eMedicine Specialties > Neurology > Neuro-oncology

CNS Melanoma: Treatment & Medication

Author: Sheila Au, MD, Clinical Assistant Professor, Department of Dermatology, University of British Columbia, Canada
Coauthor(s): Jason K Rivers, MD, FRCP(C), Clinical Professor, Department of Dermatology and Skin Science, University of British Columbia, Canada; Consulting Staff, Pacific Dermaesthetics; Frederick M Vincent, Sr, MD, Clinical Professor, Department of Neurology and Ophthalmology, Michigan State University Colleges of Human and Osteopathic Medicine
Contributor Information and Disclosures

Updated: Sep 5, 2006

Treatment

Medical Care

Melanoma that metastasizes to the CNS is incurable. Treatment is aimed at tumor debulking, symptom relief, and palliation. The patient usually can be monitored on an outpatient basis. Inpatient care may be required for patients who require evaluation, surgery, or palliative radiotherapy. The use of steroids provides symptom relief by decreasing cerebral edema.

Treatment options are based on the number and size of CNS lesions and the presence of extracranial disease. Several comprehensive reviews of the treatment of CNS melanoma metastases are available (Bafaloukos, 2004; Tarhini, 2004; Douglas, 2002; Wong, 2004). A brief summary of these literature reviews follows.

  • Whole brain radiation therapy
    • Radiotherapy is effective for palliation. Improvement in neurological deficits post–whole brain radiation therapy (WBRT) is well documented.
    • WBRT can be used for solitary and multiple brain metastases.
    • No increase in overall survival is seen if used alone.
    • Increased overall survival may be seen if WBRT is used in combination with tumor resection.
  • Stereotactic radiosurgery
    • Stereotactic radiosurgery (SRS) involves high doses of radiation delivered to the tumor in one fraction, in a single session, with relative sparing of surrounding tissues.
    • SRS is used for single or multiple CNS metastases; patients with single lesions have a better outcome.
    • One of the main advantages of SRS is the treatment of surgically inaccessible metastases.
    • SRS (with or without WBRT) can provide effective local control comparable to surgery plus WBRT.
    • Rare side effects of SRS include CNS radiation necrosis that requires surgery or systemic steroids. This complication may be seen in 5-10% of patients receiving SRS.
    • Local tumor control rates with SRS are quoted as 76-97% in the literature.
    • Median survival with SRS ranges from 4-7 months.

Surgical Care

  • Surgery is recommended for solitary brain metastases. The patient should have controllable systemic disease to be considered for surgery. However, surgical resection is still a viable option for symptomatic patients with one or more systemic metastases.
  • Addition of postoperative WBRT is considered by some to be more effective than surgery alone in local tumor control, as microscopic foci are likely to exist even after complete tumor resection.
  • Surgery can significantly improve neurological signs and symptoms; however, a proportion of patients undergoing brain surgery for melanoma can have postoperative worsening of their neurological symptoms.
  • Limitations of surgery include the inaccessibility of deep-seated or multifocal CNS lesions. Some patients may be too ill to tolerate brain surgery.
  • The effect of surgery on median survival is controversial.

Consultations

A multidisciplinary team consisting of a neurologist, neurosurgeon, medical oncologist, dermatologist, and radiation oncologist should manage complex cases of metastatic melanoma.

Medication

The goals of pharmacotherapy are to induce remission, prevent complications, and reduce morbidity. Chemotherapy in patients with CNS metastases is recommended for patients who are not surgical candidates or have multiple metastases.

Fotemustine is a phosphoalanine-modified nitrosourea. It effectively crosses the blood-brain barrier. Main adverse effects are leukopenia and thrombocytopenia. Overall response rates of 12% have been found in phase 2 European Organization for Research and Treatment of Cancer (EORTC) Melanoma Cooperative Group trials. These were partial responses only. Unfortunately, the use of fotemustine is limited by its marked myelosuppressive properties.

Temozolomide is an oral alkylating agent. It effectively crosses the blood-brain barrier and is used to treat some primary brain tumors. Major adverse effects of temozolomide are nausea, vomiting, and myelotoxicity (thrombocytopenia and lymphopenia). Temozolomide has been studied as a single agent and in combination with other modalities. Temozolomide is at least as effective as dacarbazine (DTIC), the drug used historically for metastatic melanoma. It has the advantage of oral administration, and it demonstrates superior blood-brain barrier penetration.

In a recent phase II trial, overall response rates of 40% (partial responses and stabilizing disease only) were found. Temozolomide was used as single agent chemotherapy in 21 patients with CNS melanoma, in a more frequent dosing regimen than usual (75 mg/m2/d for 6 out of every 10 wk).

In an attempt to correct the profound lymphopenia seen in patients taking temozolomide, the drug was used in combination with GM-CSF, low-dose IL-2, and interferon alpha in a phase I/II study. This regimen had a favorable effect upon myelotoxicity, with cytopenias that were manageable on an outpatient basis.

Temozolomide has also been studied with a number of other modalities such as docetaxel, cisplatin, WBRT, and thalidomide, with variable results.

Summary of treatment options for metastatic melanoma to the brain is as follows:

  • For 1-3 lesions: Consider surgery plus or minus WBRT, or SRS plus or minus WBRT.
  • For large or multiple CNS metastases: Consider WBRT or chemotherapy.

Chemotherapy and hormonal therapy

These agents inhibit cell growth and proliferation.


Dacarbazine (DTIC-Dome)

The only FDA-approved chemotherapeutic agent for melanoma; exact mechanism of action unknown. Inhibits DNA, RNA, and protein synthesis. Inhibits cell replication throughout all phases of cell cycle.

Adult

2-4.5 mg/kg/d IV for 10 d; may be repeated at 3-wk intervals

Pediatric

Not established

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in bone marrow suppression, renal and/or hepatic impairment; avoid extravasation


Temozolomide (Temodar)

Oral alkylating agent converted to MTIC at physiologic pH; 100% bioavailable; approximately 35% crosses the blood-brain barrier.

Adult

Adjust dose according to nadir neutrophil and platelet counts from previous cycle and at time of initiating next cycle
Concomitant phase: 75 mg/m2/d PO for 42-49 d with concomitant radiotherapy
Maintenance cycle 1: 150 mg/m2/d PO for 5 d followed by 23 d without treatment; initiated 4 wk following concomitant phase completion
Maintenance cycles 2-6: 200 mg/m2/d PO for 5 d; escalate dose from phase 1 only if blood count stable

Pediatric

Not established

Documented hypersensitivity to temozolomide or DTIC, since each drug is metabolized to MTIC

Pregnancy

D - Unsafe in pregnancy

Precautions

Causes bone marrow suppression resulting in thrombocytopenia, anemia, and leukopenia (check blood counts weekly during concomitant phase, then at day 1 and 21 of each cycle); common adverse effects include nausea, vomiting, and alopecia; it is not known if the drug is excreted in breast milk and because of potential serious adverse effects in infants, breastfeeding should be discontinued; PCP prophylaxis required during concomitant phase, continue if lymphocytopenia develops

More on CNS Melanoma

Overview: CNS Melanoma
Differential Diagnoses & Workup: CNS Melanoma
Treatment & Medication: CNS Melanoma
Follow-up: CNS Melanoma
References
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Further Reading

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Keywords

intracerebral melanoma, intracerebral metastatic melanoma, metastatic melanoma, central nervous system melanoma, central nervous system cancer, CNS cancer, brain cancer, brain melanoma

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Contributor Information and Disclosures

Author

Sheila Au, MD, Clinical Assistant Professor, Department of Dermatology, University of British Columbia, Canada
Sheila Au, MD is a member of the following medical societies: Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Jason K Rivers, MD, FRCP(C), Clinical Professor, Department of Dermatology and Skin Science, University of British Columbia, Canada; Consulting Staff, Pacific Dermaesthetics
Jason K Rivers, MD, FRCP(C) is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, British Columbia Medical Association, Canadian Dermatology Association, Canadian Medical Association, Pacific Dermatologic Association, Royal College of Physicians and Surgeons of Canada, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Frederick M Vincent, Sr, MD, Clinical Professor, Department of Neurology and Ophthalmology, Michigan State University Colleges of Human and Osteopathic Medicine
Frederick M Vincent, Sr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Forensic Examiners, American College of Legal Medicine, American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Clinical Oncology, American Society of Neurorehabilitation, and Michigan State Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Norman C Reynolds Jr, MD, Professor, Department of Neurology, Medical College of Wisconsin
Norman C Reynolds Jr, MD is a member of the following medical societies: American Academy of Neurology, American Chemical Society, American Clinical Neurophysiology Society, Association of Military Surgeons of the US, Movement Disorders Society, Sigma Xi, and Society for Neuroscience
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Jorge Kattah, MD, Head, Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria
Jorge Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, and New York Academy of Sciences
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

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