melphalan and Bile-Duct-Neoplasms

Cholangiocarcinoma (CCA) are the second most common primary liver tumors and carry a dismal prognosis. Chemosaturation with percutaneous hepatic perfusion (PHP) is a palliative, intra-arterial therapeutic approach that provides a high dose chemotherapy of the liver with reduced systemic exposure. Aim of this retrospective, monocentric study was to analyze PHP as a palliative treatment for unresectable CCA. Toxicity, adverse events and complications were classified using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Overall response rate (ORR) and disease control rate (DCR) were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1). Median overall survival (mOS), median progression-free survival (mPFS) and hepatic mPFS (mhPFS) were computed using Kaplan-Meier estimation. In total 17 patients were treated with 42 PHP between 10/2014 and 09/2020. No significant complications occurred during the interventions. mOS was 27.6 (interquartile range (IQR) 16.5-37) months from first diagnosis and 9.9 (IQR 3.8-21) months from first PHP. mPFS was 4 (IQR 2-7) and mhPFS was 4 (IQR 3-10) months. ORR was 25% and DCR 75%. Significant, but transient hematotoxicity was frequent with grade 3/4 thrombopenia after 50%, leukopenia after 26% and anaemia after 21% of the interventions. An increase of transaminases (AST increase after 21% and ALT increase after 14% of the PHP) developed more often than a deterioration of the liver synthesis capacity. Salvage treatment with PHP has the potential to prolong life in selected patients with unresectable, refractory cholangiocarcinoma. The interventional procedure is safe. Post-interventional toxicity is frequent but manageable.

Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Chemotherapy, Cancer, Regional Perfusion; Cholangiocarcinoma; Humans; Liver Neoplasms; Melphalan; Palliative Care; Perfusion; Retrospective Studies

Chemosaturation (CS; CHEMOSAT®, Delcath Systems Inc.) temporarily administers melphalan into the liver by percutaneous hepatic perfusion (PHP). CS-PHP can effectively control growth in liver tumors, but efficacy and tolerability of sequential treatments are unclear. We analyzed outcomes of sequential CS-PHP treatment. Patients with either unresectable intrahepatic metastases of ocular melanoma (OM, n = 9), cholangiocarcinoma (CCA, n = 3), or hepatocellular carcinoma (HCC, n = 1) were recruited retrospectively. Response was assessed by tomography imaging. Ten patients (mean age 60 years) with more than one CS-PHP treatment were included. CS-PHP was administered 2-6 times in the OM patients, 3 times in the CCA, and the HCC patient received 6 treatments. Overall response rate (ORR) to CS-PHP was 80%, and stable disease was achieved in one patient. Median hepatic progression-free survival (hPFS) was 336 days (range 0-354) for OM, 251 days for the CCA patient, and 256 days for the HCC patient. At the end of observation (153-701 days after first CS-PHP), 6/10 patients were still alive (5/9 with OM, 0 with CCA, and 1 with HCC). Death cases were not related to CS-PHP. Adverse events were mostly hematologic, grade I-IV, and self-resolving. The liver function was not deteriorated by CS-PHP. We conclude that repeated CS-PHP treatments were effective and well tolerated in the long term.

Topics: Antineoplastic Agents, Alkylating; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Chemotherapy, Cancer, Regional Perfusion; Humans; Liver Neoplasms; Melphalan; Middle Aged; Perfusion; Retrospective Studies

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

Cholangiocarcinoma is the second most common primary liver tumour with a poor overall prognosis. Percutaneous hepatic perfusion (PHP) is a directed therapy for primary and secondary liver malignancies, and its efficacy and safety have been shown in different entities. The purpose of this study was to prove the safety and efficacy of PHP in patients with unresectable intrahepatic cholangiocarcinoma (iCCA).. We retrospectively reviewed data from 15 patients with unresectable iCCA treated with PHP in nine different hospitals throughout Europe. Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumours (RECIST1.1). Overall survival (OS), progression-free survival (PFS) and hepatic PFS (hPFS) were analysed using the Kaplan-Meier estimation. Adverse events (AEs) and toxicity were evaluated.. Fifteen patients were treated with 26 PHPs. ORR was 20%, disease control was achieved in 53% after the first PHP. Median OS was 26.9 months from initial diagnosis and 7.6 months from first PHP. Median PFS and hPFS were 122 and 131 days, respectively. Patients with liver-only disease had a significantly longer median OS compared to patients with locoregional lymph node metastases (12.9 vs. 4.8 months, respectively; p < 0.01). Haematological toxicity was common, but manageable. No AEs of grade 3 or 4 occurred during the procedures.. PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with iCCA, especially in non-metastatic disease.. • Percutaneous hepatic perfusion (PHP) offers an additional locoregional therapy strategy for the treatment of unresectable primary or secondary intrahepatic malignancies. • PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with intrahepatic cholangiocarcinoma (iCCA), especially in non-metastatic disease. • Side effects seem to be tolerable and comparable to other systemic or local treatment strategies.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Bile Duct Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Cholangiocarcinoma; Europe; Female; Humans; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Neoplasms, Second Primary; Retrospective Studies; Survival Analysis

The technique of right hepatic trisegmentectomy has been standardized for large tumors that involve the right lobe and extend into the medial segment of the left lobe. However, these tumors are deemed unresectable if they encroach across the falciform ligament into the left lateral segment. We report the technique of extended right trisegmentectomy in a patient with a large intrahepatic cholangiocarcinoma that involved the right lobe of the liver and extended into the medial and lateral segments of the left lobe. The resection was performed by using total hepatic vascular isolation and in situ hypothermic perfusion with modified histidine-tryptophan-ketoglutarate (HTK) solution into the left lateral segment. The biliary enteric anastomosis was constructed using a double hepaticojejunostomy to Segments II and III bile ducts. The procedure allowed safe parenchymal dissection with preservation of the blood supply to Segments II and III. Furthermore, in situ hypothermic perfusion protected the remnant liver from the deleterious effects of warm ischemia during parenchymal dissection and facilitated postoperative recovery. To the best of our knowledge, this is the first report of extended right trisegmentectomy for the treatment of intrahepatic cholangiocarcinoma in the Western literature.

Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biliary Tract Surgical Procedures; Cholangiocarcinoma; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Glucose; Hepatectomy; Humans; Hypothermia, Induced; Immunoglobulin G; Jejunostomy; Mannitol; Melphalan; Middle Aged; Perfusion; Potassium Chloride; Procaine; Tomography, Spiral Computed; Yttrium Radioisotopes

Increasing the drug concentration in tumors may produce massive tumoral response. By using a variety of hepatic vascular isolation techniques, high concentrations of chemotherapeutic drugs may be achieved in the hepatic vascular bed.. Complete percutaneous isolated hepatic perfusion (IHP) is feasible and safe.. Case series.. The hepatobiliary unit of a university hospital.. Ten patients with irresectable and chemoresistant hepatic tumors were eligible for study participation; 4 patients with hepatic metastases of breast cancer, gastric cancer, colorectal cancer, and cholangiocarcinoma were included.. Patients received 3 successive courses of chemotherapy by IHP. The first course was given at laparotomy, and the next 2 courses were given percutaneously. The interval between courses was 3 to 6 weeks. Each course involved IHP of the liver for 15 to 30 minutes, without oxygenation, with 1 to 3 boluses of melphalan (15 mg).. Morbidity and mortality.. Ten IHPs were performed (4 at laparotomy and 6 percutaneously). Concentrations of melphalan in the extracorporeal circulation were 10 times higher than those in the systemic circulation. Percutaneous IHPs had more leakage than those at laparotomy. However, hepatotoxicity was minimized. One patient experienced hepatic artery thrombosis, and 3 had severe neutropenia. Minor complications included ascites and pleural effusion. No deaths were observed 2 months after the last IHP. One partial response was observed (hepatic metastases of breast cancer).. Percutaneous IHP for intensive chemotherapy is less aggressive and less hepatotoxic than IHP at laparotomy and may be iterative.

Topics: Adenocarcinoma; Antineoplastic Agents; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Breast Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Cholangiocarcinoma; Colorectal Neoplasms; Fatal Outcome; Female; Humans; Laparotomy; Liver Neoplasms; Male; Melphalan; Middle Aged; Radiography, Interventional; Stomach Neoplasms