Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia

• Published in: British journal of haematology Vol. 119; no. 4; pp. 976 - 984
• Main Authors: Bosch, Francesc, Ferrer, Anna, López‐Guillermo, Armando, Giné, Eva, Bellosillo, Beatriz, Villamor, Neus, Colomer, Dolors, Cobo, Francesc, Perales, María, Esteve, Jordi, Altés, Albert, Besalduch, Joan, Ribera, Josep M., Montserrat, Emili
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-12-2002; Blackwell
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cell Survival - drug effects; Chemotherapy; CLL; cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Disease-Free Survival; Female; fludarabine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Male; Medical sciences; Middle Aged; Mitoxantrone - administration & dosage; Mitoxantrone - adverse effects; mito‐xantrone; MRD; Pharmacology. Drug treatments; Recurrence; Survival Rate; Treatment Outcome; Tumor Cells, Cultured; Vidarabine - administration & dosage; Vidarabine - adverse effects; Vidarabine - analogs & derivatives; Antineoplastic agent; Relapse; CLL; Toxicity; Lymphoproliferative syndrome; Evolution; Mitoxantrone; Human; Purine nucleotide; Drug combination; Treatment resistance; Anthraquinone derivatives; Treatment efficiency; Mortality; Minimal residual disease; Malignant hemopathy; mitoxantrone. MRD; Alkylating agent; Chemotherapy; Chronic; Cyclophosphamide; Chronic lymphocytic leukemia; Oxazaphosphinane derivatives; Fludarabine; Treatment; Antimetabolic; Nitrogen mustard
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2002.03959.x

We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and mitoxantrone (FCM) in patients with relapsed or resistant chronic lymphocytic leukaemia (CLL). In total, 37 patients with recurrent or resistant CLL received FCM: fludarabine 25 mg/m2 intravenously (IV), d 1–3; cyclophosphamide 200 mg/m2 IV, d 1–3; and mitoxantrone 6 mg/m2 IV, d 1, at 4‐week intervals for up to six courses. Moreover, 23 patients received FCM with cyclophosphamide 600 mg/m2 i.v. and mitoxantrone 8 mg/m2 i.v. on d 1. In addition to clinical methods, response was assessed using cytofluorometric and molecular techniques. ‘In vitro’ sensitivity to the FCM regimen was also analysed in 20 samples. The median number of courses given was 3 (range: 1–6). Overall, 30 patients (50%) achieved complete response (CR), including 10 cases of negative minimal residual disease (MRD(–)) (17%), and 17 (28%) partial response (PR). The median duration of response was 19 months. ‘In vitro’ sensitivity also correlated with CR achievement (P = 0·04). Main toxicity consisted of neutropenia, infections (8% of courses), and nausea and vomiting. The treatment‐related mortality was 5%. FCM did not hamper stem cell harvesting in patients who were candidates for autologous stem cell transplantation. FCM induced a high CR rate, including an important number of MRD(–), in patients with previously treated CLL.