Cyclophosphamide, Vincristine, Prednisone incorporates cyclophosphamide (Bristol-Myers Squibb’s Cytoxan, Baxter’s Endoxan/Endoxana, Pfizer’s Neosar/Cyclostin, generics), vincristine (Eli Lilly’s Oncovin), and prednisone (generics). As with CHOP, this older regimen is losing favor to fludarabine-based regimens.
Mechanism of Action
• Cyclophosphamide is an alkylating agent. These agents alkylate DNA bases, thereby producing “cross-links” that covalently link the two DNA strands and prevent cell replication
• Vincristine is a vinca alkaloid. Vinca alkaloids interact with tubulin and disrupt microtubular function in the mitotic spindle. This action leads to metaphase arrest, resulting in mitotic arrest and cell death.
• Prednisone is a corticosteroid and reduces inflammatory responses and suppresses the immune system.
The majority of randomized trials comparing Cyclophosphamide, Vincristine, Prednisone (also known as COP) treatment with chlorambucil as first-line therapy report equivalent response rates with the two treatment strategies. An Eastern Cooperative Oncology Group (ECOG) study randomized patients with advanced chronic lymphocytic leukemia to receive either chlorambucil and prednisone or Cyclophosphamide, Vincristine, Prednisone. A median follow-up of seven years determined that chlorambucil/prednisone and Cyclophosphamide, Vincristine, Prednisone invoked no significant differences in survival (4.8 versus 3.9 years), CR rate (25% versus 23%), and duration of response (2.0 versus 1.9 years). These results were also comparable to those obtained using the CHOP regimen.
The French Cooperative Group on chronic lymphocytic leukemia obtained similar results in an analysis of 291 Binet stage B patients, randomized to receive either chlorambucil or Cyclophosphamide, Vincristine, Prednisone (French Cooperative Group on chronic lymphocytic leukemia, 1990). No significant differences were observed either in the three- and five-year survival rates (69% and 44% in the chlorambucil group and 73% and 43% in the Cyclophosphamide, Vincristine, Prednisone group, respectively) or in median survival times (58 months versus 57 months, respectively).
A large-scale meta-analysis of 2,022 chronic lymphocytic leukemia patients in ten trials confirmed that the combination chemotherapy regimens Cyclophosphamide, Vincristine, Prednisone and CHOP offer no benefit in long-term survival when compared with chlorambucil and were significantly more toxic (chronic lymphocytic leukemia Trialists’ Collaborative Group, 1999).