[MOL] FDA approves CYTOPROTECTIVE AGENT for reducing renal toxicity [02615] Medicine On Line


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[MOL] FDA approves CYTOPROTECTIVE AGENT for reducing renal toxicity



Thought this would prove helpful for some of our molers.  Your friend,
lillian


The FDA has approved a new cytoprotective agent -- amifostine (Ethyol/US
Bioscience) -- for reducing the cumulative renal toxicity associated with
repeated cisplatin therapy in patients with advanced ovarian cancer.
Amifostine is an organic thiophosphate prodrug that is rapidly
dephosphorylated in tissues to a pharmacologically-active free thiol. This
thiol compound binds and detoxifies reactive cisplatin metabolites, and
also scavenges free radicals generated in tissues exposed to cisplatin.
Since amifostine reaches a higher concentration in normal tissue relative
to tumor tissue, it is able reduce cisplatin's renal toxicity without
compromising the antitumor efficacy. 

First developed to protect tissues against radiation damage, amifostine has
since proved to be effective for protecting against hematologic toxicity in
patients receiving cisplatin, cyclophosphamide, and/or mitomycin, and to
reduce cisplatin- induced nephrotoxicity, ototoxicity, and neurotoxicity.
In clinical trials, patients treated with amifostine showed a reduction in
neutropenia-related fever and sepsis and spent fewer days in the hospital
and/or on antibacterial therapy, compared with patients who did not receive
amifostine. Moreover, fewer patients discontinued therapy before completing
the scheduled number of treatment cycles. 

Amifostine is given intravenously as a 15-minute infusion of 910 mg/m2
starting 30 minutes prior to cisplatin therapy. The drug is rapidly cleared
from plasma; distribution half-life is less than one minute and elimination
half-life is about 8 minutes. Less than 10% of amifostine remains in the
plasma 6 minutes after administration. The most common side effects are
transient reduction in blood pressure, nausea, vomiting, somnolence, and
sneezing. Less common side effects include flushing, hypocalcemia, and
hiccups. Antiemetics reduce the nausea (pretreatment with dexamethasone or
metoclopramide has no effect on pharmacokinetics). Contraindications
include hypotension, dehydration, hypocalcemia, or sensitivity to
aminothiol compounds or mannitol (the vehicle). 

US Bioscience is continuing Phase II and III trials to evaluate the effects
of ethyol for protecting against radiation damage in patients treated for
tumors of the rectum, cervix, lung and neck. It is also under investigation
for its ability to sensitize a tumor to therapy. It is in trial for use
with Bristol-Myer's taxol, allowing escalation of the dose to more than
twice the dosage currently used in clinical practice. US Bioscience
developed amifostine and owns the patents; Alza has exclusive marketing
rights in the US for five years; Schering-Plough is marketing the drug in
Europe; and Lilly is planning to introduce it in Canada. (Spencer CM, Goa
KL. Drugs 1995;50:1001-1031. Additional information from Alza.) 

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