Melphalan - instructions for use, description, pharmacological action, indications for use, dosage and method of use, contraindications, side effects. Medicinal reference book geotar
cytostatic alkylating agent. Blocks mitotic cell division in rapidly proliferating tissues, disrupting DNA synthesis.
Indications for use of the drug Melphalan
Myeloma, ovarian adenocarcinoma (late stages), breast carcinoma (late stages), polycythemia vera, skin melanoma; soft tissue sarcoma of the extremities (when administered by regional perfusion); adjuvant therapy for surgical removal breast carcinoma.
Use of the drug Melphalan
In multiple myeloma, the use of melphalan in combination with prednisolone is more effective than monotherapy. like this combination therapy usually carried out in courses, but the advantages of this technique compared to continuous therapy have not been established. Melphalan is usually prescribed at 0.15 mg/kg per day in divided doses in combination with 40 mg of prednisolone; Duration of treatment is 4 days. The interval between courses of treatment is 6 weeks. Other dosage regimens are also possible. Long-term treatment (more than 1 year) of patients amenable to therapy does not lead to further improvement in results.
For ovarian adenocarcinoma, 0.2 mg/kg per day orally in divided doses 3 times a day for 5 days is usually prescribed. The interval between courses is 4-8 weeks, provided that function is restored by this time bone marrow. Similar results are achieved with an intravenous infusion of 1 mg/kg over 8 hours; the interval between administrations is 4 weeks.
At late stages for breast cancer, melphalan can be administered orally at a dose of 0.2-0.3 mg/kg per day or 6 mg/m2 body surface area per day for 4-6 days; the interval between courses is 3-6 weeks.
At polycythemia vera The dose of melphalan required to achieve remission is usually 6-10 mg/day for 7-10 days. Maintenance dose - 2-4 mg/day. During maintenance therapy, the composition of peripheral blood should be regularly monitored and appropriate dose adjustments should be made.
For melanoma, regional perfusion with melphalan is performed on early stages tumor development as adjuvant therapy for surgical interventions and as palliative therapy in later stages, but with localized forms of the disease. Regional perfusion with melphalan is carried out in the treatment of patients with all stages of localized soft tissue sarcoma, usually in combination with surgical methods treatment. Melphalan is often prescribed in combination with actinomycin D.
Melphalan is extremely rarely prescribed to children; No general recommendations on its use in pediatric practice.
Contraindications to the use of the drug Melphalan
There are no absolute contraindications for taking melphalan (given the vital importance of the indications). Should not be administered to patients who have recently undergone radiotherapy or received other cytotoxic drugs.
Side effects of the drug Melphalan
Myelosuppression occurs most frequently; 30% of patients receiving melphalan experience dyspeptic symptoms (nausea and vomiting), and sometimes diarrhea and stomatitis. Functional disorders digestive tract usually mild and less common with monotherapy than with a combination cytostatic drugs. Sometimes a maculopapular rash and itchy skin, alopecia; possible development pulmonary fibrosis And hemolytic anemia after treatment with melphalan. Immediately after IV administration of melphalan, a life-threatening allergic reaction may develop.
Special instructions for the use of Melphalan
Melphalan is an active cytotoxic agent and should only be used under the supervision of an experienced chemotherapist.
It is necessary to regularly monitor the composition of peripheral blood in order to timely detect myelosuppression and prevent irreversible bone marrow aplasia.
Leukopenia and thrombocytopenia may increase even after stopping treatment, therefore, when the first signs of an abnormal decrease in the number of leukocytes and platelets appear, treatment should be temporarily interrupted.
In patients with moderate or severe renal impairment, the initial dose of melphalan for intravenous administration should be reduced by 50%. Subsequent doses are selected taking into account the parameters of hematological studies. Patients with renal failure during treatment with melphalan should be under medical supervision for early detection uremia.
Melphalan, like other alkylating drugs, has a leukemic effect. Known cases acute leukemia that arose after long-term treatment melphalan for diseases such as amyloidosis, melanoma, macroglobulinemia, ovarian cancer and cold agglutination syndrome. In ovarian cancer, it has been found that the use of alkylating drugs, including melphalan, significantly increases the incidence of acute leukemia. When prescribing melphalan, the risk of leukemia should be weighed against the potential therapeutic effect melphalan.
Melphalan causes suppression of ovarian function in premenopausal women, which leads to a significant increase in the incidence of amenorrhea.
There is no evidence that melphalan has teratogenic properties, but the potential for such effects exists because other alkylating drugs are teratogenic. During pregnancy, melphalan should be avoided if possible, especially in the first trimester. In each individual case, the potential risk to the fetus should be weighed against positive effect for mother's health.
Melphalan drug interactions
Melphalan cannot be used with dextrose solutions.
Melphalan drug overdose, symptoms and treatment
The main manifestation toxic effect melphalan is myelosuppressive. There is no specific antidote. The composition of peripheral blood should be carefully monitored for 2 weeks. If necessary, general supportive therapy and blood transfusions are carried out.
List of pharmacies where you can buy Melphalan:
- Saint Petersburg
Melphalan is an alkylating agent. They damage DNA and have cytotoxic, mutagenic and carcinogenic effects.
Release form, composition and packaging
Available in two types:
- Tablets of 2 and 5 mg. Each blister contains 20 pcs. IN cardboard box there can be from 1 to 3 plates.
- Powder for cooking injection solutions in bottles of 50 mg in a set with a solvent.
The active substance is melphalan. At the tablets Excipients: crospovidone; colloidal silicon dioxide; magnesium stearate; Opadry white. The powder has povidone K12; hydrochloric acid.
Manufacturer
SC Balkan Pharmaceuticals SRL (Balkan Pharmaceuticals) Republic of Moldova.
Indications for use
The medicine is used in combination with prednisolone. Effective in treating and. It was originally created for treatment, but did not show significant effectiveness.
Prescribed for the treatment of common malignant tumors childhood, as well as when:
Contraindications
The drug should not be used in case of individual intolerance, suppressed bone marrow function, or during pregnancy and breastfeeding.
It is prescribed with caution for infections, severe concomitant illnesses, bone marrow infiltration by malignant cells, children and the elderly.
pharmachologic effect
Melphalan causes damage to DNA macromolecules and stops protein synthesis. Cytotoxicity is associated with the blockade of interstrand cross-links in the DNA molecule. Active against any tumor cells.
It has a high selectivity of activity in relation to the cells of oncological formations and lymph nodes.
During treatment, the number of abnormal young cells produced by the bone marrow decreases. After stopping treatment, peripheral blood counts quickly return to normal.
The severity of the cytotoxic effect depends on the dose. With complete death of tumor cells in life important organs irreversible changes are not detected.
Instructions for use of Melphalan
The medicine is administered intravenously over 20 minutes. Intra-arterial, intraperitoneal, or intrapleural perfusion can be performed. The dose is selected individually. It may vary depending on the effect and manifestation side effects.
This approach is appropriate if treatment is underway in combination with cytostatics. 16 mg/sq. m. 1 time every four weeks with monotherapy. Average duration treatment is 1 month.
If kidney function is impaired, the dose is halved. The full dose is prescribed only at a certain level of white blood cells and platelets.
Side effects
Side effects may have different manifestations
| Localization: | Manifestations: |
|---|---|
| Blood | Anemia, thrombocytopenia, neutropenia. |
| Respiratory function | Pulmonary fibrosis. |
| Digestive organs | Nausea, vomiting, mucositis, ulcers, liver dysfunction. |
| Leather | Damage to the dermis, soft tissues, vasculitis, alopecia, skin necrosis. |
| Allergy | Anaphylactic shock. |
| Reproductive organs | Amenorrhea, azoospermia. The effects are dose dependent and may be irreversible. |
| Mutagenicity | Secondary malignant tumors. The relationship with immunosuppressive effects has not been clearly established, but an increased risk is expected with long-term use. |
| Other | Hepatitis, increased 5-hydroxyindoleacetic acid in the urine. |
Overdose
With increased doses of the drug, the following may develop:
- anemia, colitis,
- difficulty swallowing,
- nausea and vomiting.
An infection may accompany these signs. Then there is an increase in body temperature, cough, lower back pain, and difficulty urinating.
One of the manifestations of an overdose is the appearance of ulcers on the oral mucosa.
There is no antidote, hemodialysis and hemoperfusion do not help remove excess. Therefore, peripheral blood parameters are monitored for 3-6 weeks.
special instructions
When working with Melphalan, you must follow the rules for handling skin irritants and toxic substances.
During treatment, a blood test is performed to timely detect bone marrow aplasia and myelosuppression. Leukopenia and thrombocytopenia increase after cessation of treatment.
Therefore, if there is an abnormal decrease in platelets or leukocytes, treatment is interrupted.
There are known cases that occurred after long-term treatment with these drugs. However, there is no information that would confirm that the drug has teratogenic properties.
Drug interactions
This substance should not be used with dextrose solutions. It weakens immunization with live virus vaccines. There is an increase in viral replication and side effects from vaccination.
Melphalan in combination with cyclosporine can cause severe renal failure. In combination with nalidixic acid, children may develop enterocolitis.
Pharmacotherapeutic group L01AA03 - antineoplastic agents. Alkylating compounds.
Main Pharmacological action: bifunctional alkylating compound; There are many intracellular molecules, including DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), resulting in impaired tumor cell or cell division lymphoid tissue and her death.
INDICATIONS: multiple myeloma BNF (recommendation for the use of drugs in the British National Formulary, issue 60) late stages of ovarian cancer BNF (recommendation for the use of drugs in the British National Formulary, issue 60); breast carcinoma (monotherapy or in combination with other drugs) additions to surgical treatment of breast cancer BNF (recommendation for the use of drugs in the British National Formulary, 60 issue) polycythemia vera BNF (recommendation for the use of drugs in the British National Formulary, 60 issue) with administration by regional arterial perfusion - treatment of localized malignant melanoma of the extremities BNF (recommendation for the use of drugs in the British National Formulary, issue 60), localized soft tissue sarcoma of the extremities BNF, in high i/v (introduction) therapeutic doses- treatment of late stages of neuroblastoma in children with BNF.
Directions for use and dosage: when administered orally: multiple myeloma - typical pattern oral administration- 0.15 mg/kg per day in several doses for 4 days, repeat at intervals of 6 weeks BNF (prednisolone is additionally added) prolonging the treatment period for more than one year does not improve the results; ovarian adenocarcinoma (late stages): typical treatment regimen - 0.2 mg / kg per day orally for 5 days, the cycle is repeated every 4-8 weeks BNF or to restore peripheral blood counts breast carcinoma: administered orally at a dose of 0. 15 mg/kg or 6 mg/m2 for 5 days, the cycle is repeated every 6 weeks polycythemia vera: to induce remission, doses of 6-10 mg are used for 5-7 days, after achieving a satisfactory degree of remission, doses of 2-4 mg are prescribed day, for maintenance therapy - 2-6 mg per week BNF, with parenteral use: multiple myeloma (individual others... or in combination with other cytostatics on an intermittent basis) - from 8 mg/m2 to 30 mg/m2 with an interval of 2 to 6 weeks (prednisolone is additionally used) with independent use The standard intravenous (injection) dose is 0.4 mg/kg (16 mg/m2), repeated at the necessary intervals to restore bone marrow function; in high-dose regimens, single intravenous (injection) doses of 100-200 mg/m2 are used (2.5-5.0 mg/kg), but doses exceeding 140 mg/m2 used to protect autologous bone marrow transplantation, in case of renal failure, doses are reduced by 50% since the development of severe myelosuppression is possible, treatment should be carried out in specialized centers; ovarian adenocarcinoma (late stages): when used independently intravenously (injection), the dose is 1 mg/kg (40 mg/m2) with an interval of 4 weeks, with combined use with other cytostatics intravenously (injection) the dose ranges from 0.3 to 0.4 mg / kg (12 -16 mg / m2) with an interval of 4 to 6 weeks hyperthermic regional perfusions: malignant melanoma - used as adjuvant therapy for surgical interventions in the early stages of malignant melanoma and as palliative treatment for advanced but localized forms of the disease; soft tissue sarcoma: used in the treatment of all stages of localized soft tissue sarcoma, usually in combination with surgical treatment methods; late stages of neuroblastoma in children - between 100 and 240 mg/m2 (sometimes divided into three consecutive days) under the protection of autologous bone marrow transplantation alone or in combination with radiation therapy and/or other cytostatics.
Side effects when using drugs: circulatory and lymphatic system- very often bone marrow suppression (leukopenia and thrombocytopenia), rarely hemolytic anemia the immune system- rarely AR ( allergic reactions) (urticaria "Belgorod, swelling, skin rash And anaphylactic shock with repeated intravenous administration) respiratory system: rarely interstitial pneumonitis and pulmonary fibrosis (including fatal cases) Gastrointestinal tract ( gastrointestinal tract) - very often nausea, vomiting and diarrhea, stomatitis at high doses. rarely stomatitis with usual doses: hepatobiliary system - rarely from violation of liver function tests in clinical manifestations hepatitis and jaundice, skin and subcutaneous tissue - often alopecia, rarely maculopapular rash and itching of the kidneys and urinary tract- often a temporary increase in urea levels in the early stages of therapy was observed in patients with myeloma who had kidney damage.
Contraindications to the use of drugs: hypersensitivity to the drug.
Drug release forms: powder for preparation of solution for injection 50 mg tab. (Tablets), film-coated, 2 mg, 5 mg
Visamodia with other drugs
Vaccines containing killed viruses - the effect of vaccination may be weakened when used simultaneously; vaccines containing live viruses - viral replication may be potentiated and there may be an increase in the side effects associated with the use of the vaccine; nalidoxic acid - the use of high doses of IV melphalan with nalidoxic acid can be fatal due to the occurrence of hemorrhagic enterocolitis; cyclosporine - high doses of IV melphalan when used with cyclosporine in patients after bone marrow transplantation can lead to impaired renal function
Features of use in women during pregnancy and lactation
Pregnancy If possible, avoid use, especially in the 1st trimester. The potential danger to the fetus must be comparable to the expected benefit to the mother
Lactation: Contraindicated.
Features of use for insufficiency of internal organs
Dysfunction of the cerebrovascular system: No special recommendations
Dysfunction of the liver: Prescribe with caution.
Renal dysfunction Reducing the dose.
Dysfunction respiratory system:
No special recommendations
Features of use in children and the elderly
children under 12 years old In high injectable doses it is used to treat childhood neuroblastoma, doses are calculated depending on body surface area. It is used very rarely in normal doses, so there are no general dosage recommendations.
Elderly faces and old age:
Application experience is limited. When prescribing high doses, a thorough examination of the patient's functional state is necessary.
Application measures
Information for the doctor: A strong myelosuppressive agent, essential has a blood picture checked to prevent excessive myelosuppression and the risk of irreversible bone marrow aplasia. The blood cell count may continue to decrease after treatment is stopped, so at the first sign of an excessive decrease in the white blood cell or platelet count, stop treatment temporarily. Use with caution in patients who have recently undergone radiation therapy or chemotherapy due to increased toxicity to the bone marrow. Immunization with vaccines containing live microorganisms can lead to infectious complications in immunocompromised patients; immunization with these vaccines is not recommended. Injections cause damage soft tissue around the vessels when the drug enters extravasally, therefore it is not injected into a peripheral vein. It is recommended to slowly introduce the drug into the system with intravenous infusion through a separate port or by catheterization of the central veins. When prescribing high doses of injectable melphalan, decide on the prophylactic administration of anti-infective drugs, and, if necessary, blood products. You need to make sure there is adequate functional state patient. The solution should be prepared at room t0 by dissolving the lyophilized powder in the solvent provided. Add 10 ml of this substance at a time and immediately begin to shake the bottle vigorously. (Bottle) until completely dissolved. The resulting solution contains the equivalent of 5 mg/ml anhydrous melphalan and a pH of approximately 6.5. The solution has limited stability and must be prepared immediately before use. All unused area should be poured out. Ready district Do not freeze as this may cause precipitation. If the drug is administered at room temperature (approximately 25 ° C), the total time from preparing the solution for injection to completion of the infusion should not exceed 1.5 hours (Time) If any visible signs turbidity or crystallization, the drug should be discarded.
Patient Information: Use under the supervision of a physician experienced in the use of anticancer chemotherapy drugs. Therapy should only be carried out when properly established diagnosis. Women of childbearing age should use reliable contraception. If the solution gets on your skin, you must immediately wash the area thoroughly with soap and big amount cold water. If the solution gets into your eyes, you should immediately rinse them with sodium chloride solution and immediately consult a doctor. If sodium pH There is no chloride, a large volume of water can be used.
in a dark glass bottle 25 pcs.; 1 bottle in a box.
in a bottle 10 ml; complete with solvent (10 ml bottle) or 10 ml bottle; 1 bottle in a plastic pencil case.
pharmachologic effect
pharmachologic effect- cytostatic, antitumor.Pharmacodynamics
Covalently binds (alkylates) carbon intermediates formed from two bis−2-chloroethyl groups to the 7-nitrogen of guanine in DNA. Due to the formation of cross-links in the DNA molecule, it causes disruption of cell division, leading to their death.
Pharmacokinetics
When the drug is administered orally, the time of initial appearance of melphalan in plasma varies from 0 to 336 minutes. Cmax ranges from 70 to 630 ng/ml. Final T1/2 from plasma - 90±57 min. Within 24 hours, 11% of the dose is found in the urine.
With a single bolus administration of Alkeran in doses of 0.5-0.6 mg/kg, the combined initial and final T1/2 were 7.7±3.3 minutes and 108±20.8 minutes, respectively. After injection, monohydroxymelphalan and dihydroxymelphalan were detected in plasma; their concentrations reached a maximum after approximately 60 and 105 min, respectively.
Indications of the drug Alkeran ®
Multiple myeloma, ovarian adenocarcinoma, breast carcinoma, polycythemia vera, localized malignant melanoma and soft tissue sarcoma of the extremities, neuroblastoma (in children).
Contraindications
Pregnancy.
Side effects
Myelodepression (leukopenia, thrombocytopenia, anemia), dyspepsia (nausea, vomiting, diarrhea), stomatitis, allergic rash, itching, baldness, hyperuricemia; rarely: pulmonary fibrosis, hemolytic anemia, in women (during menopause) - suppression of ovarian function.
Interaction
Increases the likelihood of renal dysfunction in bone marrow transplant patients receiving cyclosporine to prevent graft-versus-host disease. Concomitant use with nalidixic acid and cyclosporine should be avoided. In children, incompatible (iv) with nalidixic acid - possible death as a consequence of hemorrhagic enterocolitis.
Directions for use and doses
Method of administration and dose.Inside, intravenously, intravenously. Alkeran should be prescribed only by doctors who have experience in treating malignant neoplasms with cytotoxic drugs. When taking the tablet, do not split it into parts. Absorption of melphalan after oral administration is variable. If necessary, the dose can be gradually increased until signs of myelosuppression appear in order to ensure therapeutic concentrations of the drug. Alkeran solution for injection is prescribed intermittently, both as monotherapy and in combination with other cytotoxic agents. Some treatment regimens additionally include prednisolone. More detailed diagrams treatments are given in the specialized literature.
Multiple myeloma: inside- 0.15 mg/kg/day in several doses for 4 days, the interval between courses is 6 weeks; IV- from 8 to 30 mg/m2 with breaks of 2-6 weeks (when combined with cytostatics) or 0.4 mg/kg (16 mg/m2) once every 4 weeks with monotherapy (repeated administration is carried out subject to recovery after this period of peripheral blood parameters). High-dose therapy - a single intravenous injection of 100 to 200 mg/m2 (2.5-5.0 mg/kg). After using the drug in doses exceeding 140 mg/m2, an autologous bone marrow transplant is necessary. In case of renal failure, the dose of the drug must be reduced by 50%.
Ovarian adenocarcinoma: inside- 0.2 mg/kg/day for 5 days, the course is repeated every 4-8 weeks or as bone marrow function is restored. IV, with monotherapy - 1 mg/kg (approximately 40 mg/m2) at intervals of 4 weeks. When combined with cytostatics - 0.3-0.4 mg/kg (12-16 mg/m2) at intervals of 4-6 weeks.
Polycythemia vera: inside- 6-10 mg/day for 5-7 days (induction of remission), then 2-4 mg/day. Maintenance therapy - 2-6 mg once a week.
Progressive neuroblastoma in children: IV- 100-240 mg/m2 (sometimes the dose is administered in 3 doses over 3 days) both in monotherapy and in combination with radiation therapy and/or other cytostatics, under the protection of autologous bone marrow.
Malignant melanoma: v/a, hyperthermic regional perfusion of Alkeran solution is used as adjuvant therapy for malignant melanoma at an early stage of the disease, as well as palliative care in later stages with a localized form. detailed information on the perfusion technique and recommended doses are given in the specialized literature.
Soft tissue sarcoma: v/a, hyperthermic regional perfusion of Alkeran solution is used for localized form, usually in combination with surgical treatment, at all stages of the disease. It is also possible to prescribe in combination with actinomycin D. Detailed information on the perfusion technique and recommended doses is given in the specialized literature.
Use in children: Alkeran solution in high doses under the protection of autologous bone marrow is used in children with neuroblastoma. The drug in standard doses is indicated only in in rare cases Therefore, data on recommended doses cannot be given.
Use in the elderly: before using the drug in high doses, you should ensure the adequacy of general condition and functions internal organs.
Use for renal failure: if Alkeran solution for injection is used in standard doses (8-40 mg/m2), in patients with moderate and severe renal failure it is recommended to reduce the initial dose by 50%, and then adjust it depending on the degree of inhibition bone marrow functions. For high-dose therapy (100-240 mg/m2), the need for dose reduction depends on the degree of renal impairment, treatment goals, and whether autologous bone marrow stem cells are infused. As a rule, in case of moderate and severe renal failure (creatinine clearance - 30-50 ml/min), the dose of the drug is reduced by 50%. It is also necessary to administer a sufficient amount of fluid and forceful diuresis. For patients with more severe renal failure (Cl creatinine< 30 мл/мин) назначать высокие дозы Алкерана не рекомендуется.
Rules for preparing Alkeran solution for injection
The solution is prepared at room temperature immediately before use (has limited stability) by mixing the lyophilized powder with the solvent supplied with the Alkeran bottle. Add 10 ml of solvent (at once) to the bottle with lyophilized powder and shake vigorously until completely dissolved. The resulting solution contains 5 mg anhydrous melphalan per ml and has a pH of about 6.5. The prepared solution cannot be stored in the refrigerator, because this causes sediment to form.
Rules for administering Alkeran solution for injection
The solution is used only for intravenous administration, except in cases where regional arterial perfusion is indicated. When administered intravenously, it is recommended to administer the Alkeran solution slowly against the background of a rapid infusion of another solution. It is recommended to dilute the Alkeran solution only with 0.9% sodium chloride solution for injection; it should not be mixed with solutions containing dextrose. The stability of Alkeran solution for injection decreases with its further dilution in infusion solution, as well as with increasing temperature environment. At room temperature (approximately 25 °C), the total time from the moment of preparation of the Alkeran solution for injection to the completion of its infusion should not exceed 1.5 hours. If turbidity or crystallization appears in the prepared or diluted Alkeran solution, it should be destroyed. Extravasation should be avoided during administration. In case of difficult access to peripheral veins, the drug is injected into the central veins. High doses Alkeran is recommended to be administered into the central veins. When using the drug for regional arterial perfusion, it is recommended to familiarize yourself with the details of the technique in the specialized literature.
Precautionary measures
Prescribe with caution to patients who have recently undergone radiation and chemotherapy, with impaired renal function. Breastfeeding mothers should stop breast-feeding. Treatment is carried out under the control of the peripheral blood picture and should be temporarily discontinued if there is a threat of excessive myelosuppression and irreversible bone marrow aplasia. As a rule, after its discontinuation, the number of leukocytes and platelets continues to decrease for some time. In patients with severe and moderate renal impairment, the initial dose for intravenous administration should be reduced by 50%, subsequent doses are determined based on the response of peripheral blood. Due to variable absorption after oral administration, dosage should be increased cautiously until myelosuppression occurs, indicating that potential therapeutic concentrations have been achieved.
Storage conditions for the drug Alkeran ®
In a place protected from light, at a temperature not exceeding 30 °C.Keep out of the reach of children.
Shelf life of the drug Alkeran ®
lyophilisate for the preparation of a solution for intravascular administration 50 mg - 3 years.
film-coated tablets 2 mg - 2 years.
film-coated tablets 2 mg - 2 years.
Do not use after the expiration date stated on the package.
Synonyms of nosological groups
| Category ICD-10 | Synonyms of diseases according to ICD-10 |
|---|---|
| C43 Malignant melanoma of the skin | Disseminated malignant melanoma |
| Malignant melanoma | |
| Localized malignant melanoma | |
| Localized form of malignant melanoma | |
| Melanoma | |
| Melanoma after surgical resection | |
| Metastatic form of malignant melanoma | |
| Metastatic melanoma | |
| Advanced metastatic malignant melanoma | |
| C50 Malignant neoplasms of the breast | Hormone-dependent form of recurrent breast cancer in menopausal women |
| Hormone-dependent breast cancer | |
| Disseminated breast carcinoma | |
| Disseminated breast cancer | |
| Disseminated breast cancer with HER2 overexpression | |
| Malignant breast tumor | |
| Malignant neoplasm mammary gland | |
| Breast carcinoma | |
| Contralateral breast cancer | |
| Locally advanced or metastatic breast cancer | |
| Locally advanced breast cancer | |
| Locally recurrent breast cancer | |
| Metastatic breast carcinoma | |
| Metastases of breast tumors | |
| Metastatic breast carcinoma | |
| Inoperable breast carcinoma | |
| Inoperable breast cancer | |
| Breast tumors | |
| Breast cancer in women with metastases | |
| Breast cancer in men with metastases | |
| Breast cancer | |
| Cancer mammary glands in men | |
| Mammary cancer | |
| Breast cancer with distant metastases | |
| Postmenopausal breast cancer | |
| Breast cancer is hormone dependent | |
| Breast cancer with local metastases | |
| Breast cancer with metastases | |
| Breast cancer with regional metastases | |
| Breast cancer with metastases | |
| Nipple and areola cancer | |
| Common hormone-dependent forms of breast cancer | |
| Advanced breast cancer | |
| Recurrent breast cancer | |
| Recurrence of breast tumors | |
| RMJ | |
| Estrogen-dependent breast cancer | |
| Estrogen-dependent breast cancer | |
| C56 Malignant neoplasm of the ovary | Ovarian adenocarcinoma pseudomucinous |
| Germ cell tumor of the ovary | |
| Germ cell tumor of the ovaries | |
| Malignant ovarian tumor | |
| Mucinous ovarian carcinoma | |
| Ovarian carcinoma | |
| Metastatic malignant tumor ovaries | |
| Metastatic ovarian carcinoma | |
| Metastatic ovarian cancer | |
| Metastatic ovarian cancer | |
| Ovarian tumor | |
| Cancer from pseudomucinous cyst | |
| Ovarian cancer | |
| Ovarian cancer | |
| Advanced metastatic ovarian cancer | |
| Advanced ovarian cancer | |
| Trophoblastic tumors | |
| Chorionic carcinoma | |
| Cystadenocarcinoma of the ovary, mucinous | |
| Ovarian cystocarcinoma pseudomucinous | |
| Epithelial tumor of the ovaries | |
| C71 Malignant neoplasm of the brain | Pineal adenoma |
| Anaplastic astrocytoma | |
| Astrocytoma | |
| Glioblastoma | |
| Glioma sarcomatous | |
| Granuloblastoma | |
| Malignant glioma | |
| Malignant brain tumor | |
| Metastatic brain tumors | |
| Brain metastases | |
| Neurolemmoma | |
| Neuroblastoma | |
| Neuroglioma embryonal | |
| Neurospongioblastoma | |
| Neurospongioma | |
| Oligodendroglioma | |
| Oligodendrocyteoma | |
| Tumors of the cerebral hemispheres | |
| Brain tumors | |
| Brain tumors | |
| A brain tumor | |
| Brain tumor | |
| Primary malignant brain tumor | |
| Primary brain tumor | |
| Pinealoma | |
| Brain cancer | |
| Spheroblastoma | |
| Fibroblastoma perineural | |
| Chemodectoma | |
| Choroid papilloma | |
| Choroidepithelioma | |
| Schwannoglioma | |
| Schwannoma | |
| Ependymoma | |
| C92 Myeloid leukemia[myeloid leukemia] | Ph-positive chronic myeloid leukemia |
| Induction of remission in APML | |
| Granulocytic leukemia | |
| Myeloblastic leukemia | |
| Myeloid leukemias | |
| Myeloid leukemia | |
| Myeloid leukemia | |
| Myeloma | |
| Neuroleukemia | |
| Acute myeloblastic leukemia | |
| Acute non-lymphoblastic leukemia | |
| Acute nonlymphoblastic leukemia in adults | |
| Refractory acute nonlymphoblastic leukemias | |
| Subleukemic myelosis | |
| Transformation of preleukemia | |
| C95 Leukemia of unspecified cell type | Leukemia undifferentiated |
| Non-lymphocytic leukemia | |
| Undifferentiated leukemia | |
| Non-lymphocytic leukemia | |
| Acute leukemia in adults | |
| Acute nonlymphocytic leukemia |
Cytostatic alkylating agent. Blocks mitotic cell division in rapidly proliferating tissues, disrupting DNA synthesis.
Indications
Myeloma, ovarian adenocarcinoma (late stages), breast carcinoma (late stages), polycythemia vera, skin melanoma; soft tissue sarcoma of the extremities (when administered by regional perfusion); adjuvant therapy for surgical removal of breast carcinoma.
Application
In multiple myeloma, the use of melphalan in combination with prednisolone is more effective than monotherapy. Such combination therapy is usually carried out in courses, but the advantages of this technique compared to continuous therapy have not been established. Melphalan is usually prescribed at 0.15 mg/kg per day in divided doses in combination with 40 mg of prednisolone; Duration of treatment: 4 days. Interval between courses of treatment 6 weeks. Other dosage regimens are also possible. Long-term treatment (more than 1 year) of patients amenable to therapy does not lead to further improvement in results.
For ovarian adenocarcinoma, 0.2 mg/kg per day orally in divided doses 3 times a day for 5 days is usually prescribed. The interval between courses is 48 weeks, provided that bone marrow function is restored by this time. Similar results are achieved with an intravenous infusion of 1 mg/kg over 8 hours; the interval between administrations is 4 weeks.
For advanced stages of breast cancer, melphalan can be administered orally at a dose of 0.2-0.3 mg/kg per day or 6 mg/m 2 body surface area per day for 4-6 days; the interval between courses is 36 weeks.
For polycythemia vera, the dose of melphalan required to achieve remission is usually 6 x 10 mg/day for 7 x 10 days. Maintenance dose 24 mg/day. During maintenance therapy, the composition of peripheral blood should be regularly monitored and appropriate dose adjustments should be made.
In melanoma, regional perfusion with melphalan is carried out in the early stages of tumor development as adjuvant therapy during surgical interventions and as palliative therapy in later stages, but with localized forms of the disease. Regional perfusion with melphalan is performed in the treatment of patients with all stages of localized soft tissue sarcoma, usually in combination with surgical treatment methods. Melphalan is often prescribed in combination with actinomycin D.
Melphalan is extremely rarely prescribed to children; there are no general recommendations for its use in pediatric practice.
Contraindications
There are no absolute contraindications for taking melphalan (given the vital importance of the indications). Should not be administered to patients who have recently undergone radiotherapy or received other cytotoxic drugs.
Side effects
Myelosuppression occurs most frequently; 30% of patients receiving melphalan experience dyspeptic symptoms (nausea and vomiting), sometimes diarrhea and stomatitis. Dysfunction of the digestive tract is usually mild and occurs less frequently with monotherapy than with a combination of cytostatic drugs. Sometimes maculopapular rash and skin itching, alopecia are observed; The development of pulmonary fibrosis and hemolytic anemia is possible after treatment with melphalan. Immediately after IV administration of melphalan, a life-threatening allergic reaction may develop.
special instructions
Melphalan is an active cytotoxic agent and should only be used under the supervision of an experienced chemotherapist.
It is necessary to regularly monitor the composition of peripheral blood in order to timely detect myelosuppression and prevent irreversible bone marrow aplasia.
Leukopenia and thrombocytopenia may increase even after stopping treatment, therefore, when the first signs of an abnormal decrease in the number of leukocytes and platelets appear, treatment should be temporarily interrupted.
In patients with moderate or severe renal impairment, the initial dose of melphalan for intravenous administration should be reduced by 50%. Subsequent doses are selected taking into account the parameters of hematological studies. Patients with renal impairment should be monitored by a physician during treatment with melphalan for early detection of uremia.
Melphalan, like other alkylating drugs, has a leukemic effect. There are known cases of acute leukemia that occurred after long-term treatment with melphalan for diseases such as amyloidosis, melanoma, macroglobulinemia, ovarian cancer and cold agglutination syndrome. In ovarian cancer, it has been found that the use of alkylating drugs, including melphalan, significantly increases the incidence of acute leukemia. When prescribing melphalan, the risk of leukemia should be weighed against the potential therapeutic effect of melphalan.
Melphalan causes suppression of ovarian function in premenopausal women, which leads to a significant increase in the incidence of amenorrhea.
There is no evidence that melphalan has teratogenic properties, but the potential for such effects exists because other alkylating drugs are teratogenic. During pregnancy, melphalan should be avoided if possible, especially in the first trimester. In each individual case, the potential risk to the fetus should be weighed against the positive effect on the health of the mother.
Interactions
Melphalan cannot be used with dextrose solutions.
Overdose
The main manifestation of the toxic effect of melphalan is myelosuppression. There is no specific antidote. The composition of peripheral blood should be carefully monitored for 2 weeks. If necessary, general supportive therapy and blood transfusions are carried out.
