Chemotherapy [2]

Chemotherapy [2]

Chemotherapeutic agents

Chemotherapeutic agents are drugs that basically affect a variety of cell cycle phases by completely or partially interrupting cell division or by destroying them. This is why they’re called cytotoxic (harmful or toxic to cells) drugs and the therapy itself, cytotoxic therapy or chemotherapy. At present several dozen chemotherapy treatments are available and every day thousands of people receive one of these therapies. Cytotoxic drugs can be used on their own (monotherapy) or in combination with other drugs that act differently on cell cycles. Chemotherapy drugs work most successfully on cells which divide quickly. Unfortunately, this also includes not only cancer cells, but also many healthy cells – germ cells, haematopoietic cells, mucous membrane and hair follicle cells. Therefore, by destroying or inhibiting tumour cells, other cells also suffer. However, there are also tumours that grow very slowly, and the proportion of cells engaged in active division is quite small. In such cases, chemotherapy alone can prove to be unsuccessful and can cause more side effects than therapeutic benefits.

Unfortunately, none of the cytotoxic drugs at our disposal today are selective enough to target only cancer cells. The breadth of their therapeutic activity is very narrow. By increasing the dosage, serious side effects will develop. However, by decreasing the dosage we might have less side effects, yet it’s entirely possible that the treatment will have less of an effect on the cancer cells. In many cases, doctors know what kinds of complications to expect when using specific drugs. However, it’s also possible to come across rare and unexpected side effects. This simply can’t be foreseen.

All chemotherapy drugs can be divided into several groups. Alkylating agents are the first chemical substances, which were originally obtained from mustard gas. They directly damage a cell’s DNA in any phase of its cycle. Alkylating agents are also effective in lower doses and they can be used in the treatment of a variety of different tumours. The toxic effects on haematopoietic cells depends on the dosage. Alkylating agents can not only act cytotoxically, but they can also be teratogenic (harmful to an embryo or foetus) and carcinogenic (cancer causing). It has been observed that leukaemia can develop in patients 5 – 10 years after using these drugs in high doses. This group of drugs also includes nitrogen mustards (cyclophosphamides and ifosfamides), nitrosoureas (carmustine, lomustine, et al.), aziridines (thiotepa, mitomycin C, et al.), platinum compounds (oxaliplatin) and a whole range of other drugs (procarbazine, dacarbazine, temozolomide, et al.)

Antimetabolites, which are reminiscent of natural pyrimidines or purines, incorporate themselves into the cell’s DNA and RNA during the S phase of cell growth, thus interfering with cell division. Antimetabolites supress specific pathogenic stages of cell metabolism – the normal synthesis of DNA by blocking cell replication (division) and causing the death of the cell. The drugs of this group were already known to science since the beginning of the 1950s and include folic acid antagonists (methotrexate and pemetrexed), purine antagonists (mercaptopurine), pyrimidine antagonists (5-fluorouracil and capecitabine) and many other antagonists (tegafur, gemcitabine, fludarabine, et al.).

Microtubule-binding agents. Microtubules are essential elements of the mitotic spindle, which ensure the process of mitosis and other actions in the cell. By damaging the mitotic spindle, mitosis or cell division is blocked. For this reason, these drugs are also called mitotic inhibitors or mitotic poisons. Many widely used drugs belong to this group of chemotherapeutic drugs. The alkaloids of myrtle vines (vinca minor) form the basis for vincristine, vinblastine and vinorelbine. In addition to inhibiting the cell cycle, they also have the ability to inhibit angiogenesis. The neurotoxicity commonly associated with vincristine (toxic effects on nerve fibres) depends on the dosage and the duration of use. Patients may experience motor function disorders, autonomic neuropathy with constipation, urinary retention and hypertension as well as fainting spells and visual disturbances. No doctor can predict if you’ll have any of these side effects. Therefore, if you have any suspicious symptoms, don’t hesitate to tell your doctor. Neurotoxicity is less common with vinblastine, but bone marrow suppression and mucosal damage are more common. The main factor that limits the use of vinorelbine is its supressing effect on bone marrow and blood cell production. However, these days there are many options for minimizing or even eliminating side effects, so you should find out all you can about supportive therapy (a treatment that helps combat the side effects of chemotherapy). Other alkaloids derived from the European yew tree (Genus Taxus) or their synthetic analogues can also be considered microbubble-binding agents. The mechanism of action of the taxanes differs from those of the vinca minor alkaloids. By disrupting the reorganisation of the microtubules, taxanes cause a long-term delay in mitosis in both the metaphase and anaphase. In lower concentrations taxanes also cause apoptosis (the death of programmed cells) and counteract the formation of new blood vessels (an antiangiogenic effect). Taxanes also act as radiosensitizers (increasing cell-sensitivity to radiation) by blocking the cell’s cycle in the G2 and M phases when they are most sensitive to radiation. The most serious side effect of taxanes is neutropenia (the suppression of leukocytes, which are responsible for the body’s fight against infections). Paclitaxel is a semi-synthetic alkaloid, and since it isn’t soluble in water, it is bound to a carrier, which often causes an allergic reaction. Therefore, premedication or allergy reducing therapy is essential prior to administering paclitaxel. Docetaxel has a more powerful effect and is also less likely to cause neurotoxicity, but patients often suffer from hand-foot syndrome, when the skin in these areas is covered with itchy, red splotches.

Antitumor antibiotics and similar synthetic forms. Most of these drugs are derived from different Streptomyces species. Different drugs act slightly differently on DNA, blocking its replication. The main side effects include myelosuppression (bone marrow suppression), mucositis (inflamed or damaged mucous membranes), cumulative cardiomyopathy (heart muscle damage), nausea and vomiting, alopecia (hair loss), vein irritation, urine, nail and skin pigmentation, photosensitivity (hypersensitivity to sunlight) and radiosensitization (redness, itching and lesions in irradiated areas 3 – 7 days after treatment). Patients usually recognise the most commonly used drugs of this group by their red colour (red system or red devil chemo). These include several groups of medicines. One of the most commonly used are anthracyclines (doxorubicin, epirubicin and daunorubicin). Mitoxantrone, bleomycin and dactinomycin are the most commonly used drugs of the anthracenedione group.

Topoisomerase inhibitors. Topoisomerases are essential enzymes that ensure the formation of the DNA double helix and its proper functioning. Topoisomerase inhibitors are divided into two groups, I and II, and include such drugs as camptothecin (irinotecan and topotecan) and plant-based podophyllotoxins (etoposide and teniposide).

These are only general groups of drugs. New drugs and drug groups are created all the time making categorisation more complicated, especially when one needs to combine a variety of drugs with different mechanisms of action to simultaneously reduce side effects, while increasing the potential to destroy cancer cells. Today classic chemotherapy is often combined, potentiated or sequenced with other groups of drugs and therapeutic methods.

And if I don’t want to chemicalize myself?

Fear, preconceptions, doubts and certainty that chemotherapy is something bad is usually rooted in a lack of faith in today’s cancer treatment methods in general (my neighbour had chemo but died anyway) or a sad personal experience (someone you know suffered from nausea and vomiting, while another had terrible fatigue or lost their hair). Still others complain that they don’t see eye to eye with their doctor and therefore don’t trust them. You, of course, have the right to refuse chemotherapy. However, by doing this you run the risk of making your disease uncontrollable. In any case, you have the right to seek a second opinion from another doctor and then to decide what to do.

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