melphalan

Melphalan is an anticancer drug belonging to the class of alkylating agents.

Performs its cytotoxic action (toxic to cells) damaging the DNA that is indispensable for cellular life; thus causing the death of neoplastic cells.

Therapeutic indications

Melfalan - Chemical Structure

Melphalan is mainly used for the treatment of multiple myeloma, but it is also used for other types of tumors, including:

Ovarian cancer;
Breast cancer;
Soft tissue sarcoma localized in the limbs;
Malignant melanoma located at the extremities;
Ewing's sarcoma;
Infantile neuroblastoma;
Polycythemia vera, also known as PV or Vaquez's disease.

Warnings

Melphalan should only be administered under the strict supervision of physicians specializing in the administration of alkylating agents with antitumor action. In particular, administration at high doses of melphalan intravenously, must take place only in specialized centers and with constant monitoring of the patient.

Since melphalan has an immunosuppressive action (ie suppresses the immune system), the vaccination of patients with live attenuated virus vaccines is not recommended. In fact, vaccination with live viruses in immunosuppressed patients can promote viral replication causing infections and increasing the side effects of the vaccine itself.

In patients taking high doses of melphalan, prophylactic administration of anti-infective agents and, if required, the administration of blood derivatives should be considered. In the period immediately following the administration of the drug it would be good to maintain a high renal glomerular filtrate by means of forced hydration and diuresis .

During treatment with melphalan, direct and prolonged exposure to sunlight is not recommended. In case of exposure, it is good to use sunscreen with a high protection index.

Interactions

The administration of melphalan at high intravenous doses together with nalidixic acid (an antibacterial drug) resulted in death from hemorrhagic enterocolitis in pediatric patients.

Alterations in renal function have been identified in patients treated with high doses of intravenous melphalan who - having received a bone marrow transplant - were treated with ciclosporin to prevent transplant rejection.

During treatment with melphalan it would be better to avoid taking aspirin because - by acting as a blood thinner - it could increase the risk of bleeding.

Interactions with other drugs, such as cimetidine (used to treat gastric ulcer) and steroids may also occur.

It is however necessary to inform your doctor about all the drugs you are taking or have recently taken, even if they are over-the-counter drugs.

Side effects

Melphalan can trigger various side effects. These adverse effects vary depending on the type of tumor to be treated, the amount of drug administered, the route of administration chosen and the patient's condition. Moreover, there is great variability from individual to individual and it is not said that all the side effects occur in all patients with the same intensity.

Below is a list of the main side effects induced by melphalan.

Myelosuppression

Melphalan can induce myelosuppression, ie it is able to suppress bone marrow activity. This suppression causes a reduction in blood cell production which can lead to:

Anemia (decrease in hemoglobin blood levels), the main symptom of the onset of anemia is the feeling of physical exhaustion ;
Leukopenia (decreased white blood cell levels), with increased susceptibility to infection contraction ;
Plateletopenia (decrease in the number of platelets), this leads to the appearance of bruising and abnormal bleeding with an increased risk of bleeding .

Gastrointestinal disorders

Following administration, melphalan may cause nausea, vomiting and diarrhea .

Vomiting can occur from a few hours to a few days after taking the drug. Antiemetic drugs are used to control this symptom. If the symptom persists, it is necessary to inform the oncologist.

Diarrhea can be treated with anti-diarrheal drugs and it is necessary to drink a lot to replenish lost fluids.

Allergic reactions

Allergic reactions may occur following the administration of melphalan, which usually occurs in the form of hives, edema, skin rash and anaphylactic shock . Rarely - following such reactions - can a cardiac arrest occur.

Respiratory disorders

These side effects are rare and consist of interstitial pneumonias and pulmonary fibrosis, in some cases even fatal.

Hepatobiliary disorders

Melphalan can cause liver disorders ranging from impaired liver function tests to clinical manifestations such as hepatitis and jaundice .

Loss of hair and hair

Hair and hair may thin out or fall completely, but it is a reversible side effect. Hair and hair usually begin to grow back a few months after the end of chemotherapy.

Renal disorders

In patients suffering from multiple myeloma with renal damage and treated with melphalan, high levels of urine nitrogen were detected, especially in the initial course of therapy.

Mutagenesis

In patients treated with melphalan, chromosomal aberrations (alterations in the structure of chromosomes) caused by the drug itself have been identified.

Carcinogenesis

It seems that melphalan has leukemogenic power, that is it seems that it is able to induce leukemias. Cases of acute leukemia have been reported following treatment with melphalan for the treatment of diseases such as amyloidosis, malignant melanoma and multiple myeloma.

It has also been noted that in patients with ovarian cancer treated with alkylating agents - including melphalan - there is an increased incidence of acute leukemia compared to treatment with other types of anticancer drugs.

Amenorrhea

The use of melphalan can cause amenorrhea, ie the interruption of the menstrual cycle.

Action mechanism

Melphalan is an alkylating agent and, as such, is able to intercalate alkyl groups within the double DNA strand.

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

In particular, melphalan performs its cytotoxic action by alkylating guanine through the formation of covalent bonds, ie strong bonds that are very difficult to break. The formation of these bonds creates alterations at the level of the DNA, which prevents the cell from dividing causing its death.

Mode of Use - Posology

Melphalan can be used both alone and in combination with other anticancer drugs. It is available for both intravenous and oral administration.

For intravenous administration, it is found in the form of a dry powder that must be dissolved in a special solvent just before the infusion.

For oral administration, melphalan is available as white tablets.

Multiple myeloma

For the treatment of multiple myeloma with intravenous melphalan - when used alone - the usual dose is 0.4 mg / kg of body weight.

For oral administration, however, the usual dose is 0.15 mg / kg of body weight per day, in divided doses for a period of 4 days.

Advanced ovarian cancer

For the treatment of ovarian cancer with intravenous melphalan only, the usual dose is 1 mg / kg body weight, at 4-week intervals.

When, on the other hand, melphalan is used in combination with other cytotoxic drugs, the usual dose is 0.3-0.4 mg / kg of body weight, at 4-6 week intervals.

If melphalan is administered orally, the usual dose is 0.2 mg / kg of body weight for 5 consecutive days; between one cycle and another there must be an interval of 4-8 weeks or in any case an adequate interval for the bone marrow to recover its activity.

Malignant melanoma

Melphalan for intravenous infusion can be used in combination with hyperthermia as an adjuvant therapy to surgery for the treatment of malignant melanomas in the early stage and for palliative treatment of advanced but localized forms.

Soft tissue sarcoma

Intravenous melphalan - in combination with hyperthermia - can be used for the treatment of all stages of soft tissue sarcoma. Generally, this therapy is used in association with surgery.

Advanced neuroblastoma in childhood

For the treatment of this pathology, intravenous melphalan is used. The usual dose is between 100 and 240 mg / m2 of body surface area, in association with hematopoietic stem cell transplantation or in combination with radiotherapy and / or other anticancer drugs.

Advanced breast cancer

Oral melphalan is used to treat this tumor. The usual dose is 0.15 mg / kg of body weight for 5 days, with intervals of 6 weeks between one cycle and another.

Polycythemia vera

Melphalan administered orally is used for polycythemia vera. The usual starting dose is 6-10 mg a day for 5-7 days.

In case of administration of melphalan in elderly patients it is necessary to ensure the patient's condition and, if required, to adjust the dosage of the drug.

Also in the case of patients suffering from renal insufficiency it may be necessary to adjust the dose of drug to be administered.

In any case, the dosage is established by the oncologist according to the pathology to be treated, the route of administration and according to the patient's condition.

Pregnancy and breastfeeding

Adequate precautions must be taken to avoid possible pregnancies during the entire period of treatment with melphalan and for a period ranging from six months to some years after the end of chemotherapy.

The use of melphalan - if possible - should be avoided during pregnancy, especially in the first trimester.

Mothers on melphalan should not breast-feed.

Because of the mutagenic properties it has, there is reason to believe that melphalan can be teratogenic and cause birth defects in the offspring of patients treated with the drug.

In male patients, melphalan therapy can cause sterility, which is not always reversible.