Chemoembolization of the hepatic artery with BCNU for metastatic uveal melanoma: results of a phase II study

Abstract

Uveal melanoma is the most common primary intraocular malignancy in adults and the liver is the most common site for systemic metastases. We conducted a phase II clinical trial for patients with hepatic metastases from uveal melanoma using chemoembolization of the hepatic artery with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) dissolved in ethiodized oil. Gelatin sponge particles were used as a transiently occlusive agent. The responses in hepatic metastases, overall survival, time to progression and side-effects related to chemoembolization were evaluated. Thirty patients were enrolled. Twenty-four patients completed at least one treatment to all targeted liver metastases and were evaluable for hepatic response. Eighteen of these 24 patients experienced regression or stabilization of hepatic metastases for at least 6 weeks (one complete response in hepatic metastases; four partial responses; 13 stable disease). One of the 13 patients with stable disease was rendered free of disease by surgical removal of metastases after chemoembolization (surgical complete response). The overall response rates (complete and partial responses) for intention-to-treat patients and for patients who were evaluable for response were 16.7 and 20.4%, respectively. The median overall survival of the entire intention-to-treat group of patients was 5.2 months (range, 0.1-27.6 months), for patients with complete or partial response in hepatic metastases 21.9 months (range, 7.4-27.6 months), for patients with stable disease 8.7 months (range, 2.9-14.4 months) and for patients with progressive disease 3.3 months (range, 1.6-5.6 months). Importantly, 13 of the 18 patients who achieved complete response, partial response or stable disease subsequently developed progression of extrahepatic metastases with control of hepatic metastases. Chemoembolization with BCNU is a useful palliative treatment for the control of hepatic metastases in uveal melanoma patients. However, progression in extrahepatic sites after stabilization of hepatic metastases requires further improvement in the therapeutic approach to this disease.

Management of Uveal Melanoma: A Consensus-Based Provincial Clinical Practice Guideline

“…Furthermore, most systemic therapies for metastatic uveal melanoma (largely modelled after therapies for cutaneous melanoma) have failed to demonstrate clinical efficacy in phase ii trials [65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] . However, immunotherapies, including the anti-ctla4 antibody ipilimumab, have shown some success in retrospective and expanded-access studies [82][83][84][85][86][87] .…”

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

“…Systematic search of the literature de-novo: [549][550][551][552][553][554][555][556][557][558][559][560][561][562][563][564][565][566] Strength of consensus: 100 %…”

“…Applied cytostatic agents included cisplatin, fotemustine mitomycin C, and BCNU [550,553,554,558,561,562,565,566]. In the largest trial with 42 cutaneous melanoma patients with suffering from liver metastases, Ahar et al were able to show objective response rates (complete and partial response) of 13.9 % and median overall survival of 7.69 months.…”

Uveal Melanoma: A Review of the Literature

“…Most studies investigating hepatic arterial embolization utilize the transarterial chemoembolization (TACE) procedure and various chemotherapeutic agents (e.g., fotemustine, cisplantin, and 1,3-bis(2-chloroethyl)-1-nitrosourea) followed by the administration of an embolizing agent [114][115][116][117][118]. In these studies response rates ranged from 0% to 39%, and median overall survival ranged from 5.0 to 8.9 months.…”

“…In these studies response rates ranged from 0% to 39%, and median overall survival ranged from 5.0 to 8.9 months. Key prognostic factors in TACE treatment include the degree of liver involvement (with more extensive liver involvement being associated with poorer overall median survival durations), baseline lactate dehydrogenase level, and the number of additional visceral sites involved [115][116][117]. In an effort to incite a systemic immune response against tumor cells and improve patient outcomes, Sato et al performed transaterial embolization with granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with metastatic ocular melanoma limited to the liver [114].…”