[MOL] Part 5/Chemo Toxicity/Hypersensitivity,Fertility,Cardiac, [00961] Medicine On Line

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[MOL] Part 5/Chemo Toxicity/Hypersensitivity,Fertility,Cardiac,

XII.  Hypersensitivity Reactions from Chemotherapy
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Chemotherapy can cause some type of allergic reactions, better classified as hypersensitivity reactions (HSR).

Drug Type of Reaction and Treatment Frequency Premedication
Paclitaxel (Taxol) Type I. Severe HSRs include shortness of breath, wheezing, hives and itching, and low blood pressure, which occur within minutes after treatment usually after the 1st or 2nd dose. Most reactions resolve completely after stopping treatment and occasionally after treatment with diphenhydramine, fluids and dexamethasone. The drug may be restarted as a slower infusion rate and gradually increased after given premedications. 2-3% with premedication 1. Dexamethasone 20 mg orally 12 and 6 hours before treatment and 20 mg IV just before administration 2. Ranitidine 150 mg or cimetidine 300 mg IV 30 minutes prior to administration. 3. Diphenhyramine 50 mg orally and IV in the same schedule as dexamethasone.
Docetaxel (Taxotere) Type I. Most HSRs are minor and characterized by flushing, chest tightness, and low back pain. A major HSR is characterized by shortness of breath, wheezing, and low blood pressure usually occurring in the 1st 2 cycles and within minutes of starting the infusion. Discontinue treatment with docetaxel and administer diphenhydramine 50 mg IV and dexamethasone 10 mg IV. After resolution of symptoms, docetaxel may be restarted at a slower infusion rate. 2-3% with premedication 1. Dexamethasone 8 mg orally twice daily for 5 days starting 1 day prior to docetaxel. 2. (optional) #2 and #3 as above)
Etoposide (VP-16) Type I. HSRs can occur and manifest as chills, fever, shortness of breath, low blood pressure or wheezing. The drug should be stopped and the reaction treated with dexamethasone, diphenhydramine, and epinephrine (if necessary). For mild reactions, the infusion may be restarted at a slower infusion rate along with IV fluids and gradually increased with blood pressure monitoring. 0.7 to 2% None
Bleomycin Type I. HSRs from Bleomycin can occur from the 1st dose on, especially in patients with lymphoma. These reactions manifest as chills, fever, shortness of breath, low blood pressure or wheezing. The drug should be stopped and the reaction treated with dexamethasone, diphenhydramine, and epinephrine (if necessary). 1 % Test dose of 0.5 to 1 unit should be given to all patients prior to the 1st dose of bleomycin

XIII.  Dermatologic Reactions from Chemotherapy
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Chemotherapy can cause several skin reactions. Vesicant drugs (nitrogen mustard, vincristine, etoposide, doxorubicin and other) can cause local skin reactions when injected but precautions and antidotes can minimize these reactions. Liposomal doxurubicin can also cause skin reactions. Specific drugs (bleomycin, paclitaxel) have the potential of causing allergic reactions. This can be minimized with adequate anti-allergic medications taken before chemotherapy. Patients receiving tretinoin can experience redness, dryness, itching and increase sensitivity to sunlight, thus should take adequate precautions. Finally, the Hand-foot syndrome is a painful redness, irritation and fissuration of the hands and soles seen with fluorouracil and capecitabine. Treatment of this syndrome is mainly support and moisturizing of the affected regions with creams and emolients.

XIV.  Fertility Effects of Chemotherapy
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Today, many young patients are cured of cancer after receiving chemotherapy. However, alterations in gonadal (reproductive) function are now recognized as a common complication of cancer chemotherapy. Women may experience premature gonadal failure, menopause, sterility and even osteoporosis (from estrogen deprivation). Men may have low sperm count and infertility. Other issues concerning cancer survivors are risks of complications of pregnancy, birth defects, and malignancy in their offspring.

Although many questions remain to be answered, your doctors will provide counseling and use newer strategies to prevent gonadal complications from chemotherapy. One approach is to use alternative hormonal therapies or preservation of sperm or eggs for future use.

Chemotherapy (especially cyclophosphamide) given to boys before or during puberty has resulted in 1% and 67% gonadal dysfunction, respectively. MOPP chemotherapy used in Hodgkin's inhibits virtually 90% of sperm function in men. Gonadal damage after puberty is usually assessed by analyzing the seminal fluid. The effects of various chemotherapy regimens on male spermatogenesis are shown in the table below. It appears that the major drugs that cause gonadal dysfunction are the alkylating agents such as cyclophosphamide, thiotepa, nitrogen mustard, and chlorambucil. For patients in whom fertility is spared, the outcome of pregnancies has not shown a higher incidence of congenital anomalies, spontaneous abortion, or neonatal mortality. There are fewer studies of fathers surviving cancer. In men with germ cell tumors, there has not been an excess of congenital anomalies and chromosomal abnormalities in their offspring. In addition, there was no difference in growth maturation. In pregnancy, fetal exposure to multidrug chemotherapy has been associated with minimal risk when chemotherapy was after the first trimester.

Disease Regimen % Low Sperm Count
Hodgkin's MOPP 85%
Hodgkin's ABVD 0
Testes Cancer Cisplatin, vinblastine, bleomycin 14-28%
Sarcoma Doxorubicin + Cyclophosphamide 65%

Disease Regimen % Amenorrhea
Ovarian Cancer Cisplatin, Vincristine, methotrexate, etoposide, actinomycin D 6%
Breast Cancer CMF 85%
Breast Cancer Cyclophosphamide 83%
Breast Cancer FU 9%
Hodgkin's MOPP 24%
Hodgkin's COPP 57%
Hodgkin's ABVD 0

Modified from M Perry. Chemotherapy Source Book. Williams and Wilkins. 2nd Edit 1997, pg. 813-832

XV.  Cardiac (heart) toxicity from Chemotherapy
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Some chemotherapy drugs, such as doxorubicin and daunorubicin or radiation therapy to the chest can cause adverse reactions on the heart. The effects (cardiac congestion, decreased exercise tolerance) are generally seen with prolong treatment, but can also occur faster. Your doctor may record an echo of your heart before and throughout the treatment. In case of damage to the heart, the drug may be stopped or modified. One other medication (Dexrazoxane) can be given to minimize the effects of chemotherapy on the heart muscle. Another way to decrease the adverse effect of chemotherapy is to give doxorubicin in a liposomal format.

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