Disease relevance of Amrubicin

• This multicenter phase II study was conducted to evaluate the efficacy and safety of amrubicin in patients with non-small-cell lung cancer (NSCLC) [1].
• CONCLUSION: Amrubicin exerted promising antitumor activity on NSCLC with acceptable toxicity [2].
• BACKGROUND: Amrubicin, a totally synthetic 9-amino-anthracycline, demonstrated excellent single-agent activity for extensive-stage small-cell lung cancer (ED-SCLC) [3].
• In addition, three patients who had had asymptomatic interstitial pneumonitis, identified by diagnostic imaging before treatment, aggravated after amrubicin treatment; two of them died [1].
• The Cmax and AUC of amrubicin were correlated with the duration of grade 4 neutropenia [4].

High impact information on Amrubicin

• The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 as well as the dose-limiting toxicities (DLT) of this combination in patients with advanced non-small cell lung cancer [5].
• Amrubicin did not affect the pharmacokinetics of CPT-11, SN-38 or SN-38 glucuronide [5].
• CONCLUSION: The combination of amrubicin and CPT-11 seems to be active against non-small cell lung cancer with acceptable toxicity [5].
• The maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) of amrubicin increased in a dose-dependent manner [4].
• Amrubicinol attained similar intracellular concentrations at lower medium concentrations compared to amrubicin, and the intracellular concentration of amrubicinol necessary to produce 50% cell growth inhibition was 3 to 8 times lower than that of amrubicin in 4 cell lines tested [6].

Chemical compound and disease context of Amrubicin

• In phase II trials, amrubicin has shown activity equivalent to that of doxorubicin on non-Hodgkin's lymphoma, response rates exceeding 20% on non-small-cell lung cancer, and a response rate of 78.8% on untreated extensive-stage small-cell lung cancer [7].
• Additive effects of amrubicin with cisplatin on human lung cancer cell lines [8].

Biological context of Amrubicin

• The purpose of this study was to characterize the pharmacokinetics of amrubicin and its active metabolite amrubicinol [9].
• The starting dose of amrubicin was 25 mg/m(2), and it was escalated in 5 mg/m(2) increments until the maximum tolerated dose was reached [5].
• A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex [10].
• The tissue distribution of a novel antitumor anthracycline antibiotic, amrubicin, was studied using seven human tumor xenografts implanted into nude mice, in order to identify the principal factors determining its therapeutic efficacy [11].
• DOX-induced apoptosis was mainly initiated by oxidative DNA damage in comparison with the ability of other topoisomerase inhibitors (TAS-103, amrubicin and amrubicinol) to cause DNA cleavage and apoptosis [12].

Anatomical context of Amrubicin

• High metabolic activity of amrubicin to amrubicinol was detected in tumor tissue homogenates, especially in cell lines highly sensitive to amrubicin in vivo [11].
• In this study, the in vitro activities of amrubicin and its major metabolite, amrubicinol, were examined using 17 human tumor cell lines [6].
• This did not change the rates of amrubicin and amrubicinol metabolism in either human liver microsomes or cytosol [13].
• Hvrl00-6 cells showed 2- to 200-fold higher resistance to anthracyclines than HeLa cells, and unexpectedly showed slight resistance to idarubicin and amrubicin [14].
• 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 [15].

Associations of Amrubicin with other chemical compounds

• The cytotoxic effects of 27 anticancer drugs including amrubicin, vinorelbine, paclitaxel, docetaxel, gemcitabine, and irinotecan were evaluated in human cervical carcinoma HeLa cells, and drug-resistant HeLa-derived Hvrl-1, HvrlO-6, and Hvr100-6 cells, which were newly established by stepwise exposure to vinblastine [14].
• 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 [15].

Gene context of Amrubicin

• Amrubicin and its C-13 alcohol metabolite, amrubicinol, inhibited purified human DNA topoisomerase II (topo II) [10].
• The single agent of amrubicin is active in untreated small-cell lung cancer (SCLC) [16].
• The results indicate that metabolism of amrubicin is mediated by NADPH-cytochrome P450 reductase, NADPH:quinone oxidoreductase and carbonyl reductase [13].

Analytical, diagnostic and therapeutic context of Amrubicin

• Amrubicin was administered by daily intravenous injection at 45 mg/m2/day for 3 consecutive days every 3 weeks [1].
• It has been reported that the 9-aminoanthracycline amrubicin shows good efficacy in human tumor xenograft models [17].
• The pharmacokinetics analysis of amrubicin and amrubicinol was performed by high-performance liquid chromatography [9].
• The recommended phase II dose of amrubicin for patients with lung cancer refractory to standard chemotherapy is thus 35 mg/m(2) once a day for three consecutive days every 3 weeks [18].
• PATIENTS AND METHODS: Eleven patients with stage IIIB or IV disease were treated at 3-week intervals with amrubicin (5-min intravenous injection on days 1-3) plus 60 mg/m(2) of CPT-11 (90-min intravenous infusion on days 1 and 8) [5].

References