Doxorubicin prostate cancer

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

S. R. Khan, S. R. Denmeade, In vivo Activity of a PSA-Activated Doxorubicin Prodrug against PSA-Producing Human Prostate Cancer Xenografts , Prostate 2000, 45, 80-83. 

In September 2007, the EMEA approved the use of trabectidin against ovarian cancer (OC) and STS. In November 2009, Yondelis received its second marketing authorization from the European Commission for its administration in combination with pegylated liposomal doxorubicin (Doxil, Caelyx) for the treatment of women with relapsed ovarian cancer presently, trabectedin (36) is under Phase II trials for the treatment of paediatric sarcomas as well as breast and prostate cancers. The European Commission and the US Food and Drug Administration (FDA) have granted orphan drug status to trabectedin for soft tissue sarcomas and... 

Figure 3.1 Combined effects of a combination of 7 anticancer drugs with different sites of action. Shown are the predicted (solid line concentration addition, broken line independent action), and the observed (circles) cytotoxic effects on DU 145 prostate cancer cells. Doxorubicin, daunorubicin, vincristin, cis-platin, etoposide, melphalan and 5-fluorouracil were combined at equitoxic concentrations. The mixture effect predictions were derived from the concentration-response curves of the individual anticancer drugs...

Tetrapeptide quinones derived from (3-lapachone, (II), and doxorubicin, (III), prepared by Blokhin (4) were effective against human lung adenocarcinoma cell line, A549, and human prostatic cancer cell line, DUPRO. 

Doxorubicin combined Prostate cancer Pharmacia III, Neopharm III... 

Neville-Webbe, H.L., Rostami-Hodjegan, A., Evans, C.A., Coleman, R.E., and Holen, I. (2005). Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer 113 364-371. 

A flare phenomenon is a well-documented effect of hormonal therapies and/or hormone-responsive tumors. A prostate-specific antigen flare occurred in four of 28 patients who received liposomal doxorubicin (Caelyx) for symptomatic androgen-independent prostate cancer (40). 

Tu SM, Pagliaro LC, Banks ME, Amato RJ, Millikan RE, Bugazia NA, Madden T, Newman RA, Logothetis CJ. Phase I study of suramin combined with doxorubicin in the treatment of androgen-independent prostate cancer. Clin Cancer Res 1998 4(5) 1193-201. 

Docetaxel and prednisone have recently been shown to improve survival in hormone-refractory metastatic prostate cancer and should be considered standard therapy. Single agents with modest activity in prostate cancer include cyclophosphamide, estramustine, 5-fluorouracil, methotrexate, dacarbazine, mitoxantrone, doxorubicin, pachtaxel, gemcitabine, vinorelbine, and cisplatin. If disease stabilization is included as a favorable response, response rates np to 46% have been reported. Several trials have evalnated the varions combination regimens containing the most active single agents. ... 

Jayaprakash S, Wang X, Heston WD, Kozikowski AP. Design and synthesis of a PSMA inhibitor-doxorubicin conjugate for targeted prostate cancer therapy. Chem Med Chem. 2006 1 299. 

Erederiksen, L.J., Siemens, D.R., Heaton, J.R, Maxwell, L.R., Adams, M.A., and Graham, C.H. (2003). Hypoxia induced resistance to doxorubicin in prostate cancer cells is inhibited by low concentrations of glyceryl trinitrate. J. Urol. 170, 1003-1007. 

It has been known for some time that doxorubicin (DOX) can inhibit the production of NO in colorectal cancer cells, in a manner that is dependent on iNOS transcription (Jung et al. 2002) and that the inhibition of NOS (by the non-isoform-specific L-NMMA) can lead to a dramatic increase in the resistance of breast cancer cells (MDA-MB-231) to DOX in a manner that was similar to hypoxia-induced DOX resistance (Matthews et al. 2001). Addition of the NO donors DETA/NO or GTN partially reversed the hypoxia-induced resistance to DOX. Very similar data were also obtained in DU-145 prostate cancer cells (Frederiksen et al. 2003). In vitro, hypoxia caused resistance to DOX, but that could be partially reversed by exposure of the cells to even low concentrations of the NO donors GTN or isosorbide dinitrate. The chemosensitising effect of GTN, administered via a transdermal patch, was also demonstrated in PC3 xenografts in nude mice (Frederiksen et al. 2007). DOX (4 mg/kg biweekly, i.p.) alone had litde effect on tumour growth, but there... 

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