MELPHALAN - MEDICATIONS

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Melphalan

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

It carries out its cytotoxic action (toxic to cells) by damaging the DNA which is essential for cellular life; thus causing the death of the neoplastic cells.

Therapeutic indications

Melphalan - Chemical Structure

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

Ovarian carcinoma;
Breast cancer
Soft tissue sarcoma localized in the limbs;
Malignant melanoma localized in 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 close supervision of physicians specialized in the administration of alkylating agents with antitumor action. In particular, the administration of high doses of intravenous melphalan should only take place in specialized centers and with constant monitoring of the patient.

Since melphalan has an immunosuppressive action (i.e. suppresses the immune system), vaccination of patients with live attenuated virus vaccines. 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, the prophylactic administration of anti-infective agents and, if required, the administration of blood derivatives. In the period immediately following the administration of the drug it would be good to maintain an elevated renal glomerular filtrate by means of hydration and forced diuresis.

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

Interactions

The administration of high-dose intravenous melphalan concomitantly with the intake of nalidixic acid (an antibacterial drug) resulted in death from hemorrhagic enterocolitis of pediatric patients.

Renal function changes have been identified in patients treated with high doses of intravenous melphalan who - having received a bone marrow transplant - have been treated with cyclosporine for the prevention of rejection of the transplant itself.

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

Interactions with other medications may also occur, such as cimetidine (used for the treatment of gastric ulcer) e steroids.

However, you should tell your doctor about any medications you are taking or have recently taken, even if they are over the counter.

Side effects

Melphalan can trigger a variety of side effects. These adverse effects vary according to the type of tumor to be treated, the amount of drug administered, the route of administration chosen and depending on the patient's condition. Furthermore, there is a great variability from individual to individual and it is not certain that side effects occur in all and 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 the activity of the bone marrow. This suppression causes a reduction in the production of blood cells which can lead to:

Anemia (decrease in blood levels of hemoglobin), the main symptom of the onset of anemia is the sensation of physical exhaustion;
Leukopenia (decrease in white blood cell levels), with increased susceptibility to contraction of infections;
Thrombocytopenia (decrease in the number of platelets), this leads to the appearance of bruises And abnormal bleeding with increased risk of bleeding.

Gastrointestinal disorders

Following administration, melphalan may provoke nausea, He retched And diarrhea.
Vomiting may occur from a few hours to a few days after taking the drug. Antiemetic (antivomiting) drugs are used to control this symptom. If the symptom persists, the oncologist should be informed.
Diarrhea can be treated with antidiarrheal medications and a lot of drinking is required to replenish lost fluids.

Allergic reactions

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

Respiratory pathologies

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

Hepatobiliary disorders

Melphalan can cause liver disorders ranging from abnormal liver function tests to clinical manifestations, such as hepatitis And jaundice.

Hair and hair loss

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

Renal pathologies

High levels of urinary azotaemia have been observed in patients with multiple myeloma with renal impairment and treated with melphalan, especially in the initial course of therapy.

Mutagenesis

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

Carcinogenesis

Melphalan appears to have power leukemogen, that is, it seems to be able to induce leukemia. Cases of acute leukemia have been reported following melphalan therapy for the treatment of conditions such as amyloidosis, malignant melanoma and multiple myeloma.
It was also noted that in ovarian cancer patients 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, that is the interruption of the menstrual cycle.

Mechanism of action

Melphalan is an alkylating agent and, as such, is capable of intercalating alkyl groups within the double strand of DNA.
DNA is made up of four basic units called nitrogenous bases. These fundamental molecules are adenine, thymine, cytosine and guanine.
In particular, melphalan carries out its cytotoxic action by alkylating guanine through the formation of covalent bonds, i.e. strong bonds that are very difficult to break. The formation of these bonds creates alterations in the DNA, which prevents the cell from dividing causing its death.

Method of Use - Dosage

Melphalan can be used either alone or in combination with other anticancer drugs. It is available for both intravenous and oral administration.
For intravenous administration, it comes in the form of a dry powder that must be dissolved in a suitable solvent just prior to infusion.
For oral administration, melphalan is available in the form of white tablets.

Multiple myeloma

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

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

Advanced ovarian cancer

For the treatment of ovarian cancer with intravenous melphalan alone the usual dose is 1 mg / kg body, at 4-week intervals.
On the other hand, when melphalan is used in combination with other cytotoxic drugs, the usual dose is 0.3-0.4 mg / kg of body weight, at intervals of 4-6 weeks.

If melphalan is administered orally, the usual dose is 0.2 mg / kg body weight for 5 consecutive days; between one cycle and the other 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 initial stage and for the palliative treatment of advanced but localized forms.

Soft tissue sarcoma

Intravenous melphalan - in combination with hyperthermia - can be used to treat all stages of soft tissue sarcoma. Generally, this therapy is used in conjunction with surgery.

Advanced neuroblastoma in childhood

Intravenous melphalan is used for the treatment of this pathology. The usual dose is between 100 and 240 mg / m2 of body surface area, in association with haematopoietic 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 6-week intervals between one cycle and the next.

True polycythemia

Orally administered melphalan is used for polycythemia vera. The usual starting dose is 6-10 mg per 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.

Even in the case of patients with renal insufficiency it may be necessary to adjust the dose of the 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 the patient's condition.

Pregnancy and breastfeeding

Adequate precautions should be taken to avoid possible pregnancy throughout the period of treatment with melphalan and for a period ranging from six months to a few 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 therapy should not breastfeed.

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

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