Phase II trial of 4′-epi-doxorubicin in metastatic colorectal carcinoma

Wils, J.

doi:10.1007/bf00171592

Cited by 8 publications

(1 citation statement)

References 5 publications

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“…Topoisomerase‐2A (Top2A) is the cellular target of anthracyclines and two meta‐analyses recently confirmed that breast cancer patients with increased TOP2A gene copy number had increased benefit from adjuvant anthracycline treatment (Di Leo et al., 2011), (Du et al., 2011). A number of small and non‐randomized clinical studies have suggested a 10–20% objective response rate following anthracycline treatment of mCRC (Michaelson et al., 1982), (Wils, 1984) and we have now initiated a prospective phase II clinical trial in which metastatic CRC patients with TOP2A gene amplification in their cancer cells are offered treatment with the Top2 inhibitor epirubicin (EudraCTno. 2013‐001648‐79).…”

Section: Introductionmentioning

confidence: 99%

Topoisomerase‐1 and ‐2A gene copy numbers are elevated in mismatch repair‐proficient colorectal cancers

et al. 2015

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Our results show that TOP1 and TOP2A gene copy numbers are increased in the pMMR subgroup. We propose that this preference may reflect a selective pressure to gain and/or maintain the gained extra copies of topoisomerase genes whose products are required to cope with high replication stress present in the pMMR tumors, thereby providing a survival advantage selectively in pMMR tumors. Future studies should test this concept and explore potential differences between pMMR and dMMR tumors in response to Top1 and Top2 inhibitors.

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Section: Introductionmentioning

confidence: 99%

Topoisomerase‐1 and ‐2A gene copy numbers are elevated in mismatch repair‐proficient colorectal cancers

et al. 2015

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Phase I and II Agents in Cancer Therapy: I. Anthracyclines and Related Compounds

Wadler

Fuks

Wiernik

1986

The Journal of Clinical Pharma

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Anthracycline antibiotics remain among the most potent anticancer drugs, but their efficacy is limited by the development of a dose-dependent irreversible cardiomyopathy and by the emergence of clones of tumor cells resistant to the effects of the drug. Modifications of the basic anthracycline structure have resulted in molecules that may share the activity of the parent compound, with amelioration of some toxicities, absence of cross-resistance, or activity against tumors insensitive to the parent drug. Epirubicin has a unique metabolic pathway, glucuronidation, that may result in more rapid plasma clearance and reduced toxicity as compared with doxorubicin. Epirubicin has demonstrated comparable activity to doxorubicin in breast cancer, with possibly reduced toxicity. Idarubicin is of interest because of its cytotoxic activity when given orally. Idarubicin has prolonged retention in the plasma and has equal cytotoxic activity to the parent compound. Idarubicin has demonstrated activity against acute leukemia and breast cancer; in the latter tumor category, some doxorubicin-resistant tumors have responded. Esorubicin is of interest because of its nearly absent cardiac toxicity. This agent has some activity against solid tumors and is currently being clinically tested. Aclacinomycin A is an anthracycline in which a trisaccharide is substituted for the aminosugar. Aclacinomycin A and the related compound marcellomycin are of interest as both cytotoxic and differentiating agents. Menogaril is an anthracycline with the aminosugar on the D ring; it does not exhibit cross-resistance with doxorubicin or cardiotoxicity. Mitoxantrone is a compound that is related to the anthracyclines but has a different mechanism of action. This agent has significant activity against acute leukemia and breast cancer and is currently being compared with doxorubicin. Amsacrine is another compound related to the anthracyclines that possesses major activity against acute leukemias. Minor modifications of the anthracycline molecule have had major impact on the biologic activity of these drugs. New anthracycline analogues with up to 100 times the potency of currently available anthracyclines are being developed for clinical testing, and these complex molecules retain a nearly unlimited potential for structural modification.

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