Chemotherapy

Anti-cancer chemotherapy

The Cancer is the uncontrolled multiplication of cells, due to genetic mutations (damaged DNA) and, in an occasional way, to a hereditary predisposition to develop some Tumeur S.

The majority of the chimiotherapeutic substances function by stop of the Mitose (cellular division), by targeting the cells effectively dividing too quickly. As these substances can damage the cells, they are known as “Cytotoxique S”. Some of these molecules cause a true “cellular suicide”: the Apoptose.

Unfortunately, the researchers are not, to date, able to locate particular characteristics of the malignant cells , which would make them precisely identifiable (put besides some recent examples such the “Chromosome of Philadelphia” targeted by the Mésilate of Imatinib). That implies that other cells with fast division, the such cells responsible for the growth of the hair or regeneration of the intestinal epithelium, or the cells Sang uines, are also affected. This explains the side effects usually met, like the loss of the hair, the Infection S (destruction of the white globules), Anémie S (destruction of the red globules) and the Hémorragie S (destruction of the plate S). That requires sometimes means of fight against these side effects: setting in sterile room, blood transfusions, injections of érythropoïétine (EPO)…

However, certain molecules produce less side effects than others, authorizing the doctors to adjust the modes with the advantage of certain patients, in certain cases.

Since chemotherapy affects the cellular division, the tumors with strong growth (case of the Leucémie S or the Maladie of Hodgkin) are more sensitive to the treatment because most of the tumoral cells carry out cellular divisions uninterrupted.

The chemical substances used more effectively affect “the young” tumors (i.e. less differentiated) because generally, with more an high level of differentiation, the propensity of the cells to multiply decreases. Around the center of certain solid tumors, there is no more cellular division, which makes these cells insensitive with chemotherapy. Another problem with the solid tumors is that the agents used seldom reach the center of the tumor. To solve this problem, one has resorts to the Curiethérapie and, of course, to the surgery.

Types and posology of the drugs

The majority of the drugs in chemotherapy can be subdivided in: agents alkylants, Anti-metabolite S, Alkaloid S plants, inhibiters of the Topoisomérase, and Antibiotic S antitumor. All these drugs assign to a certain point the Mitose or the synthesis and the function of DNA.

Certain new agents do not act directly on the DNA. It is the case of the new inhibiter of the Tyrosine Kinase mésylate of imatinib , which directly targets a molecular anormality at certain types of cancer (Leucémie, Cancer of the colon).

Other drugs modify the behavior of the tumoral cells without to attack the cells directly. One uses in particular Hormone S for this kind of auxiliary therapy.

The proportioning of chemotherapy can be very difficult: a too weak amount will be ineffective against the tumor, whereas with excessive amount toxicity is intolerable for the patient. This is why in much of hospital were set up “processes of proportioning” in order to obtain correct treatments.

In general, proportioning is adjusted on the “surface of the body” of the patient, approximated by a calculation starting from its size and of its weight.

Agents alkylants

The agents alkylants are thus named thanks to their capacity to add a group Alkyle to a great number of electronegative groups under certain conditions (present in the cancer cells). They stop the growth of the tumor by binding together the Nucléotide S Guanine S in the double helix of DNA, attacking thus directly the DNA. The two bits cannot thus be held nor to separate, involving for the cell an incapacity to retort its DNA: the cell cannot then divide any more. These agents generally do not act specifically, some require a conversion in vivo into active substances (for example the cyclophosphamide).

Examples: cisplatine; carboplatine (or paraplatine); ifosfamide; chlorambucil; busulfan; thiotépa.

Anti-metabolites

The anti-metabolites take the place of the Purine S or the Pyrimidine S which are the elementary components of the DNA, nucleotides. These elements cannot then incorporate in the DNA at the time of the phase S of the cellular Cycle, thus stopping the development and the cellular division.

The anti-metabolites are divided into three groups according to the type of target which they reach:

antipyrimidines. For example the 5-fluoro-uracil (5FU) which inhibits the thymidylate synthase.
antipurines. The Fludarabine inhibits DNA polymerase, the DNA primase and the DNA Ligase I and is exclusively active at the time of the phase S (since these enzymes are very active at the time of the cellular replication).
antifolates. The Méthotrexate (antagonistic of the folate) inhibits the dihydrofolate réductase, enzyme essential with the synthesis of the Purine S and the Pyrimidine S.

The Hydroxyurée can also be classified among the anti-metabolites.

Vegetable alkaloids

These Alcaloïde S is derivatives of plants and blocks the cellular division by preventing the synthesis of the Microtubule S and the mitotic formation of the Fuseau. This spindle is vital for the cellular division, which cannot then be carried out any more.

Examples:

the Vinca-alkaloid S like the Vincristine, the Vinblastine or the Vinorelbine which bind to specific sites of the Tubuline, inhibit the assembly of the tubulines in microtubules.
the new group of Taxane S (Paclitaxel '' [[Taxis brevifolia] ] with its synthetic derivative Docétaxel) inhibits division by stimulating the polymerization of the tubulines, improving the formation and the stability of the microtubules. Those cannot then be degraded, and the chromosomes cannot migrate any more towards the poles of the core.

the épothilone S, products of a myxobactery, have the same mechanism of action as the Taxane S, and seem to have a similar anticancer activity.

Inhibiters of the topoisomérase

The topoisomérases are essential enzymes which maintain the Topologie DNA. The inhibition of the topoisomérase of the type I or type II gènent at the same time the transcription and the Réplication of the DNA by disturbing superenroulement DNA.

Examples of inhibiters of type I: derived from the Campthotécine.

Examples of inhibiters of type II: Amsacrine; anthracyclines; derived from the épipodophyllotoxine.

Antitumor antibiotics

There are many different antitumor antibiotics, but in general they prevent the cellular division by several means:

connection with the DNA while intercalating themselves between two adjacent nucleotide bases and by preventing them from separating;
inhibition of the ARN preventing the synthesis of enzymes;
gene of the cellular replication.

They are produced by various stocks of the bacterium Streptomyces . Examples:

Anthracycline S: Doxorubicine and Daunorubicine (which inhibits also the Topoisomérase II);
Actinomycine D; Mitomycine C; Plicamycine; Bléomycine. This last acts in a single way by oxidizing the complex DNA-bléomycine-Fe (II) thus forming free radicals, which induce damage and chromosomal aberrations.

Hormonothérapie

Several types of tumors can be treated using Hormone S. Of the cancers formed in fabrics such as the Glandes mammaires and the Prostate can be inhibited or stimulated by suitable changes in the regulation of the hormones.

the Stéroïde S (often the dexaméthasone) can inhibit the growth of the tumor or the associated edema (swollen fabric) and thus cause the regression of the tumor of the lymphatic Ganglion.
the cancer of the prostate is rather sensitive to the finastéride, an agent which blocks the peripheral conversion of the Testostérone into 5-hydroxytestostérone; in other terms, the 5-hydroxytestostérone which is supposed to stimulate the prostate is not manufactured any more, resulting in an inhibition from the cell multiplication of the cancer of the prostate.
the cells of breast cancer often express in an important way the receivers with the estrogen S and/or the Progestérone. The inhibition of the production (with inhibiters of Aromatase S) or action (with tamoxifene) of these hormones can often be used in partnership with the therapy. The cells mammaires are not stimulated indeed any more by the sex hormones, those not being able to stimulate the cells because of absence of the receivers.
of the agonists of GnRH ( Gonadotropin-releasing hormone or Gonadolibérine) as the gosereline have an effect of negative Rétrocontrôle paradoxical follow-up of the inhibition of the release of FSH and of LH if they are given uninterrupted. These hormones then do not stimulate any more the growth of their target cells, including/understanding the cells of the tumor concerned.

Other tumors are also sensitive to the hormones, although their specific mechanism remains still fuzzy.

Procedures of treatment

There is a certain number of strategies of administration of the chimiotherapeutic substances used today. Chemotherapy can be given in the intention to cure or it can aim to prolong the life or to mitigate certain symptoms.

One can combine chemotherapy with other treatments like the surgery or the Radiothérapie. Many cancers is treated of this manner currently.
the combined chemotherapy is a similar practice which indicates a treatment of the patient with several different drugs and simultaneously. These substances differ in their mechanism and their side effects. The most important advantage that brings is the minimization of the chances of resistance being able to develop against one of the agents used.
At the time of an néo-auxiliary chemotherapy (or preoperative treatment), chemotherapy aims at reducing the tumor, thus making a therapy local (like the surgery or the radiotherapy) less destructive and more effective.
On the other hand, a chemotherapy auxiliary (or post-operative) is used when the presence of the tumor is not very visible, but there are then risks of recurrence: that can indeed reduce the chances of resistance developed in the case of the development of the tumor. It is in addition useful to kill the cancer cells which would have migrated towards other parts of the organization. This therapy in the case of appears very effective new tumors which grow and whose cells divide quickly, and who are thus very sensitive to the treatment.

Many chemotherapies require that the patient can support the treatment. The Performance diagnoses is often used as measures to determine if a patient can receive a chemotherapy or if one must reduce the administered dose.

Modes of administration

Most of the time chemotherapy is managed by Intraveineuse. According to the patient, cancer, the stage of advance, the type of chemotherapy and proportioning, the treatment by intravenous will be applied either to patients remaining out of the Hôpital and coming there only for the treatment, or with patients having to be allowed during several days even several months in the hospital. Some agents are managed orally as it is the case for the prednisone, the melphalane and the gemcitabine. For an administration by intravenous continues, frequent or prolonged, several systems can be surgically installed in the vascular system in order to maintain an access there. The systems frequently used are:

the Catheter of Hickman (or Catheter tunnellized)
the Port-have-cath (or room with catheter)
the Line of PICC (for peripherally inserted central catheter or central catheter inserted périphériquement)

Those have a very small risk of infection, and have less risks to cause a major venous Thrombose (phlebitis) or a extravasation (escape of the product apart from the vessel where it must be introduced); the products used are often cytotoxic agents or caustics which are diluted in blood. In the case of a extravasation, these products can even damage to kill surrounding fabrics, from where interest of these techniques. They indeed abolish the need for repeated insertions of peripheral nozzles.

Side effects

The treatment can be exhausting for the patient. The current current chimiotherapeutic techniques have a certain number of side effects in general touching the body cells with fast division. Important side effects the most met (according to the agent):

Mucites, i.e. an ignition of the mucous membranes, in particular oral. It appears approximately 1 to 2 weeks after the beginning of the treatment and can empécher of drinking or eating when it is severe. Its prevention rests on the preliminary oral care, oral hygiene and on the action to suck ice floes (shown activity).
Fall of the hair
Nausea S and Vomiting S
Diarrhea or Constipation
Anemia
Depression of the Immune system from where Infection S (potentially mortals) and septic states
Hemorrhage
secondary Neoplasms
Cardiotoxicité
Hépatotoxicité
Néphrotoxicité

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