Melphalan in Regional Chemotherapy for Locally Recurrent Metastatic Melanoma

Abstract

In-transit metastases occur in approximately 3% of melanoma patients, can be very symptomatic and survival in this group may be prolonged. Regional chemotherapy with melphalan delivered by isolated limb perfusion (ILP) or isolated limb infusion (ILI) are effective treatment options which are generally well tolerated. ILI is a less invasive and simpler alternative to ILP. ILI is tolerated better than ILP, though is probably less effective. Complete response rates are 45- 69% for ILP and 23-44% for ILI. The limb is often warmed to lower temperatures in ILI compared to ILP and the limb becomes progressively more hypoxic and acidotic during ILI, each of these parameters potentially having an effect on outcome. ILP & ILI are used primarily as palliative options when excision of in-transit metastases is unfeasible but can be used as an adjunctive procedure to surgery, for other tumour types such as merkel cell carcinoma, and can be repeated if indicated. For ILI correction of melphalan dose for ideal body weight has been shown to substantially decrease the rates of severe local toxicity while maintaining complete response rates, but overall response rate is reduced. Combination treatment with tumour necrosis factor α has been used with variable outcomes and new combinations with buthionine sulfoximine and ADH-1 are being investigated.

Silicon‐Free SuFEx Reactions of Sulfonimidoyl Fluorides: Scope, Enantioselectivity, and Mechanism

“…Further motive is provided by the usefulness of the product, as the resulting sulfoximine group, and structural variations thereof, can express significant medicinal activity . For example, buthionine sulfoximine is a potential adjunct with chemotherapy in the treatment of metastatic melanoma, while atuveciclib is the first potent and highly selective PTEFb/CDK9 inhibitor to enter clinical trials for the treatment of cancer (Figure b) …”

Hydroquinone Exhibits In Vitro and In Vivo Anti-Cancer Activity in Cancer Cells and Mice

“…Since sulfhydryl group (SH-) of cysteine in target proteins (Akt and Src) plays a critical role in mediating pharmacological activity of HQ [ 20 , 27 ], it was assumed that cellular level of reduced glutathione (GSH) could be important in controlling HQ’s activity. BSO was reported to block cellular resistance to chemotherapy by inhibiting γ-glutamylcysteine synthetase, a key enzyme in glutathione biosynthesis which can regulate the level of glutathione, and used as an adjunct with chemotherapy in the treatment of cancer [ 28 , 29 , 30 ]. Therefore, we employed BSO to test our assumption as to whether combination can increase the anti-proliferative activity of HQ.…”

The Role of Regional Therapies for in-Transit Melanoma in the Era of Improved Systemic Options

“…High dose, limb directed chemotherapy results in a greater treatment effect, while simultaneously minimizing systemic toxicity. The most commonly used chemotherapeutic agent in regional therapy is melphalan, a type of alkylating agent [ 79 ]. The dosage of melphalan for both ILP and ILI is volume based (7.5 mg/L lower extremity limb volume, 10 mg/L upper extremity limb volume) with ideal body weight correction for ILI.…”