Fludarabine has shown marked activity in CLL, inducing response in 70% to 80% and 45% to 55% of patients with untreated and relapsed CLL, respectively. Fludarabine combined with cyclophosphamide induced an overall response in 88% of untreated patients (complete response, 35%) and in 39% of patients with fludarabine-refractory disease (complete response, 3%). Fludarabine, cyclophosphamide, and rituximab induced an overall response in 95% of untreated patients (complete response, 70%)13 and in 73% of patients with relapsed CLL (complete response, 25%).
Oxaliplatin is a third-generation platinum compound in which the platinum atom is complexed with 1,2-diaminocyclohexan carrier ligand and an oxalate ligand.15,16 It has a different spectrum of activity and low cross-resistance with cisplatin17 and a favorable toxicity profile. Oxaliplatin had shown activity in relapsed/refractory NHL. The combination of all these drugs is known as OFAR regimen. It has mostly been explored for Richter’s transformation and refractory CLL that has been previousely treated with fludarabine already.
It is under study: Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter’s Transformation and Leukemias NCT00472849. The goal of this clinical research study is to find the highest tolerable dose of fludarabine and cytarabine that can be given in combination with oxaliplatin and rituximab in the treatment of chronic lymphocytic leukemia (CLL), prolymphocytic leukemia, or Richter’s transformation. Once the highest tolerable dose for this drug combination is found, the next goal of the study will be to find out if this combination therapy is effective in shrinking or slowing the growth of these diseases.
Wierda, W., Tsimberidou, A., O’Brien, S., Ferrajoli, A., Faderl, S., Ravandi, F., Cortes, J., Kantarjian, H., Plunkett, W., Keating, M.
The combination of oxaliplatin, fludarabine (FLU), cytarabine (Ara-c), and rituximab (R) (OFAR) in patients with Richter’s Transformation and FLU-refractory CLL
J Clin Oncol (Meeting Abstracts) 2006 24: 6608
Tsimberidou, Apostolia M., Wierda, William G., Plunkett, William, Kurzrock, Razelle, O’Brien, Susan, Wen, Sijin, Ferrajoli, Alessandra, Ravandi-Kashani, Farhad, Garcia-Manero, Guillermo, Estrov, Zeev, Kipps, Thomas J., Brown, Jennifer R., Fiorentino, Albert, Lerner, Susan, Kantarjian, Hagop M., Keating, Michael J.
Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine, and Rituximab Combination Therapy in Patients With Richter’s Syndrome or Fludarabine-Refractory Chronic Lymphocytic Leukemia J Clin Oncol 2008 26: 196-203
T. J. Kipps Chronic Lymphocytic Leukemia: Advances in Assessing Prognosis and Therapy
ASCO Educational Book, January 1, 2009; 2009(1): 385 – 393.