vinblastine + methotrexate

The vinblastine + methotrexate combination is a low-dose chemotherapy regimen primarily used for treating aggressive fibromatosis (desmoid tumors). This combination has shown effectiveness in both adults and children with this condition, particularly for cases that are inoperable, recurrent, or not amenable to radiation or surgery. ## Mechanism of Action Vinblastine is a vinca alkaloid that binds to tubulin, inhibiting the assembly of microtubules. It causes M-phase specific cell cycle arrest by disrupting microtubule assembly and proper formation of the mitotic spindle and kinetochore, which are necessary for chromosome separation during anaphase of mitosis[6][8]. Methotrexate works by blocking cell division through a different mechanism, complementing vinblastine's action. Together, they provide an effective combination therapy that can promote tumor regression or block tumor growth in most patients with desmoid-type fibromatosis[5]. ## Clinical Efficacy Studies have shown that methotrexate plus vinblastine given every 7-10 days for several months is associated with prolonged stable disease in a substantial subset of patients with advanced (inoperable) aggressive fibromatosis[1][3]. In one Phase II study with 30 patients, 40% showed partial response, and 60% had stable disease or minor tumor shrinkage along with symptom relief[1]. In children with desmoid fibromatosis, this combination has demonstrated the ability to promote tumor regression or block tumor growth in most cases[5]. A biweekly administration schedule has also shown similar efficacy to weekly administration, with a clinical benefit rate of 95% and progression-free survival at 5 years of 80.8%[7]. ## Dosing Regimen The typical dosing regimen includes: - Methotrexate: 30 mg/m² per dose - Vinblastine: 5-6 mg/m² per dose These are usually administered intravenously weekly for 6-12 months and then every other week for an additional 6 months[5][9]. Some protocols use a biweekly schedule throughout treatment with similar efficacy[7]. ## Side Effects Common adverse effects include: - Neutropenia (most common toxicity) - Anemia - Nausea and vomiting - Elevations in hepatic transaminases - Fatigue - Mucositis - Myalgia Most adverse effects are reversible with interruption of chemotherapy[5]. The biweekly administration schedule appears to be better tolerated compared to weekly administration[7]. This combination therapy represents an important treatment option for patients with aggressive fibromatosis, particularly when surgery or radiation therapy is not feasible or has been unsuccessful.

Other names

Vinblastine and MethotrexateMethotrexate and Vinblastine combinationVBM regimen