Cytoxan

say: sigh -TOX - en

Also often called cyclophosphamide, say cyclo-FOSS-fa-mid, although it is also acceptable to say cyclo-FOSS-fa-mide, with a long "eye" sound in the last syllable.

The CA names for cytoxan are N,N-bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide; 2-[bis(2-chloroethyl)amino]tetrahydro-2H1,3,2-oxazophosphorine 2-oxide. The CA registry number is 50-18-0 (or 6055-19-2 for the hydrated form). According to the Merck Index, cytoxan has been used in the treatment of rheumatoid arthritis, multiple sclerosis, leukemias, and as a defleecing agent for sheep (!). The LD50 orally in mice, rats is 350, 94 mg/kg. Cytoxan is both a carcinogen and a tetrotogen (causes birth defects). It is an antineoplastic. For information on carcinogenicity, go here and then scroll down to "cyclophosphamide" to download a pdf file on this chemical.

Cytoxan is an alkylating agent that forms covalent bonds with the building blocks of DNA. Specifically, it causes cross-links in the DNA. The DNA double helical structure is unable to unwind, cell division does not occur, and the cells die. From what I can find, it is not cytoxan itself that is the alkylating agent, but a different chemical, or an intermediate, that forms when cytoxan is broken down in the body. I found a paper on the Web in which researchers are studying these intermediates in the hopes of finding an intermediate that will kill cancer cells with less side effects. Another paper discusses long term follow up of cytoxan combined with cisplatin in the treatment of ovarian cancer (the original paper used to be on the web but the link is no longer working 1/04). They felt that the two worked particularly well together because they each damage the DNA with a different mechanism, cytoxan with cross-linking and cisplatin with kinking. I haven't heard of these two being used together in leukemia, yet.

Cytoxan is one of the nastier chemo drugs. Side effects that should be reported immediately to your onco doc are:

Side effects that should be reported soon, but not immediately are:

Darkening of skin and fingernails, headache, loss of appetite, and nausea or vomiting and loss of hair are quite likely and, while bothersome, are not life threatening. If your child vomits shortly after a dose, check with the oncodoc. The side effects may persist after treatment discontinues, talk to your oncodoc about them. Especially watch for blood in the urine. A site on the Web about AIDS related drugs called the Access Project lists the above side effects AND also heart inflammation. It also says not to use it with phenobarbital, rifampin, allopurinol, cardiotoxicity may be additive with other cardiotoxic agents such as doxorubicin.

Cytoxan is given over a half hour period through IV injection. It is very important to drink a lot of water before the dose, otherwise the docs won't even give it until after IV hydration. After the dose, the urine is monitored hourly for 4 hours, to make sure the drug is being processed out of the body. After and even during the dose, the patient should drink as much water or juice as possible: for an adult, 3 quarts of liquid in a day. Do not get any immunizations without the doctor's approval for several weeks after the treatment: this goes both for the patient and for household members.

For the sheet we were given at the hospital, go here.


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