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Transcatheter chemotherapy for malignancies in the brain, head, and neck
Introduction
Intraarterial chemotherapy has long been investigated as a potentially superior treatment modality for tumors of the cervicocephalic, thoracic and abdominopelvic regions, and the limbs. Tumors of the brain, head, and neck have attracted the most attention for several reasons. For brain tumors, particularly high-grade gliomas, the therapeutic benefits from systemic therapy are minimal, even for drugs with recognized activity and a demonstrated dose–response relationship. Theoretically, local infusion should achieve a higher drug concentration in the tumor. This would provide a potentially important palliative option for brain metastases, which are rapidly debilitating and fatal. By the time these tumors are radiologically detectable, there is impairment of the blood–brain barrier, which until then had protected the cancer cells from the action of chemotherapeutic agents administered systemically. Direct intraarterial administration should assist in overcoming drug resistance by ensuring higher concentrations of the drug at the site needed most.
For tumors of the oral cavity, hypopharynx, and larynx, other considerations arise. The early onset of local pain, interference with feeding and speech, and general deterioration call for a treatment that produces the rapid response necessary for the physical and psychological recovery of these patients, who often have advanced disease at presentation. The ability to provide a therapy that could avoid devastating operations would have a major impact on quality of life, particularly because these operations do not improve the prognosis.
Recent percutaneous catheterization techniques, deriving from neuroradiologic practice, have reopened the possibilities for intraarterial therapy. New criteria for preliminary diagnosis and response assessment, and new drug formulations, have revolutionized pharmacokinetic criteria, so higher concentrations can be achieved not only in the area of the tumor but with a significant difference between the tumor and surrounding tissue.
Background of intraarterial chemotherapy for tumors of the head, neck, and brain
Higher local concentrations
Certain characteristics must be taken into consideration when choosing drugs for locoregional treatment by direct intraarterial infusion. Drugs with a particular pharmacokinetic profile, with rapid systemic clearance, are considered to offer an advantage over intravenous administration. Single-drug or combinations of drugs such as carmustine, cisplatin, carboplatin, etoposide, methotrexate, gemcitabine, irinotecan, anthracyclines, and taxanes as macrocomplexes have long been identified as having potential for intraarterial use. Some drugs cross the blood–brain barrier intact but do not reach concentrations that can destroy micrometastases.
The potential pharmacokinetic superiority of intraarterial chemotherapy is manifested at the first pass through the tumor circulation. The positive consequences of the first pass are more evident for some drugs than others, namely, those that have a high extraction fraction by the tumor coupled with rapid systemic clearance through metabolism or excretion.
The blood–brain barrier
Primary or metastatic brain tumors merit a chapter apart because the blood–brain barrier, if intact, does not allow drugs to pass into the brain tissue at high enough concentrations to prevent the infiltration of microscopic metastases. , Intraarterial chemotherapy, when applicable, should not be considered a stand-alone option but should be combined with external radiotherapy to control microscopic disease. When the blood–brain barrier is not intact, the radiopotentiating or radiosensitizing properties of some chemotherapy drugs are potentially predictive of greater efficacy.
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