Leptomeningeal Carcinomatosis Medication

  • Author: R Andrew Sewell, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA   more...
 
Updated: Feb 3, 2012
 

Medication Summary

Chemotherapy is best administered intrathecally so that chemotherapeutic agents, which are usually hydrophilic, do not encounter the blood-brain barrier and easily reach tumor cells in the CSF or leptomeninges. The preferred route of administration is through an implanted subcutaneous reservoir (eg, Rickham or Ommaya reservoir) and ventricular catheter rather than LP, for 4 reasons. First, intraventricular injection through an Ommaya reservoir is easy and ensures entry into the CSF. Second, when injected into the ventricle, the drug follows normal CSF flow and thus reaches all parts of the CSF space. Third, repetitive LPs are arduous and painful for the patient. Fourth, about 10-15% of LPs do not deliver all of the drug intended to reach the subarachnoid space.

CSF flow abnormalities are common in patients with increased ICP and hydrocephalus, and 70% of patients with LC have ventricular outlet obstructions, abnormal spinal canal flow, or impaired flow over the cortical convexities, but these can be reversed with local radiation therapy. A CSF-flow study is recommended for all patients at the initiation of intrathecal chemotherapy, and such therapy should be deferred if an obstruction is noted. Systemic therapy can be useful if the blood-brain barrier already has been disrupted or if the chemotherapeutic agent is lipid soluble.

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Chemotherapeutic agents

Class Summary

These agents inhibit cell growth and proliferation.

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Methotrexate (Folex PFS, Rheumatrex)

 

Mainstay of treatment. Because meningeal infiltration interferes with drug clearance, CSF concentrations can be unpredictable. Monitor and maintain concentration near 10-6 M, and coadminister with folinic acid and hydrocortisone if necessary.

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Cytarabine (Cytosar-U)

 

Second-line agent used if MTX not tolerated or ineffective. Not effective for solid tumors but useful in leukemic and lymphomatous meningitis. Half-life longer in CSF than serum. Sustained-release form available in United States; extends half-life to >140 h.

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Thiotepa

 

Third-line agent, cleared from CSF within minutes and has survival curves similar to those of MTX with less neurologic toxicity (most common being transient limb paresthesias). Unlike MTX, no antidote for resulting myelosuppression is available. Causes cross-linking of DNA strands, inhibiting of RNA, DNA, and protein synthesis and thus cell proliferation.

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Contributor Information and Disclosures
Author

R Andrew Sewell, MD  Associate Research Scientist in Psychiatry and Mental Illness Research, Education,Veterans Affairs Connecticut Health Care System, Yale University School of Medicine

R Andrew Sewell, MD is a member of the following medical societies: American Academy of Neurology, American Headache Society, American Pain Society, and American Psychiatric Association

Disclosure: Nothing to disclose.

Coauthor(s)

Lawrence D Recht, MD  Professor of Neurology and Neurosurgery, Department of Neurology and Clinical Neurosciences, Stanford University Medical School

Lawrence D Recht, MD is a member of the following medical societies: American Academy of Neurology, American Association for Cancer Research, American Neurological Association, and Society for Neuroscience

Disclosure: Nothing to disclose.

Specialty Editor Board

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 College of Forensic Examiners, American College of Legal Medicine, American College of Physicians, and Michigan State Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jorge C Kattah, MD  Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, and New York Academy of Sciences

Disclosure: Biogen Honoraria Consulting; Bayer Corporation Honoraria Consulting

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

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: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

Stephen A Berman, MD, PhD, MBA  Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

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