General Toxicological Properties of Anticancer Drugs

GENERAL TOXICOLOGICAL PROPERTIES OF ANTICANCER DRUGS

Most of the drugs used in cancer treatment have a thera-peutic index that approaches unity, exerting toxic effects on both normal and tumor tissues even at optimal dosages. This lack of selective toxicity is the major limit-ing factor in the chemotherapy of cancer. Rapidly pro-liferating normal tissues, such as bone marrow, gastroin-testinal tract, and hair follicles, are the major sites of acute toxicity of these agents. In addition, chronic and cumulative toxicities may occur. The most commonly encountered toxicities of antineoplastic agents are de-scribed in the following section;.

Bone Marrow Toxicity

Chemotherapy may result in the destruction of actively proliferating hematopoietic precursor cells. White blood cell and platelet counts may in turn be decreased, resulting in an increased incidence of life-threatening infections and hemorrhage. Maximum toxicity usually is observed 10 to 14 days after initiation of drug treat-ment, with recovery by 21 to 28 days. In contrast, the ni-trosourea drugs exhibit hematological toxicity that is delayed until 4 to 6 weeks after beginning treatment.

The risk of serious infections has been shown to in-crease greatly when the peripheral blood granulocyte count falls below 1000 cells/mm³.A chronic bone marrow toxicity or hypoplastic state may develop after long-term treatment with nitrosoureas, other alkylating agents, and mitomycin C. Thus, patients frequently will require a pro-gressive reduction in the dosages of myelosuppressive drugs when they are undergoing long-term therapy, since such treatment may result in chronic pancytopenia.

Gastrointestinal Tract Toxicity

The nausea and vomiting frequently observed after an-ticancer drug administration are actually thought to be caused by a stimulation of the vomiting center or chemoreceptor trigger zone in the central nervous sys-tem (CNS) rather than by a direct gastrointestinal ef-fect. These symptoms are ameliorated by treatment with phenothiazines and other centrally acting antiemetics. Commonly, nausea begins 4 to 6 hours after treatment and lasts 1 or 2 days. Although this symptom is distressing to patients, it is rarely severe enough to re-quire cessation of therapy. Anorexia and alterations in taste perception also may be associated with chemo-therapy.

The serotonin antagonist ondansetron (Zofran) has proved effective in the prevention of nausea and vomit-ing due to chemotherapy.

Damage to the normally proliferating mucosa of the gastrointestinal tract may produce stomatitis, dyspha-gia, and diarrhea several days after treatment. Oral ul-cerations, esophagitis, and proctitis may cause pain and bleeding.

Hair Follicle Toxicity

Most anticancer drugs damage hair follicles and pro-duce partial or complete alopecia. Patients should be warned of this reaction, especially if paclitaxel, cy-clophosphamide, doxorubicin, vincristine, methotrex-ate, or dactinomycin is used. Hair usually regrows nor-mally after completion of chemotherapy.