Cyclophosphamide + Fluorouracil + Homoharringtonine + Methotrexate

This is a four-drug chemotherapy regimen combining cyclophosphamide, fluorouracil, homoharringtonine (also known as omacetaxine mepesuccinate), and methotrexate. Each agent targets cancer cells through distinct mechanisms: 1. **Homoharringtonine/Omacetaxine mepesuccinate**: A plant alkaloid derived from *Cephalotaxus fortunei* that functions as a protein synthesis inhibitor. It binds to the ribosome and prevents protein translation. It was approved by the FDA in 2012 for treating chronic myeloid leukemia (CML) after failure of two or more tyrosine kinase inhibitors, though its approval in the US was discontinued as of August 2024. 2. **Cyclophosphamide**: An alkylating agent that cross-links DNA, preventing cell division. 3. **Fluorouracil (5-FU)**: An antimetabolite that interferes with DNA synthesis by inhibiting thymidylate synthase. 4. **Methotrexate**: A folate antagonist that inhibits dihydrofolate reductase, preventing DNA synthesis and cell division. Pharmacokinetics specific to homoharringtonine (from the provided text): Maximum concentration is reached after about 30 minutes. Its steady state volume of distribution is 141 ± 93.4 L, and protein binding is equal to or less than 50%. It undergoes little hepatic metabolism, being mostly metabolized to 4'-DMHHT by plasma esterase hydrolysis. Renal elimination is less than 15%, and its half-life is approximately 6 hours after subcutaneous administration. This combination regimen likely targets hematological malignancies, given homoharringtonine's established efficacy in CML and demonstrated effectiveness in T-cell acute lymphoblastic leukemia (T-ALL), coupled with the broad utility of the other components in various cancer treatments. The development history of homoharringtonine is notable for its long development period (approximately 40 years) from its first description in 1970 to its FDA approval in 2012. When combined, the regimen would likely have significant adverse effects, including severe myelosuppression, bleeding, hyperglycemia, and potential fetal harm, necessitating careful monitoring and supportive care.

Other names

CFHM (possible abbreviation)