Fludarabine Plus Epirubicin in Untreated or Minimal Pretreated Patients with Chronic Lymphocytic Leukemia  – Preliminary Results of a Phase-ll Study

Rummel, Mathias; Renner, C.; Josten, K.; Reinhardt, Uwe E.; Rendenbach, B.; Pielken, H.-J.; Wojatschek, C.; Lengfelder, Eva; Mitrou, Paris S.; Hoelzer, Dieter; Bergmann, Lothar

doi:10.1159/000218964

Cited by 3 publications

(2 citation statements)

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“…21 Previous studies revealed that the response rate was not lower when 2-CdA or FAMP were combined with either cyclophosphamide, 14,31-33 mitoxantrone 17,34 or anthracycline. 35 Minimal residual disease (MRD) was evaluated by twocolor immunophenotyping in the patients who fulfilled morphological criteria for CR. MRD was identified in seven out of 18 patients (38.9%).…”

Section: Discussionmentioning

confidence: 99%

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia

et al. 2001

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The objective of the study was to determine the effectiveness and the toxicity of a combined chemotherapy consisting of cladribine (2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of previously untreated B cell chronic lymphocytic leukemia (B-CLL). From August 1998 to December 2000 2-CdA was administered at a dosage of 0.12 mg/kg for 3 (CMC3) or 5 (CMC5) consecutive days, mitoxantrone at 10 mg/m 2 on day 1 and cyclophosphamide at 650 mg/m 2 on day 1 to 62 patients with advanced or progressive B-CLL. The cycles were repeated at 4 week intervals or longer if severe myelosuppression occurred. Twenty patients received CMC5 and 42 patients CMC3. Within the analyzed group an overall response (OR) rate (CR+PR) of 64.5% (95% CI: 52.7-76.3%) was reported, including 29.0% CR. There was no difference in the CR rate between the patients treated with CMC5 (30%) and CMC3 (28.6%) (P = 0.9), nor in the OR rate (55.0% and 69.0%, respectively, P = 0.3). Residual disease was identified in seven out of 18 (38.9%) patients who were in CR, including two treated with CMC5 and five treated with CMC3 protocols. CMC-induced grade III or IV thrombocytopenia occurred in 12 (19.4%) of patients, including four (20%) CMC5-treated and eight (19%) CMC3-treated patients (P = 0.8). Neutropenia grade III or IV was observed in seven (35%) and 11 (26.2%) patients, respectively (P = 0.8). Severe infections, including pneumonia and sepsis, occurred more frequently after CMC5 (11 patients, 55.0%) than CMC3 (10 patients, 28.6%) (P = 0.03) Fourteen patients died, including six treated with CMC5 and eight treated with CMC3 (30% and 19%, respectively). Infections were the cause of death in nine patients, including four in the CMC5 group and five in the CMC3 group. In conclusion, our results indicate that the CMC programme is an active combined regimen in previously untreated B-CLL patients; its efficiency seems to be similar to that observed earlier in B-CLL patients treated with 2-CdA as a single agent. However, toxicity, especially after CMC5 administration, is significant. Therefore, we recommend the CMC3 but not the CMC5 programme for further evaluation. Leukemia (2001Leukemia ( ) 15, 1510Leukemia ( -1516

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Section: Discussionmentioning

confidence: 99%

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia

et al. 2001

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“…However, the efficacy and toxicity of these combinations should be carefully evaluated in prospective randomized trials. 214,307,310 (74) 88 (35) 69 (10) 65 (9) Weiss et al …”

Section: Combinations Of Purine Analogues and Other Drugsmentioning

confidence: 99%

B‐chronic lymphocytic leukemia: practical aspects

Pangalis

Vassilakopoulos

Dimopoulou

et al. 2002

Hematological Oncology

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B-CLL is the most common adult leukemia in the Western world. It is a neoplasia of mature looking B-monoclonal lymphocytes co-expressing the CD5 antigen (involving the blood, the bone marrow, the lymph nodes and related organs). Much new information about the nature of the neoplastic cells, including chromosomal and molecular changes as well as mechanisms participating in the survival of the leukemic clone have been published recently, in an attempt to elucidate the biology of the disease and identify prognostic subgroups. For the time being, clinical stage based on Rai and Binet staging systems remains the strongest predictor of prognosis and patients' survival, and therefore it affects treatment decisions. In the early stages treatment may be delayed until progression. When treatment is necessary according to well-established criteria, there are nowadays many different options. Chlorambucil has been the standard regimen for many years. During the last decade novel modalities have been tried with the emphasis on fludarabine and 2-chlorodeoxyadenosine and their combinations with other drugs. Such an approach offers greater probability of a durable complete remission but no effect on overall survival has been clearly proven so far. Other modalities, included in the therapeutic armamentarium, are monoclonal antibodies, stem cell transplantation (autologous or allogeneic) and new experimental drugs. Supportive care is an important part of patient management and it involves restoring hypogammaglobulinemia and disease-related anemia by polyvalent immunoglobulin administration and erythropoietin respectively.

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Phase II Study of 2-Chlorodeoxyadenosine in Combination With Chlorambucil in Previously Untreated B-Cell Chronic Lymphocytic Leukemia

Tefferi

Levitt

et al. 1999

American Journal of Clinical Oncology: Cancer Clinical Trials

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The objective was to determine the safety and efficacy of adding a maximally tolerated dose of 2-chlorodeoxyadenosine (2-CdA) to standard chlorambucil (CLB) therapy in previously untreated B-cell chronic lymphocytic leukemia (CLL). Thirty patients with CLL (median age, 64 years) received two courses of 2-CdA given intravenously (2 mg/m2 daily for 7 days) added to biweekly administration of CLB at 30 mg/m2 given orally. The diagnosis of CLL, treatment indications, and response criteria were according to the National Cancer Institute established guidelines. Sixteen patients (53%) had advanced-stage disease, and four (13%) had trisomy 12 abnormality. The overall remission rate was 80%, including 20% complete remission (CR), 30% nodular partial remission (nPR), and 30% partial remission (PR). Minimal residual disease was detected phenotypically in two of five patients with CR and in eight of nine with nPR. Overall, CR, nPR, and PR rates were not influenced significantly by the presence of cytogenetic abnormalities or advanced clinical stage. With a median follow-up of 33 months, 58% of patients who had a response had relapse. Median time to progression in all 30 patients was 30 months, and time to progression and progression-free survival were not significantly different for the different response groups, clinical stages, or cytogenetic groups. Severe neutropenia and thrombocytopenia occurred in 33% and 7% of patients, respectively. Only two patients had documented bacterial infections, and four had herpetic infections. Concurrent combination chemotherapy with abbreviated doses of 2-CdA and standard-dose CLB is feasible and safe in previously untreated CLL. Antitumor activity may be superior to that of CLB alone given in conventional doses. Whether a different schedule of combining these two agents would result in improved outcome is being investigated.

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Fludarabine Plus Epirubicin in Untreated or Minimal Pretreated Patients with Chronic Lymphocytic Leukemia – Preliminary Results of a Phase-ll Study

Cited by 3 publications

References 8 publications

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia

B‐chronic lymphocytic leukemia: practical aspects

Phase II Study of 2-Chlorodeoxyadenosine in Combination With Chlorambucil in Previously Untreated B-Cell Chronic Lymphocytic Leukemia

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