aclarubicin and Neutropenia

One hundred twelve patients with geriatric acute myeloid leukemia (AML), refractory or relapsed AML, or myelodysplastic syndrome and refractory anemia with excess of blasts in transformation (MDS-RAEBt) were entered into this study to receive CAG (aclarubicin and low-dose cytosine arabinoside [Ara-C]in combination with granulocyte colony-stimulating factor [G-CSF]) with the objective of evaluating the efficacy and tolerance of this regimen. Low-dose Ara-C was given subcutaneously at a dosage of 10 mg/m2 every 12 hours on days 1 to 14. Aclarubicin was administered intravenously at a dosage of 14 mg/m2 per day on days 1 to 4 (CAG regimen A) or 7 mg/m2 on days 1 to 8 (CAG regimen B). Recombinant G-CSF was given subcutaneously at a dosage of 200 3g/m2 per day on days 1 to 14. We demonstrated comparable overall complete remission rates for the 4 groups of patients: 30.8% (8/26) in the elderly patients, 48.4% (30/62) in the refractory AML patients, 44.4% (8/18) in the relapsed AML patients, and 38.5% (5/13) in the MDS-RAEBt patients. Of the 52 patients followed up, the 12-month progression-free survival (PFS) and overall survival (OS) rates estimated by the Kaplan-Meier method were 40.73% 3 8.15% and 42.85% 3 8.23%, respectively. The median PFS and OS times were 9.0 3 2.2 months and 11.0 3 1.6 months, respectively. Toxic effects were very rare and mainly consisted of neutropenia and thrombocytopenia due to myelosuppression; approximately 70% to 80% of patients had neutropenia or thrombocytopenia that exceeded National Cancer Institute grade II. Nonhematologic toxicities were not observed in this study. The CAG regimen seems promising, with acceptable toxicity, for the treatment of various categories of poor-prognosis AML and MDS-RAEBt.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Dose-Response Relationship, Drug; Female; Granulocyte Colony-Stimulating Factor; Humans; Injections, Subcutaneous; Leukemia, Myeloid; Male; Middle Aged; Myelodysplastic Syndromes; Neutropenia; Survival Analysis; Thrombocytopenia; Treatment Outcome

In order to develop new strategies for the treatment of relapsed or refractory acute myeloid leukemia, the German AML Cooperative Group performed a prospective multicenter phase II study to evaluate the antileukemic efficacy of aclarubicin 60 mg/m2/day and etoposide 100 mg/m2/day each given for 5 days. Of 37 heavily pretreated evaluable patients (median age 42 years, range 18-81) 15 (40%) achieved a remission after one or two courses of treatment consisting of nine complete (24%) and six partial remissions (16%). Fourteen (38%) cases were non-responders and eight (22%) patients suffered from early deaths. Disease-free survival for patients in remission and overall survival were 3.2 months each. The median duration of critical neutropenia <500/microl was 27 days. The most frequent non-hematologic side-effects were stomatitis (WHO III/IV, 48%), infections (40%), nausea/vomiting (26%) and diarrhea (24%). Cardiac toxicity was mild. This study suggests a substantial antileukemic efficacy and an acceptable toxicity of aclarubicin in combination with etoposide in heavily pretreated patients with advanced acute myeloid leukemia, and warrants further evaluations in a more favorable stage of the disease.

Topics: Aclarubicin; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Etoposide; Female; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Middle Aged; Neutropenia; Prospective Studies; Recurrence; Stomatitis; Survival Rate

Topics: Aclarubicin; Adenocarcinoma; Adult; Aged; Alopecia; Antibiotics, Antineoplastic; Breast Neoplasms; Drug Evaluation; Female; Humans; Middle Aged; Naphthacenes; Nausea; Neoplasm Metastasis; Neutropenia

Acute myeloid leukaemia (AML) with t (8;21) or inv (16), called core binding factor (CBF) AML, has a favourable prognosis. However, some CBF-AML patients have persistent measurable residual disease (MRD) and are more likely to relapse after standard chemotherapy treatment. The CAG regimen, composed of cytarabine, aclarubicin and granulocyte colony-stimulating factor, has been proven to be effective and safe in treating refractory AML patients. We performed a retrospective study to evaluate the efficacy of the CAG regimen to eliminate MRD detected by RUNX1::RUNX1T1 and CBFβ::MYH11 transcript levels by quantitative polymerase chain reaction (Q-PCR) among 23 patients. Molecular response was defined as the ratio of fusion transcript after treatment to that before treatment less than or equal to 0.5. The molecular response rate and median decrease ratio of fusion transcripts at the molecular level of the CAG regimen were 52% and 0.53, respectively. The median fusion transcripts before CAG treatment was 0.25% whereas after CAG was 0.11%. Among the 15 patients who had a poor molecular response to the high/intermediate-dose cytarabine regimen, the median decrease ratios of transcripts at the molecular level of high/intermediate-dose cytarabine and CAG were 1.55 and 0.53 (P = 0.028), respectively, and 6 of 15 patients achieved a molecular response to CAG (40%). The median disease-free survival was 18 months, and the overall survival rate at 3 years among all patients was 72.7% ± 10.7%. The common grades 3-4 adverse events were nausea (100%), thrombocytopenia (39%) and neutropenia (37.5%). The CAG regimen may have activity in CBF-AML patients and could provide a new option for patients who have a poor molecular response to high/intermediate-dose cytarabine.

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Core Binding Factors; Cytarabine; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Neoplasm Recurrence, Local; Neutropenia; Retrospective Studies; Treatment Outcome

Thirty-two patients with measurable metastatic colorectal cancer refractory to 5-fluorouracil-containing regimens received aclacinomycin A (ACM-A) on a single-dose I.V. schedule administered over 4 hours every 3 weeks. Good-risk patients received ACM-A at the starting daily dose of 100 mg/m2 while patients who had had therapy with radiation or myelosuppressive drugs such as mitomycin C or a nitrosourea compound received an initial daily dose of 80 mg/m2. There were no complete or partial remissions in this study. Twelve of 30 evaluable patients had disease stabilization. Nausea and vomiting were the dose-limiting toxic effects; myelosuppression was moderate, with neutropenia more severe than thrombocytopenia. Other toxic effects included diarrhea (in 53% of the treatment courses), phlebitis (36%), and mucositis (27%). Alopecia was rare and occurred in 3% of treatment courses, while none of the patients developed clinical manifestation of cardiac toxicity. Aclacinomycin-A administered by the single-dose schedule as used in this study is not effective against colorectal cancer.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Colonic Neoplasms; Drug Evaluation; Female; Humans; Male; Middle Aged; Naphthacenes; Nausea; Neoplasm Metastasis; Neutropenia; Rectal Neoplasms; Thrombocytopenia

Aclacinomycin A (ACM) is a new anthracycline antibiotic that produces substantially less cardiotoxicity in animals than does doxorubicin. To define the effective dose for the treatment of patients with leukemia, we treated 43 patients with acute nonlymphoblastic leukemia (ANLL) or acute lymphoblastic leukemia (ALL) using ACM administered at three dose levels. All patients had previously received extensive treatment with other chemotherapy; their median cumulative dose of prior anthracycline was 340 mg/m2. An ACM dose of 100 mg/m2/day given for 2 days (total dose, 200 mg/m2) failed to produce significant bone marrow hypocellularity or remission in two patients. Total ACM doses of 300--360 mg/m2 (100 or 120 mg/m2/day x 3 days) produced marrow hypoplasia in 16 to 23 evaluable patients with ANLL. Overall, four of 32 patients with ANLL who received 300--360 mg/m2 of ACM achieved complete remission for duration of 1, 5+, 6 and 15+ months. Two of nine patients with ALL achieved partial remission. Toxic effects of this therapy included severe leukopenia and thrombocytopenia, nausea, mucositis, and diarrhea. ECG abnormalities were noted in 43% of patients who were carefully monitored; however, only one patient developed a significant decrease in left ventricular ejection fraction as measured by radionuclide cardiography. ACM produced only minimal alopecia and did not cause tissue necrosis following inadvertent subcutaneous infiltration. We conclude that 300--360 mg/m2 of ACM is an effective dose for the treatment of patients with ANLL and that further evaluation of this compound is indicated in patients who have received minimal prior therapy.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Heart Diseases; Humans; Leukemia; Leukemia, Lymphoid; Middle Aged; Naphthacenes; Neutropenia; Thrombocytopenia