amrubicin and Anemia

Therapeutic drug monitoring (TDM) is widely applied to a variety of medications, including antibiotics, immunosuppressants, and antidepressants, but the clinical utility of TDM for anticancer agents is currently limited by several factors. The primary reason is the poorly-defined concentration-effect relationships for most anticancer drugs. TDM has the potential to improve the clinical use of anticancer agents. This paper reviews the relations between the pharmacokinetics of a new anticancer agent, amrubicin, and the clinical response and toxic side effects in patients. The plasma concentration of amrubicin peaked immediately after a bolus intravenous injection of the drug and declined in a biexponential manner thereafter, whereas that of C-13 hydroxy metabolite amrubicinol also peaked just after amrubicin injection but decreased more gradually compared with that of amrubicin. The apparent total clearance of amrubicin showed a large interindividual variability, despite adjustment of dosage for body surface area. Leukocytopenia of grades 3 or 4 occurred in most patients, and thrombocytopenia and anemia of grades 3 or 4 were also common. Since the area-under the curves of amrubicin and amrubicinol seemed to be associated with the severity of hematological toxicities, it is thought that the plasma concentration of amrubicin and amrubicinol may provide useful information for establishing the optimal dosage of amrubicin in each patient.

Topics: Aged; Anemia; Anthracyclines; Antineoplastic Agents; Body Surface Area; Drug Monitoring; Humans; Leukopenia; Male; Metabolic Clearance Rate; Middle Aged; Thrombocytopenia

We conducted a multicenter phase II study of amrubicin, a novel 9-aminoanthracycline, to evaluate its efficacy and safety in patients with non-small-cell lung cancer (NSCLC).. Entry requirements included cytologically or histologically proven measurable NSCLC, stage III or IV, no prior therapy, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and adequate organ function. Amrubicin was given by daily intravenous injection at 45 mg/m2/day for three consecutive days, repeated at 3 week intervals. Each patient received at least three treatment cycles.. Sixty-two patients were enrolled in this study. Of the 62 registered patients, 60 were eligible and assessable for efficacy, and 59 for toxicity. Overall response rate was 18.3% (95% confidence interval [CI], 9.5 to 30.4%) and median survival time was 8.2 months (95% CI, 6.7 to 10.4 months). Major toxicity was myelosuppression, with incidences of grade 3 or 4 toxicity of 78.0% for neutropenia, 54.2% for leukopenia, 30.5% for anemia, and 28.8% for thrombocytopenia. Non-hematological toxicities with a greater than 50% incidence were anorexia (69.5%), nausea/vomiting (55.9%), and alopecia (75.9%), but were relatively mild, with grade 3 toxicities observed in only one patient each (1.7%).. Amrubicin was an active, well-tolerated agent in the treatment of NSCLC.

Topics: Adult; Aged; Anemia; Anthracyclines; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Female; Humans; Japan; Leukopenia; Lung Neoplasms; Male; Middle Aged; Survival Analysis

We retrospectively investigated amrubicin hydrochloride(AMR)monotherapy as second or thirdline chemotherapy for small-cell lung cancer(SCLC)and assessed its efficacy and safety. AMR was intravenously administered at 25-45mg/m2 for 3 consecutive days every 3-4 weeks. Fifty-three patients were enrolled. Response rates and median survival times were as follows: total cases, 32% and 7. 4 months; sensitive relapse cases, 64% and 16. 4 months; refractory relapse cases, 27% and 5. 9 months. Neutropenia was major toxicity(Grade 3 or 4 was observed in 72% of the subjects), whereas nonhematologic toxicities were mild. Treatment with AMR appeared effective in SCLC patients previously treated with chemotherapy. On the other hand, it must be used carefully because of its relatively severe hematologic toxicities.

Topics: Aged; Aged, 80 and over; Anemia; Anthracyclines; Antineoplastic Agents; Female; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Recurrence; Retrospective Studies; Salvage Therapy; Small Cell Lung Carcinoma; Thrombocytopenia; Treatment Outcome

Our previous study showed that the myelosuppression induced by a single-bolus intravenous injection of amrubicin into mice was more severe, even at half the maximum tolerated dose (MTD), than that induced by adriamycin (ADR) at the MTD, but that the recovery was more rapid than that after ADR. The present study shows that the administration of amrubicin significantly decreased the number of colony-forming units of granulocytes and monocytes (CFU-GM) from day 1, but that the CFU-GM numbers recovered by day 3. In contrast, the administration of ADR induced a continuous decrease in the numbers of CFU-GM until day 10. The early myelosuppression and rapid recovery of white blood cells (WBC) induced by amrubicin may depend upon the early decrease in the number of CFU-GM and the rapid recovery of CFU-GM. These data suggest that the toxic effects on the peripheral blood and bone marrow induced by amrubicin are more reversible and more controllable than those induced by ADR.

Topics: Anemia; Animals; Anthracyclines; Antineoplastic Agents; Blood Platelets; Bone Marrow; Colony-Forming Units Assay; Doxorubicin; Erythrocytes; Granulocytes; Hematocrit; Hematopoietic Stem Cells; Hemoglobins; Leukopenia; Mice; Mice, Inbred ICR; Monocytes