Cyclophosphamide (Cytoxan) is the most versatile and useful of the nitrogen mustards. Preclinical testing showed it to have a favorable therapeutic index and to possess the broadest spectrum of antitumor activity of all alkylating agents. As with the other nitrogen mustards, cyclophosphamide administration results in the formation of cross-links within DNA due to a reaction of the two chloroethyl moieties of cyclophosphamide with adjacent nucleotide bases. Cyclophosphamide must be activated metabolically by microsomal enzymes of the cytochrome P450 system before ioniza-tion of the chloride atoms and formation of the cyclic ethylenimmonium ion can occur. The metabolites phosphoramide mustard and acrolein are thought to be the ultimate active cytotoxic moiety derived from cyclophosphamide.

Cyclophosphamide can be given orally, intramuscularly, or intravenously. The plasma half-life of intact cyclophosphamide is 6.5 hours. Only 10 to 15% of the circulating parent drug is protein bound, whereas 50% of the alkylating metabolites are bound to plasma proteins. Since cyclophosphamide and its metabolites are eliminated primarily by the kidneys, renal failure will greatly prolong their retention.

Cyclophosphamide has a wide spectrum of antitumor activity. In lymphomas, it is frequently used in combination with vincristine and prednisone (CVP [or COP] regimen) or as a substitute for mechlorethamine in the MOPP regimen (C-MOPP). High dosages of intravenously administered cyclophosphamide are often curative in Burkitt's lymphoma, a childhood malignancy with a very fast growth rate. Oral daily dosages are useful for less aggressive tumors, such as nodular lymphomas, myeloma, and chronic leukemias.

Cyclophosphamide is a component of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) and other drug combinations used in the treatment of breast cancer. Cyclophosphamide in combination may produce complete remissions in some patients with ovarian cancer and oat cell (small cell) lung cancer. Other tumors in which beneficial results have been reported include non-oat cell lung cancers, various sarcomas, neu-roblastoma, and carcinomas of the testes, cervix, and bladder. Cyclophosphamide also can be employed as an alternative to azathioprine in suppressing immunological rejection of transplant organs.

Bone marrow suppression that affects white blood cells more than platelets is the major dose-limiting tox-icity. Maximal suppression of blood cell count occurs 10 to 14 days after drug administration; recovery is generally seen 21 to 28 days after injection. Cyclophos-phamide reduces the number of circulating lymphocytes and impairs the function of both humoral and cellular (i.e., B and T cell) aspects of the immune system. Chronic therapy increases the risk of infections. Nausea may occur a few hours after administration. Alopecia is more common than with other mustards.

A toxicity that is unique to cyclophosphamide and ifosfamide is cystitis. Dysuria and decreased urinary frequency are the most common symptoms. Rarely, fibro-sis and a permanently decreased bladder capacity may ensue. The risk of development of carcinoma of the bladder also is increased. Large intravenous doses have resulted in impairment of renal water excretion, hy-ponatremia, and increased urine osmolarity and have been associated with hemorrhagic subendocardial necrosis, arrhythmias, and congestive heart failure. Interstitial pulmonary fibrosis may also result from chronic treatment. Other effects of chronic drug treatment include infertility, amenorrhea, and possible mu-tagenesis and carcinogenesis.

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment