Perfosfamide

Perfosfamide
Clinical data
Other names	Perfosfamide
Routes of; administration	Extracorporal treatment of cellular masses; intravenously
ATC code	L01 ;
Identifiers
	IUPAC name (2S,4S)-N,N-Bis(2-chloroethyl)-4-hydroperoxy-2-oxo-1,3,2λ5-oxazaphosphinan-2-amine;
CAS Number	39800-16-3 ;
PubChem CID	38347;
ChemSpider	35147 ;
UNII	U880A4FUDA;
ChEBI	CHEBI:196991 ;
ChEMBL	ChEMBL61511 ;
CompTox Dashboard (EPA)	DTXSID2049058 ;
Chemical and physical data
Formula	C7H15Cl2N2O4P
Molar mass	293.08 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1COP(=O)(NC1OO)N(CCCl)CCCl;
	InChI InChI=1S/C7H15Cl2N2O4P/c8-2-4-11(5-3-9)16(13)10-7(15-12)1-6-14-16/h7,12H,1-6H2,(H,10,13)/t7-,16-/m0/s1 ; Key:VPAWVRUHMJVRHU-GYKQLYQFSA-N ;
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Perfosfamide, or 4-hydroperoxycyclophosphamide (trade name Pergamid) was an experimental drug candidate for blood cancers that was rejected by the FDA in 1993 and never reached the market.

Intended use

Perfosfamide was used experimentally by oncologists in the 1980s for use in bone marrow transplant procedures for treatment of blood cancers. It was added to the tissue after it had been taken from the donor but before the tissue was administered to the patient to "purge" lymphocytes in order to prevent Graft Versus Host Disease, which results from donor lymphocytes attacking normal host cells and tissues, and to "purge" a patient's own (autologous) collected hematopoietic stem cells of any malignant cells it may still contain at the time of harvesting.^[1]^[2]^: 255

In 1989 Nova Pharmaceutical took over development of the compound and in 1992, it submitted a new drug application to the FDA for using perfosamide to purge malignant cells in transplants for the treatment of acute myeloid leukemia. In the ensuing year, it merged with Scios to become Scios Nova. In March 1993, the FDA's Oncology Drugs Advisory Committee rejected the application because all the data was from the experimental uses, and no randomized clinical trial had been conducted.^[3] At the review meeting, Scios Nova also announced that it would not fund further development of the drug candidate.^[4]

Chemistry

Perfosfamide is an oxazaphosphorine compound, similar to mafosfamide and cyclophosphamide. Like those compounds it, is metabolized to 4-hydroxycyclophosphamide, which eventually gives rise to the two directly cytotoxic metabolites — phosphoramide mustard and acrolein.^[5]

References

^ Sládek NE (August 1999). "Aldehyde dehydrogenase-mediated cellular relative insensitivity to the oxazaphosphorines". Current Pharmaceutical Design. 5 (8): 607–25. doi:10.2174/1381612805666230110215319. PMID 10469894.
^ Colvinn OM (2004). "Chapter 20: Pharmacologic Purging of Bone Marrow.". In Thomas ED, et al. (eds.). Thomas' Hematopoietic Cell Transplantation. Vol. 457. John Wiley & Sons. ISBN 9781405112567.
^ Fox JL (April 1993). "Scios Nova may purge Pergamid after FDA setback". Nature Biotechnology. 11 (4): 439. doi:10.1038/nbt0493-439. S2CID 6110616.
^ "Scios Nova's Pergamid: No Further Trials Will Be Funded". The Pink Sheet. 8 March 1993.
^ Ludeman SM (August 1999). "The chemistry of the metabolites of cyclophosphamide". Current Pharmaceutical Design. 5 (8): 627–43. doi:10.2174/1381612805666230110215458. PMID 10469895.

[1] Sládek NE (August 1999). "Aldehyde dehydrogenase-mediated cellular relative insensitivity to the oxazaphosphorines". Current Pharmaceutical Design. 5 (8): 607–25. doi:10.2174/1381612805666230110215319. PMID 10469894.

[2] Colvinn OM (2004). "Chapter 20: Pharmacologic Purging of Bone Marrow.". In Thomas ED, et al. (eds.). Thomas' Hematopoietic Cell Transplantation. Vol. 457. John Wiley & Sons. ISBN 9781405112567.

[3] Fox JL (April 1993). "Scios Nova may purge Pergamid after FDA setback". Nature Biotechnology. 11 (4): 439. doi:10.1038/nbt0493-439. S2CID 6110616.

[4] "Scios Nova's Pergamid: No Further Trials Will Be Funded". The Pink Sheet. 8 March 1993.

[5] Ludeman SM (August 1999). "The chemistry of the metabolites of cyclophosphamide". Current Pharmaceutical Design. 5 (8): 627–43. doi:10.2174/1381612805666230110215458. PMID 10469895.

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