Melphalan

Structural formula
General
Non-proprietary name	Melphalan
other names	(2 S ) -2-Amino-3- {4- [bis (2-chloroethyl) amino] phenyl} propanoic acid ( IUPAC ) ( S ) -3- {4- [bis (2-chloroethyl) amino] phenyl} alanine L-PAM Sarcolysin
Molecular formula	C 13 H 18 Cl 2 N 2 O 2
External identifiers / databases
CAS number 148-82-3 EC number 205-726-3 ECHA InfoCard 100.005.207 PubChem 460612 ChemSpider 405297 DrugBank DB01042 Wikidata Q2298283
Drug information
ATC code	L01 AA03
Drug class	Cytostatic
Mechanism of action	Alkylans
properties
Molar mass	305.2 g · mol -1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 300-310-330-350-361 P: 201-260-264-280-284-302 + 350
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Melphalan (trade name Alkeran; manufacturer Aspen Pharma ) is a drug from the group of cytostatics . The substance is approved for the chemotherapeutic treatment of multiple myeloma and advanced ovarian cancer, but is also used in various other cancers.

Chemically, melphalan is a phenylalanine derivative of mechlorethamine .

Mechanism of action

Melphalan is an alkylant from the group of nitrogen mustard compounds (which also includes cyclophosphamide or bendamustine ). These compounds transfer alkyl groups to the DNA base guanine and lead to chemical bonds between the DNA strands. Nucleic acids modified in this way are prevented from further division and protein biosynthesis by the cell's own mechanisms. These cytotoxic processes take place in all cells, but in particular reduce the multiplication of the rapidly dividing tumor cells.

application

Melphalan can be administered intravenously or orally. The dose used depends on the indication and the kidney function and body weight of the patient. Possibly. the dose must be adjusted individually.

Melphalan is used in multiple myeloma when an initial stem cell transplant is not possible. A combination with other cytostatics such as thalidomide , bortezomib or cyclophosphamide is usually used.

It can also be used for malignant melanoma and AL amyloidosis .

As part of a perfusion of isolated extremities in locally advanced soft tissue sarcomas , melphalan is used in combination with tumor necrosis factor alpha (TNF-α).

Since the drug is only produced by one manufacturer, there were several delivery bottlenecks between 2014 and 2016 .

Side effects

Like most cytostatics, melphalan intake very often results in nausea, vomiting, diarrhea and - in higher doses - hair loss .

Since the active ingredient suppresses the bone marrow , the number of leukocytes and platelets in the blood may decrease during therapy . The possible consequence is the increased occurrence of infections or bleeding.

Melphalan has a mutagenic effect. Therefore, use during pregnancy and breastfeeding is contraindicated . In women, ovarian failure with amenorrhea can result, in men irreversible infertility is possible.

Due to the mutagenic effect, there is also the risk of second malignancies. An increased incidence of acute lymphocytic leukemia and myelodysplastic syndrome has been observed in combination with thalidomide and prednisolone .

Individual evidence

1. ↑ ^{a b} Data sheet melphalan at Sigma-Aldrich , accessed on October 1, 2015 ( PDF ).
2. ↑ DGHO guideline on multiple myeloma. Accessed August 2, 2015.
3. ↑ AWMF guideline ( memento of the original from November 23, 2015 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. to malignant melanoma. Accessed August 14, 2015. 
4. ↑ Dennis L. Kasper, Eugene Braunwald, Anthony S. Fauci, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson: Harrison's Principles of Internal Medicine . 16th edition. McGraw-Hill, New York 2005, pp. 2028 .
5. ↑ Again delivery bottleneck for cancer drug melphalan. In: aerzteblatt.de . May 4, 2016. Retrieved May 26, 2016 . 
6. ↑ Red Hand Letter from Celgene. April 8, 2013, accessed August 2, 2015 . 

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !