.0%), 55 (54.5%), 30 (29.7%) and 11 (10.9%) patients, respectively, leading to a 89.1% disease control rate. Median PFS, LPFS and OS were 9.0, 11.0 and 20.0 months, respectively. Survival analyses stratified for radiological response demonstrated significant improved survival in patients with CR or PR and SD category. Treatment of the primary tumor with radiotherapy, ≥ 2 M-PHP and lactate dehydrogenase (LDH) < 248 U/L were correlated with improved OS. Thirty-day mortality was 1.1% (n = 2). Most common complication was hematological toxicity (self-limiting in most cases).. M-PHP is safe and effective in patients with UM liver metastases. Achieving CR, PR or SD is associated with improved survival. Primary tumor treatment with radiotherapy, normal baseline LDH and > 1 M-PHP cycles are associated with improved OS.

Topics: Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Perfusion; Retrospective Studies; Uveal Neoplasms

The aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion.. 54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1-11) treatment sessions were performed with melphalan (92%) or fotemustin (8%). Inflammatory indices were calculated as follows: neutrophils/nl to lymphocytes/nl ratio (NLR), systemic immune-inflammation index ([platelets/nl × neutrophils/nl]/[lymphocytes/nl]; SII), and platelets/nl to lymphocytes/nl ratio (PLR). The cut-off for dichotomization purposes was set at the median (inflammatory indices, hepatic tumor burden) or the upper level of normal. Kaplan Meier analysis was performed for median overall survival (OS) in months, and Cox proportional hazard model for uni(UVA) and multivariate (MVA) hazard ratio (HR, 95%CI) analyses were performed.. Median OS of the study cohort was 7.7 (6.3-10.9) months. In UVA OS was prolonged for low C reactive protein (CRP) (13.5. Pretreatment inflammatory markers (CRP, SII) and AST were independent prognostic survival markers in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. A combination of factors may help to identify patients potentially benefitting from treatment.

Topics: Adult; Aged; Aged, 80 and over; Alanine Transaminase; Antineoplastic Agents; Aspartate Aminotransferases; Biomarkers, Tumor; Blood Platelets; C-Reactive Protein; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Lymphocytes; Male; Melanoma; Melphalan; Middle Aged; Neutrophils; Nitrosourea Compounds; Organophosphorus Compounds; Prognosis; Proportional Hazards Models; Retrospective Studies; Tumor Burden; Uveal Neoplasms

Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT® Delivery System; Delcath Systems Inc, USA) is a novel interventional procedure, which delivers high doses of melphalan directly to the liver in patients with liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. We have previously shown promising efficacy for patients with ocular melanoma (OM) and cholangiocarcinoma (CCA) within our single-center and multi-center experiences. The aim of this study was to analyze the safety and efficacy of CS-PHP after 141 treatments at Hannover Medical School, Germany.. Overall response rates (ORR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median Overall survival (mOS), median progression-free survival (mPFS), and median hepatic PFS (mhPFS) were analyzed using the Kaplan-Meier estimation.. Overall, 60 patients were treated with CS-PHP in the salvage setting from October 2014 until January 2019 at Hannover Medical School with a total of 141 procedures. Half of the patients were patients with hepatic metastases of ocular melanoma (OM) (n = 30), 14 patients had CCA (23.3%), 6 patients had hepatocellular carcinoma (10%), and 10 patients were treated for other secondary liver malignancies (16.7%). In total, ORR and disease stabilization rate were 33.3% and 70.3% (n = 25), respectively. ORR was highest for patients with OM (42.3%), followed by patients with CCA (30.8%). Independent response-associated factors were normal levels of lactate dehydrogenase (odds ratio (OR) 13.7; p = 0.015) and diagnosis with OM (OR 9.3; p = 0.028). Overall, mOS was 9 months, mPFS was 4 months, and mhPFS was 5 months. Patients with OM had the longest mOS, mPFS, and mhPFS with 12, 6, and 6 months, respectively. Adverse events included most frequently significant, but transient, hematologic toxicities (80% of grade 3/4 thrombopenia), less frequently hepatic injury up to liver failure (3.3%) and cardiovascular events including two cases of ischemic insults (5%).. Salvage treatment with CS-PHP is safe and effective particularly in patients OM and CCA. Careful attention should be paid to possible, serious hepatic, and cardiovascular complications.

Topics: Aged; Antineoplastic Agents, Alkylating; Bile Duct Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Cholangiocarcinoma; Female; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Progression-Free Survival; Retrospective Studies; Salvage Therapy; Uveal Neoplasms

To investigate the outcome and safety data of chemosaturation with percutaneous hepatic perfusion (CS-PHP) of melphalan in patients with liver-dominant metastatic uveal melanoma.. This is a HIPAA compliant, IRB approved, retrospective study. A total of 28 CS-PHPs were performed in 16 individual patients (six men and ten women, median age 63.1 years [range 49.1 to 78.7 years], one to six CS-PHP procedures per patient) for treatment of liver-dominant metastatic uveal melanoma between June, 2015 and December, 2018. All patients received cross-sectional imaging at baseline and during follow-up. CS-PHP was performed with the Hepatic CHEMOSAT® Delivery System (Delcath Systems, Inc., NY, USA) facilitating extracorporeal filtration of hepatic blood for melphalan removal. Ideal body weight-adjusted melphalan doses were administered into the hepatic arteries. Serious adverse events (SAE), progression-free survival based on response criteria in solid tumors, and overall survival were noted. Survival data were analyzed using Kaplan-Meier estimates.. Partial response after first CS-PHP was observed in nine patients (60%), stable disease in five patients (33%) and progressive disease in one patient (7%). Median overall survival was 27.4 months (95% CI 4.1 to 35.4 month) after first CS-PHP. Median progression-free survival was 11.1 months after first CS-PHP (95% CI 4.9 to 23.6 months). SAEs were observed in the majority of patients with most SAEs limited to grades one and two. Thirteen SAEs of grades three and four were observed in seven individual patients. No grade five SAE was observed.. CS-PHP is an efficacious and safe treatment for patients presenting with liver-dominant metastatic uveal melanoma.

Topics: Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Liver Circulation; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Metastasis; Uveal Neoplasms

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.. 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.. 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).. M-PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Prognosis; Rare Diseases; Retrospective Studies; Survival Rate; Uveal Neoplasms

Percutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.. Between 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients' life quality was assessed using four-point scale questionnaires.. Of 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6-41.0 months). Median progression-free survival time was 12.4 months (range 0.9-41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients' self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.. PIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

Topics: Adult; Aged; Chemotherapy, Cancer, Regional Perfusion; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Quality of Life; Retrospective Studies; Survival Rate; Uveal Neoplasms

This report describes the outcomes and long-term follow-up data from all isolated hepatic perfusions (IHPs) performed at a single institution in Sweden between the years 1989 and 2013 for patients with isolated uveal melanoma metastases.. A total of 68 patients (median age, 61 years) were treated consecutively at Sahlgrenska University Hospital. Of the 68 patients, 67 % had fewer than 10 tumors. The median diameter of the largest lesion was 2.5 cm. The patients underwent IHP with either melphalan alone or the addition of either tumor necrosis factor-alpha or cisplatin. The response was assessed after 8-12 weeks by computed tomography or magnetic resonance imaging.. The overall response rate was 67 and 20 % of the patients had a complete response. The median times to local and systemic progression were respectively 10 and 14 months. The prognostic factors for time to local recurrence were response and number of tumors. The median survival time was 22 months. The prognostic factors for survival were response, largest tumor diameter, and number of tumors. Five patients (7 %) died within 30 days, and six patients (9 %) experienced major complications (Clavien-Dindo 3/4).. Isolated hepatic perfusion is a treatment option with high response rates and tolerable mortality and morbidity. Whether IHP has a survival benefit compared with other treatment options currently is being investigated in a randomized trial.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Extracorporeal Circulation; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Staging; Prognosis; Survival Rate; Tumor Necrosis Factor-alpha; Uveal Neoplasms; Young Adult

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation. In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.

Topics: Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Extracorporeal Circulation; Heart-Lung Machine; Hepatic Artery; Humans; Liver Neoplasms; Melanoma; Melphalan; Portal Vein; Uveal Neoplasms; Vascular Access Devices

To assess the survival of patients with hepatic uveal melanoma metastases undergoing sequential transarterial hepatic chemoperfusion.. 61 patients (mean age, 60.3 ± 13.8 y) underwent a total of 249 hepatic chemoperfusion procedures (mean: 4 chemoperfusion procedures; range, 1-7 chemoperfusion procedures; standard deviation, 2.3 chemoperfusion procedures). All patients started with melphalan. In the case of progressive disease, melphalan was replaced by a different chemoperfusion agent. 38 patients were treated with melphalan only, 23 patients were treated with a combination of melphalan and other drugs. The median overall survival time was calculated for the overall population and several sub-groups. Differences in the survival rate between the sub-groups were assessed for statistical significance. The complication rate was assessed.. The median overall survival of the entire population was 10 months. The patients in the subgroups with a maximum number of 9 hepatic metastases as well as the patients in the subgroup without extrahepatic metastases at the beginning of therapy survived significantly longer than patients with more than 9 metastases/extrahepatic metastases (p = 0.019, p = 0.008). One patient (0.4%) died from liver failure after initial infusion of melphalan.. Intraarterial sequential hepatic chemoperfusion offers a minimally invasive treatment in patients with hepatic uveal melanoma metastases with good survival times and an acceptable major complication rate.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Humans; Infusions, Intra-Arterial; Liver Failure; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Prognosis; Retrospective Studies; Survival Rate; Uveal Neoplasms