drugs

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, above all thanks to the greatly reduced side effects compared to its cisplatin precursor.

Carboplatin is on the list of essential drugs of the World Health Organization; This list includes a list of the most important drugs that must be present in a basic health system.

Therapeutic indications

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

  • Advanced and non-advanced ovarian cancer;
  • Small cell lung carcinoma;
  • Carcinoma of the head and neck;
  • Breast cancer;
  • Bladder cancer;
  • Esophageal carcinoma;
  • Cervical cancer of the uterus;
  • Carcinoma of the stomach;
  • Pleural mesothelioma.

Warnings

Treatment with carboplatin should be carried out under the strict supervision of a doctor who specializes in the administration of anticancer chemotherapy drugs.

Before, during and after therapy with carboplatin it is necessary to continuously monitor blood and urine composition to evaluate liver and kidney activity.

During treatment with carboplatin, exposure to the sun is not recommended and in any case - in case of exposure - it is necessary to use sunscreen 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 sunburn, even serious.

Interactions

Taking medications that cause - as a side effect - a reduction in the number of blood cells should be avoided in conjunction with carboplatin. This undesirable effect, in fact, could be worsened by carboplatin since it also has toxicity on the blood cells.

An example of a compound whose toxicity increases when co-administered with carboplatin is the antipsychotic drug clozapine .

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

  • Capreomycin, an antibacterial used for the treatment of tuberculosis;
  • Aminoglycoside antibiotics, such as gentamicin and streptomycin ;
  • Polymyxin antibiotics, such as colistin ;
  • Diuretics, such as furosemide .

The combination of carboplatin with these medicines increases their toxicity, so that concomitant administration should be avoided.

The concomitant intake of carboplatin and phenytoin, a drug used to treat epilepsy, should be avoided. In fact, carboplatin reduces the levels of phenytoin in the blood and this can lead to the reappearance of epileptic seizures.

The association with digoxin is also to be avoided. Carboplatin reduces the blood concentration of digoxin, consequently decreasing its therapeutic efficacy.

In any case, it is necessary to inform the medical oncologist if you are taking - or if you have recently been taken - drugs of any kind, including over-the-counter drugs, vitamins, supplements, homeopathic and / or herbal remedies.

Side effects

There are many side effects that carboplatin can cause. They depend a lot on the condition of the patient and the type of cancer he is suffering from.

It is said that the side effects do not all present themselves with the same intensity in each patient, since there is a great variability from individual to individual.

The main side effects that carboplatin can cause are listed below.

Serious allergic reactions

As with any drug, hypersensitivity to carboplatin can lead to severe allergic reactions. These reactions can occur with a swelling that affects the lips, face and / or neck resulting in difficulty breathing; or skin and / or hives may appear.

Myelosuppression (bone marrow suppression)

Carboplatin may induce myelosuppression, the consequence of which is reduced haematopoiesis (ie reduced synthesis of blood cells).

The decrease in blood cell production can lead to:

  • Anemia (reduced amount of hemoglobin in the blood);
  • Leukopenia (reduced number of white blood cells) with consequent increased susceptibility to infection contraction ;
  • Plateletopenia (reduced number of platelets) leading to bruising and abnormal bleeding with an increased risk of bleeding .

Nausea and vomit

As with many anticancer drugs, carboplatin can induce nausea and vomiting.

Vomiting can last from a few hours to a few days. To prevent this side effect antiemetic drugs (ie anti-emulsion) can 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 nervous tissue. Typically, the tingling occurs in mild form, but may worsen during continued chemotherapy.

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

Diarrhea

It can occur both in mild and severe form.

In the event that it occurs in mild form, this symptom can be kept under control by the use of common antidiarrheal drugs.

If, on the other hand, the symptom occurs in a severe form, it may be necessary to reduce the dose of carboplatin administered or even interrupt 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 after a few weeks from the start of chemotherapy with carboplatin, but - in some cases - it can also occur earlier. The hair, eyelashes and hairs that line the body may thin out or fall completely. However, this side effect is reversible. Hair and hair begin to grow back a few months after the end of treatment.

Oral cavity disorders

During carboplatin therapy various side effects may occur at the level of the oral cavity, including a sensation of pain, dryness and formation of small ulcers. To prevent this unwanted effect, you must take plenty of fluids and regular tooth cleaning must be performed using a soft toothbrush, at least two or three times a day.

You may also experience alteration or loss of taste, but this is a temporary side effect that disappears shortly after the end of chemotherapy.

Reduction of liver function

Treatment with carboplatin may lead to a temporary reduction in liver function, which however should return to normal at the end of therapy. In any case, patients are constantly monitored to monitor liver activity before, during and after drug administration.

Amenorrhea

Carboplatin therapy may cause interruption of the menstrual cycle ( amenorrhea ). Consequently, typical symptoms of pre-menopause could occur, such as, for example, hot flushes, excessive sweating and vaginal dryness. These symptoms usually disappear after treatment has ended.

Cardiovascular disorders

These side effects occur very rarely and consist of an increase in blood pressure, stroke, heart failure and / or blood clots .

Other side effects

Other side effects that carboplatin can induce are:

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

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

Furthermore, in some cases, a secondary tumor may occur but this type of adverse effect occurs very rarely.

Since carboplatin is administered intravenously, damage may occur at the site of administration, such as, for example, redness, swelling, pain or leakage of fluid from the cannula during administration.

Action mechanism

Carboplatin is an alkylating agent and is able to form bonds with the two strands that make up DNA.

DNA consists of four fundamental units called nitrogenous bases, these molecules are cytosine, thymine, adenine and guanine.

Carboplatin performs its cytotoxic action in a manner similar to that of its cisplatin precursor; therefore, it acts by binding to a nitrogen atom present in the guanine structure. However, it appears that carboplatin is also capable of forming covalent bonds (ie strong bonds that do not break easily) 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 called apoptosis .

Mode of Use - Posology

Carboplatin is administered by intravenous infusion (drip infusion); it appears as a clear solution that can be colorless or pale yellow.

It can be administered through three different routes:

  • Through a cannula (a thin tube) that is inserted into a vein of an arm or hand;
  • Through a central venous catheter that is inserted subcutaneously into a vein near the clavicle;
  • Through the PICC ( Peripherally Inserted Central Catheter ) line, 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 chemotherapy regimens.

The usual dose of carboplatin for adults is 400 mg / m2, given as a single intravenous dose over a period of 15 to 60 minutes.

The use of carboplatin in children is not recommended.

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

In the event that the patient suffers from renal dysfunction, it is necessary to decrease the amount of drug administered.

In the event of an overdose of carboplatin there is no antidote: the oncologist will have to stop the therapy and adequately treat the symptoms that derive from taking too much of the drug.

Pregnancy and breastfeeding

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

Women should not breast-feed during treatment with carboplatin.

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

Patients - both male and female - and their corresponding 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.

Male patients at a young age may experience sterility following carboplatin therapy. Infertility is not always a reversible side effect, sometimes it becomes permanent.

Contraindications

The use of carboplatin is contraindicated in the following cases:

  • Known hypersensitivity to carboplatin or other platinum-based compounds;
  • During breastfeeding;
  • Presence of serious problems and / or renal dysfunction;
  • Presence of damage and / or dysfunction of the bone marrow.

Particular attention should be paid to the administration of carboplatin to elderly patients over 65 years of age.