Craniopharyngioma Medication
- Author: George C Bobustuc, MD; Chief Editor: Tarakad S Ramachandran, MBBS, FRCP(C), FACP more...
Medication Summary
Agents/modalities used in the treatment of craniopharyngioma include (1) bleomycin for local intracystic chemotherapy[27, 28, 29] and (2) radiation therapy applied as external fractionated radiation, stereotactic radiation, or brachytherapy (intracavitary irradiation).[30, 31, 32, 33, 34]
Radiation creates free oxygen ions that damage cellular DNA. The cellular ability to repair DNA is lower for tumor cells than for normal cells and subsequently, with each mitosis, a higher cumulative effect in tumor cells results in apoptosis.
External fractionated radiation
This offers a dual advantage by (1) allotting normal cells more time for repair and (2) amplifying a higher cumulative effect of DNA damage in more rapidly dividing tumor cells.
Radiation, following partial resection, offers excellent long-term results (80% at 20 years). Following partial resection, results of primary irradiation are superior to those with radiation delayed until the time of recurrence. Recurrence is less frequent after imaging-confirmed total resection (10-30% recurrence rate), in which case, radiation should be delayed.
Brachytherapy/radioisotopes
Brachytherapy is recommended for solitary cystic craniopharyngiomas and consists of stereotactic aspiration of cystic content, followed by instillation of beta-emitting isotopes (eg, phosphorus 32, rhenium 186, gold 198, yttrium 90).
Brachytherapy is attractive because about 60% of craniopharyngiomas occur as single, large cysts; early refilling is the rule, requiring intermittent aspiration either by stereotactic puncture or Ommaya reservoir.
Stereotactic radiation
Stereotactic radiation has been used primarily as a first-line for treatment for growing or symptomatic, solid, small craniopharyngiomas (< 25-30 mm in diameter). Stabilization or reduction of the cystic cavity after radiosurgery is achieved in more than 60% of patients.[35]
Stereotactic radiation has also been used for the further treatment of residual solid tumor after brachytherapy.
Intracystic chemotherapy
Intracystic injection of bleomycin[23] and internal irradiation with radioisotopes have been reported to control the tumor cysts in 90-100% of cases.
Antineoplastics, Antibiotic
Class Summary
In combination with other drugs, chemotherapeutic agents are used frequently and systemically against epithelial tumors. In the early 1970s, bleomycin was found to have encouraging results in controlling craniopharyngioma tissue in cultures. Intracavitary bleomycin reduces cyst size and toughens and thickens the cyst wall, thereby facilitating surgical excision of a cyst membrane that otherwise might fragment at the time of open craniotomy. However, reports of intracystic bleomycin use are limited.
Bleomycin
This drug is a mixture of glycopeptides extracted from Streptomyces species. Each molecule has a planar end and an amine end. Different glycopeptides of the bleomycin group differ in their terminal amine moieties. The planar end intercalates with DNA, while the amine end facilitates oxidation of bound ferrous ions to ferric ions, thereby generating free radicals, which subsequently cleave DNA, acting specifically at purine-G-C-pyrimidine sequences.
Bleomycin is not absorbed when given orally. Peak levels are reached in about 30-60 minutes when the drug is given intramuscularly (IM) and are only one third of the levels obtained after intravenous (IV) administration. Approximately 50% of the drug is absorbed systemically after intrapleural or intraperitoneal administration. Systemic absorption after intracavitary administration for craniopharyngioma is not negligible.
The volume of distribution is 20-30L in intracellular and extracellular fluid. Less than 10% is bound to plasma proteins.
Bleomycin has plasma half-life of less than 1 hour and a terminal half-life of 2-4 hours, but it can be as long as 22 hours in patients with renal dysfunction or in patients who have been previously treated with cisplatin.
About 50% of bleomycin is eliminated in urine within 24 hours. Most tissues (with known exceptions being the skin and lungs) contain an enzyme, bleomycin hydrolase (the most active tissues being those of the liver and kidneys), that readily inactivates the drug. Therefore, toxicity is tissue specific, occurring in tissues lacking this enzyme.
Bleomycin is primarily used systemically in combination with other drugs (mostly with cisplatin and vincristine) for the treatment of testicular carcinoma, Hodgkin lymphoma, and non-Hodgkin lymphoma; squamous cell carcinoma of the skin, head and neck, and cervix; and malignant pleural effusions.
The principal mechanisms of resistance include high levels of bleomycin hydrolase, cell mutations altering DNA sequences to prevent intercalation, poor cell accumulation of the drug, and rapid plasma removal. None of these factors plays an important role when bleomycin is administered locally in a residual cyst.
The toxicity of bleomycin is age dependent and cumulative-dose related. Systemic administration mostly causes pulmonary toxicity; this consists of pneumonitis, which can progress to fatal pulmonary fibrosis.
The maximum recommended total cumulative dose of bleomycin for systemic use is 400 U. Unit measurement is based on toxicity to bacteria; 1 U equals approximately 1.7 mg.
When administered systemically, bleomycin does not produce significant bone marrow toxicity. Toxicity with local administration results from systemic contamination (when anaphylactoid reactions, transient fever, nausea, and vomiting could occur) and leakage into surrounding neural tissue.
Fatal outcome has been reported with leakage, due to subsequent diffuse diencephalon and brainstem edema. Others report transient local toxicity with leakage into the surrounding brain reversed by high-dose steroid use.
Contrast CT cystography is required prior to intracavitary administration to ensure cyst wall integrity. When inconclusive, MR cystography with gadopentetate dimeglumine has been advocated.
Radiation
Class Summary
Radiation creates free oxygen ions that damage cellular DNA. Cellular ability to repair DNA is lower for tumor cells than normal cells and subsequently, with each mitosis, a higher cumulative effect in tumor cells results in apoptosis.
External fractionated radiation
Offers dual advantage by (1) allotting normal cells more time for repair and (2) amplifying higher cumulative effect of DNA damage in more rapidly dividing tumor cells.
Radiation, following partial resection, offers excellent long-term results (80% at 20 years). Following partial resection, results of primary irradiation are superior to those with radiation delayed until time of recurrence. Recurrence is less frequent after imaging confirmed total resection (10-30% recurrence rate), in which case radiation should be delayed.
Brachytherapy/radioisotopes
Recommended for solitary cystic craniopharyngiomas and consists of stereotactic aspiration of cystic content, followed by instillation of beta-emitting isotope (eg, phosphorus 32, rhenium 186, gold 198, yttrium 90).
Brachytherapy is attractive because about 60% of craniopharyngiomas occur as single large cysts; early refilling is the rule, requiring intermittent aspiration either by stereotactic puncture or Ommaya reservoir.
Stereotactic radiation has been used for further treatment of residual solid tumor after brachytherapy.
Stereotactic radiation
Has been used primarily as first-line for treatment of growing or symptomatic, solid, small (sized) size craniopharyngioma (< 25-30 mm in diameter). Stabilization or reduction of cystic cavity after radiosurgery achieved in more than 60% of patients.
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