Drug intelligence / Profile preview

methotrexate + vinblastine + doxorubicin + cisplatin

Development stage
Phase 3
Lead developer
Bristol Myers Squibb
Modality
Small Molecules
Administration
Intravenous
01

Overview

The combination of methotrexate, vinblastine, doxorubicin, and cisplatin, frequently referred to as MVAC, is a potent multi-agent chemotherapy regimen primarily utilized in the treatment of urothelial carcinoma and bladder cancer. It is employed in neoadjuvant, adjuvant, and metastatic settings. The regimen's efficacy stems from the synergistic actions of its four components: methotrexate, an antimetabolite that inhibits dihydrofolate reductase (DHFR); vinblastine, a vinca alkaloid that disrupts microtubule formation by binding to tubulin; doxorubicin, an anthracycline that intercalates DNA and inhibits topoisomerase II; and cisplatin, a platinum-based agent that forms covalent cross-links with DNA. Together, these agents arrest the cell cycle and induce apoptosis in rapidly dividing cancer cells. While MVAC has historically been a standard of care, it is associated with significant toxicity, leading to the development of the dose-dense (dd-MVAC) schedule and competition from newer regimens like gemcitabine plus cisplatin (GC).

Other names
MVACdd-MVACddMVACdose-dense MVACmethotrexate, vinblastine, adriamycin, and cisplatinmethotrexate + vinblastine + adriamycin + cisplatin
02

Targets

DNATOP2A (DNA topoisomerase II)DHFR (Dihydrofolate reductase)TUBB (Tubulin (alpha and beta subunits))TOP2B (DNA topoisomerase II beta)

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