Pentostatin, Cyclophosphamide, and Rituximab Is an Active, Well-Tolerated Regimen for Patients With Previously Treated Chronic Lymphocytic Leukemia

Lamanna, Nicole; Kalaycio, Matt; Maslak, Peter; Jurcic, Joseph G.; Heaney, Mark L.; Brentjens, Renier J.; Zelenetz, Andrew D.; Horgan, Denise; Gencarelli, Alison; Panageas, Katherine S.; Scheinberg, David A.; Weiss, Mark A.

doi:10.1200/jco.2005.04.3836

Cited by 145 publications

(82 citation statements)

References 26 publications

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“…5,[8][9][10][11][12][28][29][30][31][32] Those studies showed that the combined use of rituximab and FA or DCF, with or without cyclophosphamide, resulted in higher OR and CR rates compared with rituximab or PNA alone. It is noteworthy that rituximab increases the effectiveness of standard chemotherapy regimens used in ILM.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 The results of recent clinical studies confirm these preclinical observations and suggest that, in patients with ILM, rituximab in combination with FA can increase the response rate, including the complete response (CR) rate, compared with FA or rituximab alone and has acceptable toxicity. [8][9][10][11][12] In our preliminary study, we demonstrated that the combination of rituximab and 2-CdA is an effective and well tolerated treatment even for heavily pretreated patients with ILM, and the results appeared to be better than the results produced in patients who were treated previously in our institution with 2-CdA alone. 13 Taking into account the observation that the combination of PNA with cyclophosphamide may be more effective than PNA alone, the combined use of rituximab with FA or 2-CdA and cyclophosphamide is an attractive option.…”

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confidence: 88%

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

Robak

Smolewski

Cebula

et al. 2006

Cancer

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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.

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Section: Discussionmentioning

confidence: 99%

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confidence: 88%

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

Robak

Smolewski

Cebula

et al. 2006

Cancer

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“…61 With this combination there was a 75% ORR and 25% CR rate and 72% of patients received planned treatment at full dose. In another trial, 64 untreated patients with high Rai risk or other high-risk biological features (for example, 17% had unmutated immunoglobulin heavy chain), received pentostatin 2 mg/m 2 on day 1, cyclophosphamide 600 mg/m 2 on day 1 and rituximab 375 mg/m 2 on day 1, every 21 days for 6 cycles.…”

Section: Other Rituximab Combinationsmentioning

confidence: 99%

Changing paradigms in the treatment of chronic lymphocytic leukemia

Foon

Hallek

2009

Leukemia

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“…39,40 In a trial for previously treated patients, cyclophosphamide was given at 600 mg/m 2 on day 1, pentostatin 4 mg/m 2 on day 1, and rituximab at 375 mg/m 2 with each course beginning for course 2. 40 Courses were given every 3 weeks and all patients received G-CSF support. Thirty-two previously treated patients with CLL received this regimen and were assessable for response, 75% responded with CR in 25%.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Current and Investigational Therapies for Patients with CLL

Wierda

2006

Hematology

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Clinical and laboratory investigations are driving the rapid change in treatments for patients with chronic lymphocytic leukemia (CLL). Randomized trials have demonstrated superior activity for fludarabine combined with cyclophosphamide versus single-agent fludarabine or chlorambucil as initial treatment. Chemoimmunotherapy holds promise for further improvement and is being tested in randomized trials. New combinations and agents are being identified and tested. Eliminating minimal residual disease is a therapeutic endpoint that may prove to prolong survival and is also under investigation in prospective clinical trials. Work continues toward improving survival and potentially curing patients of this disease.

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Pentostatin, Cyclophosphamide, and Rituximab Is an Active, Well-Tolerated Regimen for Patients With Previously Treated Chronic Lymphocytic Leukemia

Cited by 145 publications

References 26 publications

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

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

Changing paradigms in the treatment of chronic lymphocytic leukemia

Current and Investigational Therapies for Patients with CLL

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