Rituximab combined with cladribine or with cladribine and cyclophosphamide in heavily pretreated patients with indolent lymphoproliferative disorders and mantle cell lymphoma

Abstract

BACKGROUNDIn vitro studies have shown synergistic or additive interactions between rituximab and purine nucleoside analogues. The results of recent clinical trials seem to confirm these preclinical observations.METHODSFor the current study, the authors evaluated the feasibility, efficacy, and toxicity of combined regimens that consisted of either rituximab plus cladribine (2‐CdA) (the RC regimen) or RC plus cyclophosphamide (the RCC regimen) in the treatment of patients with heavily pretreated, indolent lymphoid malignancies. Fifty‐four adult patients with recurrent or refractory, low‐grade non‐Hodgkin lymphoma (LG‐NHL) and B‐cell chronic lymphocytic leukemia (B‐CLL) were treated according to the RC/RCC regimens. The RC protocol consisted of intravenous rituximab at a dose of 375 mg/m2 on Day 1 and 2‐CdA at a dose of .12 mg/kg per day on Days 2 through 6. The RCC protocol consisted of rituximab at a dose of 375 mg/m2 on Day 1, 2‐CdA at a dose of 0.12 mg/m2 on Days 2 through 4, and intravenous cyclophosphamide at a dose of 250 mg/m2 per day on Days 2 to 4. The RC/RCC courses were repeated at 4‐week intervals.RESULTSThirty‐three patients with B‐CLL, 12 patients with LG‐NHL and 9 patients with mantle cell lymphoma (MCL) entered the study. Thirty‐three patients (61%) had recurrent disease after prior therapy, and 21 patients (39%) had refractory disease. Thirty‐one patients were treated on the RC regimen, and 23 patients were treated on the RCC regimen. Six patients (11%) achieved a complete response, and 33 patients (60%) achieved a partial response. The median failure‐free survival of responders was 10.5 months. The treatment revealed tolerability, with episodes of severe neutropenia (Grade 3 and 4 [according to World Health Organization criteria]) observed in 6 patients (11%), episodes of Grade 3 and 4 infections observed in 11 patients (20%), and episodes of Grade 3‐4 thrombocytopenia observed in 4 patients (7%).CONCLUSIONSThe RC and RCC regimens were highly effective and well tolerated modalities of treatment in heavily pretreated patients with indolent lymphoproliferative disorders. Cancer 2006. © 2006 American Cancer Society.

Efficacy and safety of front-line therapy with fludarabine-cyclophosphamide-rituximab regimen for chronic lymphocytic leukemia outside clinical trials: the Israeli CLL Study Group experience

“…In an attempt to reduce associated toxicity, some investigators used modified FCR-based regimens, employing protocols with reduced doses of chemotherapy and increased amounts of rituximab, 12 sequential F→C→R regimen, 13 and even substitution of fludarabine by pentostatin 14 or cladribine. 15,16 The present study aimed to evaluate the efficacy and safety of the FCR regimen for physically fit This study aimed to evaluate the efficacy and safety of the fludarabine-cyclophosphamide-rituximab regimen for young physically fit patients with chronic lymphocytic leukemia in the "real-life" setting. We specifically focused on the impact of dose reduction on patient outcomes.…”

Beyond hairy cell: the activity of cladribine in other hematologic malignancies

“…41 Among a different group of 9 MCL patients given cladribine in combination with cyclophosphamide and rituximab, 6 patients responded with 2 obtaining a CR. 43 These results demonstrate that cladribine is highly active both as a single agent and as a component of combination therapy for MCL patients. Single-agent use of cladribine may be appropriate in selected patient populations, but the incorporation of cladribine into future multiagent approaches will probably be most effective.…”

“…Studies evaluating cladribine in combination with cyclophosphamide, mitoxantrone, or rituximab reported superior response rates compared with single-agent cladribine (Table 2). [37][38][39][40][41][42][43][44][45] However, as is often the case in studies with indolent lymphomas, there were no statistical differences in overall survival (OS). Toxicities were typically hematologic and infectious, and were generally not severe.…”

Randomized comparison of cladribine alone or in combination with cyclophosphamide, and cyclophosphamide, vincristine and prednisone in previously untreated low‐grade B‐cell non‐Hodgkin lymphoma patients

“…26 In addition, high activity of cladribine alone or cladribine and cyclophosphamide combination and rituximab has also been observed. 27,28 Although purine analogs are generally well tolerated, and their toxicity profile seems comparable to other regimens, both fludarabine and cladribine are associated with immunosuppression, and physicians should be aware of an increased risk of opportunistic infections. 27 The therapeutic strategy adopted in this study was aimed at minimizing the potential for cumulative myelosuppression and immunosuppression.…”