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Systematic review of medical treatment in melanoma: current status and future prospects.

ABSTRACT: The incidence of melanoma is increasing worldwide, and the prognosis for patients with high-risk or advanced metastatic melanoma remains poor despite advances in the field. Standard treatment for patients with thick (?2.0 mm) primary melanoma with or without regional metastases to lymph nodes is surgery followed by adjuvant therapy or clinical trial enrollment. Adjuvant therapy with interferon-? and cancer vaccines is discussed in detail. Patients who progress to stage IV metastatic melanoma have a median survival of ?1 year. Standard treatment with chemotherapy yields low response rates, of which few are durable. Cytokine therapy with IL-2 achieves durable benefits in a greater fraction, but it is accompanied by severe toxicities that require the patient to be hospitalized for support during treatment. A systematic literature review of treatments for advanced, metastatic disease was conducted to present the success of current treatments and the promise of those still in clinical development that may yield incremental improvements in the treatment of advanced, metastatic melanoma.

SUBMITTER: Garbe C

PROVIDER: S-EPMC3228046 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Systematic review of medical treatment in melanoma: current status and future prospects.

Garbe Claus C Eigentler Thomas K TK Keilholz Ulrich U Hauschild Axel A Kirkwood John M JM

The oncologist 20110106 1

The incidence of melanoma is increasing worldwide, and the prognosis for patients with high-risk or advanced metastatic melanoma remains poor despite advances in the field. Standard treatment for patients with thick (≥2.0 mm) primary melanoma with or without regional metastases to lymph nodes is surgery followed by adjuvant therapy or clinical trial enrollment. Adjuvant therapy with interferon-α and cancer vaccines is discussed in detail. Patients who progress to stage IV metastatic melanoma hav ...[more]

PMID: 21212434

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Project description:Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from ?9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fat-containing meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 2C19, which it strongly inhibits. A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies' approval was granted based on four pivotal double-blind, placebo-controlled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint (reduction in monthly seizure frequency) was met by both CBD doses. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy. The interaction between CBD and clobazam, likely due to CYP2C19 inhibition, might contribute to some AEs, especially somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the propyl analogue of CBD, showed anti-convulsant properties in pre-clinical studies, but a plant-derived, purified proprietary formulation of CBDV recently failed the Phase II RCT in patients with uncontrolled focal seizures.

Dataset Information

Systematic review of medical treatment in melanoma: current status and future prospects.

Publications

Systematic review of medical treatment in melanoma: current status and future prospects.

Similar Datasets

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