Fwd: The autumn crocus (colchicine) - a new oldboy on the street

[Guest guest]

FYISounds a whole lot better than the current fare. Only docetaxel is licensed for use with castration resistant prostate cancer (CRPC) and sadly, only 50% of men are responders to this drug after a course of treatment. [ See foot of this email PMID21844499]. The new drug looks like it works 50% of the time after one dose, so hopefully after half a dozen doses the cancer will be cleared. The new drug is also without serious side effects as it does not attack other body tissue or immune function. Yippee Yahoo !

** Speaking of immune function,  I wonder if anyone who has been prescribed DOCETAXEL has experience infections (i.e. seriously high temperature > 101'F / 38'C)  ?

Cheers,Sam. 

http://www.medicalnewstoday.com/articles/234240.php

http://www.thejournal.ie/drug-from-crocus-flower-could-destroy-tumours-224251-Sep2011/

http://www.bbc.co.uk/news/science-environment-14855666

http://www.ncbi.nlm.nih.gov/pubmed/20663911/

Cancer Res. 2010 Sep 1;70(17):6902-12. Epub 2010 Jul 27.

Development of a novel tumor-targeted vascular disrupting agent activated by membrane-type matrix metalloproteinases. Atkinson JM,Falconer RA, DR, Pennington CJ, Siller CS, Shnyder SD, Bibby MC, LH, Loadman PM, Gill JH.Source Institute of Cancer Therapeutics, University of Bradford, Bradford, West Yorkshire, UK.

Abstract

Vascular disrupting agents (VDA) offer a strategy to starve solidtumors of nutrients and oxygen concomitant with tumor shrinkage.Several VDAs have progressed into early clinical trials, but theirtherapeutic value seems to be compromised by systemic toxicity. Inthis report, we describe the design and characterization of a novelVDA, ICT2588, that is nontoxic until activated specifically in thetumor by membrane-type 1 matrix metalloproteinase (MT1-MMP). HT1080cancer cells expressing MT1-MMP were selectively chemosensitive toICT2588, whereas MCF7 cells that did not express MT1-MMP werenonresponsive. Preferential hydrolysis of ICT2588 to its activemetabolite (ICT2552) was observed in tumor homogenates of HT1080relative to MCF7 homogenates, mouse plasma, and liver homogenate.ICT2588 activation was inhibited by the MMP inhibitor ilomastat. InHT1080 tumor-bearing mice, ICT2588 administration resulted in theformation of the active metabolite, diminution of tumor vasculature,and hemorrhagic necrosis of the tumor. The antitumor activity ofICT2588 was superior to its active metabolite, exhibiting reducedtoxicity, improved therapeutic index, enhanced pharmacodynamic effect,and greater efficacy. Coadministration of ICT2588 with doxorubicinresulted in a significant antitumor response (22.6 d growth delay),which was superior to the administration of ICT2588 or doxorubicin asa single agent, including complete tumor regressions. Our findingssupport the clinical development of ICT2588, which achieves selectiveVDA targeting based on MT-MMP activation in the tumormicroenvironment.PMID:   20663911 ; PMCID: PMC2933508

J Clin Oncol. 2011 Aug 15. [Epub ahead of print]Chemotherapy-Based Treatment for Castration-Resistant Prostate Cancer. Seruga B, Tannock IFBostjan Seruga, Institute of Oncology Ljubljana, Ljubljana, Slovenia; and Ian F. Tannock, Princess Margaret Hospital and University of Toronto, Toronto, Ontario, Canada.

Abstract

Most men with metastatic prostate cancer respond to various types ofandrogen ablation but progress to castration-resistant disease. TheTAX 327 and Southwest Oncology Group (SWOG) 99-16 clinical trialsestablished docetaxel-based chemotherapy as preferred first-linetreatment for most men with symptomatic metastaticcastration-resistant prostate cancer (mCRPC). However, only about halfreceive benefit from docetaxel, and those who respond initiallyprogress and eventually die of (or with) mCRPC. Both cellularmechanisms and the tumor microenvironment are implicated in thedevelopment of resistance to docetaxel. New agents are being evaluatedfor men with mCRPC, either as first-line treatment in combination withdocetaxel, or in men progressing during or after treatment withdocetaxel. Thus far, agents evaluated in phase III trials incombination with docetaxel have not improved outcome, including thevaccine GVAX, high-dose vitamin D (DN-101), and the antiangiogenicagent bevacizumab. In contrast, cabazitaxel, a taxane that is notcross-resistant to docetaxel, substantially improved the outcome ofmen progressing during or after treatment with docetaxel-basedchemotherapy when compared with mitoxantrone and prednisone. However,translation of benefit of cabazitaxel demonstrated in the TROPIC(Treatment of Hormone-Refractory Metastatic Prostate Cancer) trialinto general oncologic practice will be challenging because this agentmay cause serious toxicity. With the approval of less toxic hormonalagents (eg, abiraterone acetate) in the setting of docetaxel-resistantmCRPC, clinicians will have an opportunity to balance benefits andharms of new agents in an individual patient and may be able to usedifferent agents in sequence. PMID: 21844499