Chemotherapy

Chemotherapy is a therapeutic technique that consists of the administration of chemical substances for the shrinkage of different conditions, commonly associated with cancer therapy.

Currently, it is one of the most widely used therapeutic methods, using a wide variety of antineoplastic drugs for this. In general, they work by preventing cancer cells from growing, dividing, and producing more cells. Because cancer cells generally grow and divide faster than normal cells, chemotherapy has more of an effect on cancer cells. However, the drugs used for chemotherapy are powerful and can cause damage to healthy cells. This damage causes the side effects associated with chemotherapy.

Chemotherapy is given so that the health care team can give chemotherapy in the clinic, doctor's office, or hospital. Some types of chemotherapy are given by mouth, and can be taken at home.

Historical overview

The term chemotherapy generally refers to the treatment of cancer, although its historical meaning is broader. In a simpler sense, chemotherapy refers to the use of antineoplastic drugs or chemotherapeutic drugs to fight cancer. As such, the term has also been used for non-oncological use, such as the use of antibiotics (antibacterial chemotherapy ). In that sense, the first modern chemotherapeutic agent was arsphenamine, an arsenic compound discovered in 1909 and used to treat syphilis. Later, sulfonamides and penicillin followed. Other uses that have been termed chemotherapy are the treatment of autoimmune diseases, such as multiple sclerosis, dermatomyositis, polymyositis, lupus, rheumatoid arthritis, and suppression of transplant rejection (see immunosuppression).

Specific chemotherapy for cancer began in the 1940s, with the first uses of mustard gas and drugs antagonistic to folic acid as antineoplastic agents.

Cancer therapy

Drugs used in cancer chemotherapy usually work by stopping cancer cells from growing, dividing, and making more cells. The main drugs are known as cytostatics or cytotoxics. Chemotherapy is used in different ways at different times. This includes the following:

• For cancer that moves through the vascular or lymph system and forms new tumors, it is the purpose of metastatic cancer.
• After surgery or radiation therapy, cancerous microscopic cells that may have travelled to other parts of the body are eliminated, adjuvant chemotherapy is named.
• As the only treatment. For example, to treat cancers of the blood or lymph system, such as leukemia and lymphoma.
• The cancer that after treatment re-appears is called recurrent cancer; for example, recurrent breast cancer.
• Before surgery or radiation therapy, neoadjuvant chemotherapy is needed to reduce tumors.

Uses of Chemotherapy

Chemotherapy is usually not the only treatment for cancer, as it is often combined with surgery and radiation therapy, a modality called combined or multidisciplinary treatment.

Depending on the purpose and drug combination, the following types of chemotherapy are distinguished:

• Curative: its goal is to cure the disease, when it is in a suitable phase for it.

• Palliative: its intention is to control the symptoms produced by the tumor, which is already in an advanced and inoperable phase. This is why it seeks to improve to the extent possible the quality of life of the patient as well as increase their survival.

• Adjuvant: is usually given after a major treatment such as surgery, to decrease the incidence of metastasis.

• Neoadyuvante or induction: it starts before any surgical treatment or radiation therapy, in order to evaluate the effectiveness of the treatment. It decreases the tumor stage, which can improve the results of surgery and radiation therapy, and sometimes the response obtained when arriving at surgery is a prognostic factor.

• Monochemyotherapy: administration of a single antitumoral drug. It consists of a judicious rotation of available drugs (sequential monochemy therapy), in cycles in which a single compound is administered until the control of the pathology or to demonstrate clinical evidence of its inefficiency. With monochemotherapy, the best-responsive neoplasms (leukemias and lymphomas) hardly exceed 30 percent of remission, while in solid tumors, even treated with more effective drugs and in the most favorable conditions, there is no adequate response beyond 10-15 percent. For this reason, the application of sequential monochemotherapy today finds restricted application in the treatment of neoplasms.

• Polychemyotherapy: combination of several cytotoxics that act with different mechanisms of action, synergy, in order to decrease the dosage of each individual drug and increase the therapeutic power of all substances together. It is usually defined according to the type of drugs that form the association, dose and time in which it is administered, forming a chemotherapy scheme.

• Concomitant radiation therapy: is administered concurrently or at the same time with radiation therapy, in order to enhance the effect of radiation or to act spatially with it, i.e. to enhance the local effect of radiation and to act systemically with chemotherapy.

Both in monochemotherapy and in polychemotherapy, and in accordance with both the management guidelines and the clinical conditions of the patient, medications can be administered concomitantly with antineoplastics to manage secondary symptoms, such as ondansetron (antiemetic), amifostine (nephroprotection), dexrazoxane (cardioprotection), mesna (used to reduce bladder irritation), or dexamethasone.

Mechanism of action

The essential objective of chemotherapy is to destroy tumor cells, in order to achieve the disappearance, arrest or reduction of the disease. The drugs used in this type of treatment are called antineoplastic or chemotherapeutic.

The process of division in healthy cells is tightly regulated by control mechanisms, which tell the cell when to divide. Malignant tumors are characterized precisely by the opposite, since they are formed by altered cells capable of multiplying uncontrollably and even invading and affecting neighboring or distant organs, which is called metastasis. Thus, chemotherapy acts in the division phase of the tumor cell, preventing its multiplication and eventually destroying it. With time, if the chemotherapy works, it will achieve a decrease or disappearance of the malignant tumor.

Anticancer drugs reach virtually all body tissues, without differentiating malignant cells from healthy ones. This causes the patient a series of side effects, which generally disappear once the treatment is finished. The healthy cells most frequently damaged involve the cells of the bone marrow, digestive tract, and hair follicle, leading to the most common side effects of chemotherapy, which are: immunosuppression, asthenia, mucositis, and alopecia. among others. Such effects are usually transient, although if they are not controlled or tolerated by the patient they can produce toxicity and lead to temporarily suspending chemotherapy treatment.

Therefore, in an attempt to mitigate the side effects, anticancer drugs have been developed in recent years that work directly against abnormal proteins in cancer cells, called targeted therapy, commonly known as immunotherapy.

Types of antitumor drugs

There are more than one hundred antineoplastic drugs, which are usually classified into the following groups:

• Alkylating agents: their general action mechanism is the damage induced to cellular DNA (both neoplastic and healthy) by incorporating alkylo groups, and in this way alter or avoid cell duplication. Examples: clorambucil, melfalán.
• Antimetabolites: substances similar to natural components:
  • Folic acid analogue: metotrexate.
  • Analogue of purine: 6-mercaptopurine.
  • Pyrimidine analogues: 5-fluorouracil, ara-c.
• Vinca alkaloids: etoposide, tenlipid, vincristine, vinblastine.
• Derived from platinum.

Intravenous administration of doxorubicin. This medication is often used in combination chemotherapy to combat different types of cancer, usually as a component of various treatment regimens. Doxorubicin has a characteristic red colour.

Some of the cytostatic active principles are the following:

• Aldesleukina. It is used for the treatment of metastatic renal cell carcinoma.
• Bexaroteno. It is used in the treatment of skin lymphomas such as fungoid mycosis.
• Bleomycin. It is used for the treatment of Hodgkin lymphoma.
• Capecitabine. It is used for the treatment of colon cancer, breast cancer.
• Carboplatin. It is used in ovarian, lung, epidermoid head and neck and neoadjuvant treatment of bladder carcinoma.
• Cisplatin. It is used for metastatic testicular carcinoma, ovary and advanced bladder, as well as the refractory carcinoma of squamous cells of head and neck.
• Docetaxel. Antimicrotubulous agent indicated in the treatment of advanced breast cancer (1.a and 2nd line), adjuvant breast cancer, non-microcytic lung cancer (1.a and 2nd line), metastatic prostate cancer, gastric cancer, and head and neck cancer. His commercial name is Taxotere.
• Doxorubicin. Antibiotic antitumoral, its commercial name is Adriblastina.
• Epirubicin. It's a cytostatic antibiotic from the anthracycline group.
• Fludarabine. Phosphate fludarabine is used in the treatment of patients with chronic B-cell lymphocytic leukemia (LLC).
• Gemzar. Commercial name of gemcitabine, which is usually used in the treatment of pancreatic cancer.
• Irinotecan. It is prescribed for the treatment of advanced colorectal cancer and is also integrated into polychemotherapy schemes such as FOLFIRINOX.
• Metotrexate. It is also used for antineoplastic chemotherapy, rheumatoid arthritis, psoriasis, poliomyelitis, sarcoidosis and reactive arthritis.
• Mitoxantrona. It is used in the treatment of metastatic breast carcinoma and non-hodgkinian lymphoma.
• Oxaliplatin. It is authorized for the first-line treatment of metastatic colorectal cancer in association with 5-fluorouracillus and leucovorin, and for adjuvant treatment of stage III colon cancer. It is also integrated into the FOLFIRINOX scheme for pancreatic cancer.
• Paclitaxel. It is a medicine used for the treatment of certain ovarian, breast and lung diseases. Its use in combination with albumin and gemcitabine nanoparticles has also now been widespread, which is marketed by the name of Abraxane.
• Rituximab. It is used in the treatment of Hodgkin lymphoma.
• Vinblastine and vincristine. They are oncolytic drugs that cause the interruption of cell division at the stage of metaphase.
• Vinorelbine. It is used in the control of certain diseases located in the chest (pulmonary and breasts).

Administration

Chemotherapy is given in cycles, alternating periods of treatment with periods of rest. This is essential to give the healthy cells of the body the necessary time to recover, in such a way that they are able to tolerate a new cycle of treatment, with less toxicity.

Depending on the type of cancer, its stage, the patient's condition, and the drugs, chemotherapy can be given intravenously or orally.

Intravenous route

It is the most widely used route of administration. Sometimes, to avoid repeatedly puncturing a fine vein or in prolonged treatments, a catheter is used, thus avoiding phlebitis.

For the infusion of drugs, infusion pumps are used, which control the passage of chemotherapy into the body.

Oral route

This route is only possible for drugs that can be absorbed through the stomach or intestine.

Place of administration

The preparation of chemotherapy, with prior authorization from the oncologist, is generally carried out in the hospital's pharmacy service, since important security measures are required.

Nurses who are experts in the administration of chemotherapy are in charge of placing the line and the infusion system. The most widely used route is that of the subcutaneous or superficial veins of the upper limb.

Treatment is usually given in a day hospital.

In certain circumstances, depending on the type of drugs or as a consequence of toxicity, hospitalization for several days is necessary.

Limitations

First of all, chemotherapy, being non-specific, affects healthy tissues, giving rise to side effects that, although transient, can become chronic. This can be extremely debilitating for the patient, especially if the chemotherapy is given for long, continuous periods of time. On the other hand, as the tumor progresses, cells can develop resistance to chemotherapy, favoring the development of the disease. For this reason, it is common for the same drug to be used in the treatment of different tumors, varying the doses or combining it with other different drugs.

Side effects

Chemotherapy can harm cancer patients because it also destroys normal cells, especially those that divide more rapidly. These effects, although they are usually transient, can become chronic, which can extremely debilitate the patient, especially if it is administered for long and continuous periods of time. In some cases, when the side effects are very intense, toxicity occurs, which can lead to temporary cessation of antineoplastic treatment. Side effects depend on the chemotherapy agent and the most important are:

• Alopecia: is the most visible side effect, due to the change of body image, and that most psychologically affects the sick. However, hair loss depends on the amount and type of drug, not happening in all cases. In addition, between four and six weeks after the treatment is completed, the hair grows again.
• Nausea and vomiting, which can be relieved with antiemetics such as metoclopramide or with serotonin type 3 receptor antagonists, such as metoclopramide dolasetron, Granisetron and ondansetron.
• Diarrhea or constipation.
• Anemia, due to the destruction of the bone marrow, which decreases the number of red blood cells. Sometimes, blood transfusion or erythropoietin administration must be used to mitigate anemia.
• Immunodepression: virtually all chemotherapy regimens can cause a decrease in the effectiveness of the immune system, such as neutropenia that can lead to infection, sepsis and death if not detected and treated on time. Neutropenia can be solved with the management of granulocyte colony growth factor (G-CSF) granulocyte-colony stimulating factor) like the filgrastim.
• Hemorragia, due to the decrease in platelets due to the destruction of the bone marrow.
• Cardiotoxicity: chemotherapy increases the risk of cardiovascular disease (e.g.: adriamicin).
• Hepatotoxicity: mainly affects the liver and its functions.
• Nephrotoxicity: mainly affects the kidneys and their functions.
• Tumoral Lysis Syndrome: It occurs with the destruction by chemotherapy of large tumor malignant cells such as lymphomas. This serious and fatal side effect is prevented at the beginning of treatment with various therapeutic measures.
• Decrease in coagulation factors: when the body is in a state of emergency and weakened, several processes are atrophy, including coagulation factors and if we add to the decrease in platelets, the patient will have difficulty forming thrombos.
• Ototoxicity. Temporary or permanent damage to the cells of the inner ear, causing tinnitus, vertigo, problems of balance and hearing impairment.
• Sterility: Some chemotherapeutic drugs destroy sex hormone and gamete producing cells, incapacitating the person to procreate.
• Astenia
• Cognitive disorder

Local chemotherapy

It is the form of local (regional) administration of antineoplastic chemotherapy. Its objective is to achieve high concentrations of an antineoplastic drug in the tumor region with the least possible systemic toxicity. For example, intracavitary chemotherapy, whether intravesical, intraperitoneal, intrapleural, intradural, and intra-arterial chemotherapy. Within this last group, there is isolated regional perfusion, intra-arterial infusion, and different intermediate techniques with a greater or lesser isolation of the regional blood circulation to be treated. Other examples of intracavitary chemotherapy: intravesical instillation of mitomycin-c as adjuvant treatment of bladder cancer, and intraperitoneal chemotherapy as adjuvant treatment of ovarian cancer.