CARBOPLATIN - MEDICATIONS

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Carboplatin

Carboplatin is a platinum-based anticancer agent, belonging to the family of alkylating agents.

Carboplatin - Chemical Structure

It was introduced into therapy in the late 1980s and has since gained more and more importance in clinical treatment, mainly due to the significantly reduced side effects compared to its precursor cisplatin.
Carboplatin is on the World Health Organization's list of essential drugs, which includes a list of the most important drugs that must be present in a primary health care system.

Therapeutic indications

Carboplatin can be used alone or in combination with other antineoplastic drugs to treat various types of cancer, including:

Carcinoma of the ovary, advanced or not;
Small cell lung cancer
Head and neck cancer
Breast cancer
Bladder cancer
Carcinoma of the esophagus;
Cancer of the cervix;
Stomach cancer
Pleural mesothelioma.

Warnings

Treatment with carboplatin must be carried out under close supervision by a physician specialized in the administration of anticancer chemotherapy drugs.

Continuous monitoring of blood and urine composition is required before, during and after carboplatin therapy to assess kidney and liver activity.

During treatment with carboplatin, sun exposure is not recommended and in any case - in case of exposure - it is necessary to use sun creams with a high protection index. The drug - entering the circulation - is distributed in all tissues (including skin) and "Prolonged exposure to sunlight can cause redness and burns, even severe ones.

Interactions

The intake of drugs that cause - as a side effect - a reduction in the number of blood cells should be avoided in conjunction with the intake of carboplatin. This undesirable effect, in fact, could be worsened by carboplatin since it too has toxicity to the blood cells.
An example of a compound whose toxicity increases when administered concomitantly with carboplatin is the antipsychotic drug clozapine.

In addition, the administration of drugs that can damage the inner ear or kidneys, such as:

Capreomycin, an antibacterial used to treat tuberculosis;
Aminoglycoside antibiotics, For example gentamicin And streptomycin;
Polymyxin antibiotics, as the colistin;
Diuretics, as the furosemide.

The association of carboplatin with these drugs increases their toxicity, so concomitant administration should be avoided.

The concomitant intake of carboplatin e phenytoin, a drug used to treat epilepsy. Carboplatin, in fact, reduces the levels of phenytoin in the blood and this can lead to the recurrence of seizures.

Also the association with digoxin is to be avoided. Carboplatin decreases the blood concentration of digoxin, consequently decreases its therapeutic efficacy.

In any case, you should tell your oncologist if you are taking - or have recently been taking - any type of medication, including over-the-counter medicines, vitamins, supplements, homeopathic and / or herbal remedies.

Side effects

The side effects that carboplatin can cause are many. They depend a lot on the condition of the patient and the type of tumor he is suffering from.
It is not certain that the side effects occur all and with the same intensity in each patient, since there is a great variability from individual to individual.
Listed below are the main side effects that carboplatin can cause.

Severe allergic reactions

As with any drug, hypersensitivity to carboplatin can lead to the onset of severe allergic reactions. These reactions may manifest with swelling affecting the lips, face and / or neck with consequent difficulty in breathing; or skin reactions and / or skin reactions may appear. or hives.

Myelosuppression (bone marrow suppression)

Carboplatin can induce myelosuppression, the consequence of which is one reduced hematopoiesis (i.e. a reduced synthesis of blood cells).

Decreased blood cell production can lead to:

Anemia (reduced amount of hemoglobin in the blood);
Leukopenia (reduced number of white blood cells) resulting in increased susceptibility to contracting infections;
Thrombocytopenia (reduced number of platelets) leading to the appearance of bruises And abnormal bleeding with a increased risk of bleeding.

Nausea and vomit

As with many anticancer drugs, carboplatin can induce nausea and vomiting.
Vomiting can last anywhere from a few hours to a few days. To prevent this side effect, antiemetic (i.e. antivomiting) drugs may be administered, such as, for example, ondansetron.

Numbness and tingling in the hands and feet

This symptom is called peripheral neuropathy and is caused by the toxic action of carboplatin on nerve tissue. Usually, tingling is mild, but may worsen as chemotherapy continues.

Generally, this side effect disappears a few months after the treatment is finished. However, in some people the disorder does not regress and becomes chronic.

Diarrhea

It can occur in both mild and severe forms.
In case it occurs in a mild form, this symptom can be kept under control by using common antidiarrheal drugs.
If, on the other hand, the symptom presents itself in a severe form, it may be necessary to reduce the dose of carboplatin administered or even stop the treatment.
In any case, it is advisable to drink a lot in order to replenish lost fluids.

Loss of hair, hair and eyelashes

This symptom usually appears a few weeks after starting carboplatin chemotherapy, but - in some cases - it can occur even earlier. Hair, eyelashes, and body hairs can thin out or fall out completely. However, this side effect is reversible Hair and fluff begin to grow back a few months after the end of the treatment.

Pathologies of the oral cavity

Various oral side effects may occur during carboplatin therapy, including pain, dryness and the formation of small ulcers. To prevent this undesirable effect, a lot of fluids must be taken and regular cleaning of the teeth should be performed using a soft toothbrush, at least two or three times a day.
There may also be an alteration or loss of taste, but this is a temporary side effect that disappears shortly after the end of the chemotherapy.

Decreased liver function

Treatment with carboplatin may induce a temporary decrease in liver function, which however should return to normal after the end of therapy. In any case, patients are constantly monitored to keep liver activity under control before, during and after drug administration.

Amenorrhea

Carboplatin therapy can cause the menstrual cycle to be interrupted (amenorrhea). As a result, typical pre-menopausal symptoms such as hot flashes, excessive sweating and vaginal dryness may occur. These symptoms usually disappear after treatment is finished.

Cardiovascular pathologies

These side effects occur very rarely and consist of a increased blood pressure, stroke, heart failure and / or clots of blood.

Other side effects

Other side effects that carboplatin can induce are:

Fever and chills
Pallor;
Restlessness;
Damp skin
Hypotension;
Temporary vision disturbances, including temporary loss of vision;
Loss of appetite (anorexia).

These side effects are not very common, but it is essential to inform the oncologist if they appear.

In addition, in some cases, a secondary tumor may arise but this type of adverse effect occurs very rarely.

Since carboplatin is administered intravenously, damage to the administration site may occur, such as redness, swelling, pain or fluid leaking from the cannula during administration.

Mechanism of action

Carboplatin is an alkylating agent and is capable of forming bonds with the two strands that make up DNA.
DNA is made up of four basic units called nitrogenous bases, these molecules are cytosine, thymine, adenine and guanine.
Carboplatin carries out its cytotoxic action in a similar way to that of its precursor cisplatin; it therefore acts by binding to a nitrogen atom present in the guanine structure. However, it appears that carboplatin is also capable of forming covalent bonds (i.e. strong bonds that are not easily broken) with adenine and cytosine.
The binding of carboplatin to DNA prevents it from being transcribed and replicated. Consequently, if the cells are no longer able to divide, then they undergo the mechanism of programmed cell death defined apoptosis.

Method of Use - Dosage

Carboplatin is administered for intravenous infusion (drip infusion); it is presented as a clear solution which may be colorless or pale yellow in color.
It can be administered through three different routes:

Through a cannula (a thin tube) that is inserted into a vein in an arm or hand;
Through a central venous catheter which is inserted subcutaneously into a vein near the collarbone;
Across the line PICC (Peripherally Inserted Central Catheter), in this case the catheter is inserted into a peripheral vein, usually of an arm. This technique is used for the administration of anticancer drugs for a prolonged period of time, therefore for long chemotherapeutic regimens.

The usual adult dose of carboplatin is 400 mg / m2, administered as a single intravenous dose over 15 to 60 minutes.

The use of carboplatin in children is not recommended.

In elderly patients over 65 years of age the dosage should be adjusted according to the patient's condition.

In case the patient suffers from kidney dysfunction, it is necessary to decrease the amount of drug administered.

In case of carboplatin overdose there is no antidote: the oncologist will have to stop the therapy and adequately treat the symptoms deriving from taking too high a dose of the drug.

Pregnancy and breastfeeding

Carboplatin should not be used during pregnancy - unless specifically prescribed by the oncologist - due to possible abnormalities that may arise in the developing fetus.

Women should not breastfeed during treatment with carboplatin.

If pregnancy is suspected during carboplatin therapy, the oncologist should be informed immediately. If pregnancy is confirmed, genetic counseling should be provided.

Patients - both male and female - and their partners should take precautions to prevent pregnancy, both during and after treatment with carboplatin, for a period of at least six months after the end of chemotherapy.

Young male patients may experience infertility following carboplatin therapy. Infertility is not always a reversible side effect, sometimes it becomes permanent.