Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: a report from the non-Hodgkin's lymphoma co-operative study group.

Abstract

The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL), Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36-70), received FLU/CY/MITO regimen (FLU 25 mg/m2 days 1-3, CY 300 mg/m2 days 1-3, Mito 10 mg/m2 day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87%: 46 patients achieved complete response (CR) (77%), 6 a partial response (10%) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2% and 45% respectively. Thirty-five patients (58%) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76%) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.

• Authors: Gino Santini, Teodoro Chisesi, Sandro Nati, Adolfo Porcellini, Valerio Zoli, Vittorio Rizzoli, Simona Zupo, Gennaro Marino, Alessandra Rubagotti, Alessandro Polacco, Mauro Spriano, Renato Vimercati, Angela Marina Congiu, Jean Louis Ravetti, Savina Aversa, Marco Candela, Caterina Patti
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 45 Issue 6 Pg. 1141-7 (Jun 2004) ISSN: 1042-8194 [Print] United States
• PMID: 15359993 (Publication Type: Journal Article)

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• Cyclophosphamide
• Mitoxantrone
• Vidarabine
• fludarabine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bone Marrow
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Female
• Humans
• Lymphoma, Follicular (drug therapy, mortality)
• Male
• Middle Aged
• Mitoxantrone (administration & dosage)
• Neoplasm, Residual (drug therapy)
• Protein Transport
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Safety
• Survival Rate
• Treatment Outcome
• Vidarabine (administration & dosage, analogs & derivatives)