Cyclophosphamide

Cyclophosphamide (the generic name for Cytoxan, Neosar), also known as cytophosphane, is a chemotherapeutic activity.

Uses

The main use of cyclophosphamide is together with other chemotherapy agents in the treatment of lymphomas, some forms of leukemia and some solid tumors. It is a chemotherapy drug that works by slowing or stopping cell growth. It also works by decreasing the immune system's response to various diseases.

In addition, its use is becoming more common in autoimmune diseases where MMF from cyclophosphamide.

It is also used to treat Minimal Change Disease and rheumatoid arthritis. It is still used for Wegener's granulomatosis. The trade name is Endoxan.

Pharmacokinetics/Pharmacodynamics

Cyclophosphamide is converted by mixed function Mesna.

Recent clinical studies have shown that cyclophosphamide induce beneficial immunomodulatory effects in the context of adoptive immunotherapy. Although the mechanisms underlying these effects are not fully understood, several mechanisms have been suggested based on potential modulation of the host environment, including^{[citation needed]}:

1. Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts
2. Induction of T cell growth factors such as type I IFNs, and/or
3. Enhanced grafting of adoptively transferred tumor-reactive effector T cells by the creation of an immunologic space niche.

Thus, cyclophosphamide pre-conditioning of recipient hosts (for donor T cells) has been used to enhance immunity in naïve hosts, and to enhance adoptive T cell immunotherapy regimens as well as active vaccination strategies, inducing objective anti-tumor immunity.

Mode of action

The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. This metabolite is only formed in cells which have low levels of ALDH.

Phosphoramide mustard forms DNA crosslinks between (interstrand crosslinkages) and within (intrastrand crosslinkages) DNA strands at guanine N-7 positions. This leads to cell death.

Cyclophosphamide has relatively little typical chemotherapy toxicity as ALDHs are present in relatively large concentrations in bone marrow stem cells, liver and intestinal epithelium. ALDHs protect these actively proliferating tissues against toxic effects phosphoramide mustard and acrolein by converting aldophosphamide to carboxyphosphamide that does not give rise to the toxic metabolites (phosphoramide mustard and acrolein).

Side-effects

Many people taking cyclophosphamide do not have serious side effects. acrolein.

Cyclophosphamide is itself carcinogenic, potentially causing transitional cell carcinoma of the bladder as a long-term complication. It can lower the body's ability to fight an infection. It can cause temporary or (rarely) permanent sterility. Although it is used to treat cancer, it may increase the risk of developing another form of cancer, sometimes months to years after treatment.

Other (serious) side effects include:

• pink/bloody urine,
• unusual decrease in the amount of urine,
• mouth sores,
• unusual tiredness or weakness,
• joint pain,
• easy bruising/bleeding,
• stopping of menstrual periods,
• existing wounds that are slow healing.

History

Cyclophosphamide and the related enzymatically converted into the active, toxic form. The first clinical trials were published at the end of the 1950s.^[2][3][4]

References