The majority of chemotherapeutic drugs can be divided in to alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents.
Other agents are mechlorethamine, cyclophosphamide, chlorambucil, ifosfamide.
- Depression of the immune system, which can result in potentially fatal infections. Although patients are encouraged to wash their hands, avoid sick people, and to take other infection-reducing steps, about 85% of infections are due to naturally occurring microorganisms in the patient's own gut and skin. This may manifest as systemic infections, such as sepsis, or as localized outbreaks, such as shingles. Sometimes, chemotherapy treatments are postponed because the immune system is suppressed to a critically low level.
- Fatigue. The treatment can be physically exhausting for the patient, who might already be very tired from cancer-related fatigue. It may produce mild to severe anemia. Treatments to mitigate anemia include hormones to boost blood production (erythropoietin), iron supplements, and blood transfusions.
- Tendency to bleed easily. Medications that kill rapidly dividing cells or blood cells are likely to reduce the number of platelets in the blood, which can result in bruises and bleeding. Extremely low platelet counts may be temporarily boosted through platelet transfusions. Sometimes, chemotherapy treatments are postponed to allow platelet counts to recover.
- Gastrointestinal distress. Nausea and vomiting are common side effects of chemotherapeutic medications that kill fast-dividing cells. This can also produce diarrhea or constipation. Malnutrition and dehydration can result when the patient doesn't eat or drink enough, or when the patient vomits frequently, because of gastrointestinal damage. This can result in rapid weight loss, or occasionally in weight gain, if the patient eats too much in an effort to allay nausea or heartburn. Weight gain can also be caused by some steroid medications. These side effects can frequently be reduced or eliminated with antiemetic drugs. Self-care measures, such as eating frequent small meals and drinking clear liquids or ginger tea, are often recommended. This is a temporary effect, and frequently resolves within a week of finishing treatment.
- Hair loss. Some medications that kill rapidly dividing cells cause dramatic hair loss; other medications may cause hair to thin. These are temporary effects: hair usually starts growing back a few weeks after the last treatment, sometimes with a tendency to curl that may be called a "chemo perm".
Damage to specific organs may occur, with resultant symptoms:
- Cardiotoxicity (heart damage)
- Hepatotoxicity (liver damage)
- Nephrotoxicity (kidney damage)
- Ototoxicity (damage to the inner ear), producing vertigo
Immunosuppression and myelosuppression
Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells, and platelets. The latter two, when they occur, are improved with blood transfusion. Neutropenia (a decrease of the neutrophil granulocyte count below 0.5 x 109/litre) can be improved with synthetic G-CSF (granulocyte-colony stimulating factor, e.g., filgrastim, lenograstim).
In very severe myelosuppression, which occurs in some regimens, almost all the bone marrow stem cells (cells that produce white and red blood cells) are destroyed, meaning ''allogenic'' or ''autologous'' bone marrow cell transplants are necessary. (In autologous BMTs, cells are removed from the patient before the treatment, multiplied and then re-injected afterwards; in ''allogenic'' BMTs the source is a donor.) However, some patients still develop diseases because of this interference with bone marrow.
In Japan the government has approved the use of some medicinal mushrooms like ''Trametes versicolor'', to counteract depression of the immune system in patients undergoing chemotherapy.
Nausea and vomiting
Chemotherapy-induced nausea and vomiting (CINV) is common, but use of less emetogenic chemotherapy and better antiemetics have reduced the risks in recent times. Stimulation of the vomiting center in the brain results in the coordination of responses from the diaphragm, salivary glands, cranial nerves, and gastrointestinal muscles to produce the interruption of respiration and forced expulsion of stomach contents known as retching and vomiting. The vomiting center is stimulated directly by afferent input from the vagal and splanchnic nerves, the pharynx, the cerebral cortex, cholinergic and histamine stimulation from the vestibular system, and efferent input from the chemoreceptor trigger zone (CTZ). The CTZ is in the area postrema, outside the blood-brain barrier, and is thus susceptible to stimulation by substances present in the blood or cerebral spinal fluid. The neurotransmitters dopamine and serotonin stimulate the vomiting center indirectly via stimulation of the CTZ.
The 5-HT3 inhibitors are the most effective antiemetics and constitute the single greatest advance in the management of nausea and vomiting in patients with cancer. These drugs are designed to block one or more of the signals that cause nausea and vomiting. The most sensitive signal during the first 24 hours after chemotherapy appears to be 5-HT3. Blocking the 5-HT3 signal is one approach to preventing acute emesis (vomiting), or emesis that is severe, but relatively short-lived. Approved 5-HT3 inhibitors include Dolasetron (Anzemet), Granisetron (Kytril, Sancuso), and Ondansetron (Zofran). The newest 5-HT3 inhibitor, palonosetron (Aloxi), also prevents delayed nausea and vomiting, which occurs during the 2–5 days after treatment. A granisetron transdermal patch (Sancuso) was approved by the FDA in September 2008. The patch is applied 24–48 hours before chemotherapy and can be worn for up to 7 days depending on the duration of the chemotherapy regimen.
Another drug to control nausea in cancer patients became available in 2005. The substance P inhibitor aprepitant (marketed as Emend) has been shown to be effective in controlling the nausea of cancer chemotherapy. The results of two large controlled trials were published in 2005, describing the efficacy of this medication in over 1,000 patients.
Some studies and patient groups claim that the use of cannabinoids derived from marijuana during chemotherapy greatly reduces the associated nausea and vomiting, and enables the patient to eat. Some synthetic derivatives of the active substance in marijuana (Tetrahydrocannabinol or THC) such as Marinol may be practical for this application. Natural marijuana, known as medical cannabis is also used and recommended by some oncologists, though its use is regulated and not legal everywhere.
Secondary neoplasm
The development of secondary neoplasia after successful chemotherapy and or radiotherapy treatment has shown to exist. The most common secondary neoplasm is secondary acute myeloid leukemia, which develops primarily after treatment with alkylating agents or topoisomerase inhibitors. Other studies have shown a 13.5 fold increase from the general population in the incidence of secondary neoplasm occurrence after 30 years from treatment.
Other side effects
In particularly large tumors, such as large lymphomas, some patients develop tumor lysis syndrome from the rapid breakdown of malignant cells. Although prophylaxis is available and is often initiated in patients with large tumors, this is a dangerous side effect that can lead to death if left untreated.
Less common side effects include pain, red skin (erythema), dry skin, damaged fingernails, a dry mouth (xerostomia), water retention, and sexual impotence. Some medications can trigger allergic or pseudoallergic reactions.
Some patients report fatigue or non-specific neurocognitive problems, such as an inability to concentrate; this is sometimes called post-chemotherapy cognitive impairment, referred to as "chemo brain" by patients' groups.
Specific chemotherapeutic agents are associated with organ-specific toxicities, including cardiovascular disease (e.g., doxorubicin), interstitial lung disease (e.g., bleomycin) and occasionally secondary neoplasm (e.g., MOPP therapy for Hodgkin's disease).
Further Reading
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