8 juli 2012: dat chemo bij prostaatkanker effectief zou zijn staat wel ter discussie. Dat aanvullende calcitriol, een vorm van vitamine D wel een rol kan spelen wordt steeds aannemelijker. Als aanvulling op onderstaande informatie staat onderaan een abstract plus deeplink naar gratis in te zien volledig studierapport over vitamine D bij prostaatkanker.

12 juli 2004: FDA geeft toestemming Taxotere te gebruiken als medicijn bij uitbehandelde prostaatkankerpatiënten. Lees meer daarover verderop.

1/10/2002: onder dit bericht een studie calcitriol uit Pubmed toegevoegd:

30/9/2002: Onderzoekers aan de Oregon Health and Science University hebben een grootschalige gerandomiseerde dubbelblinde studie opgezet naar het effect van vitamine D -calcitriol -als aanvulling op de chemo docetaxel (taxotere) nadat uit een eerdere studie is gebleken dat deze aanvulling met calcitriol bij 81% van de deelnemende prostaatkankerpatiënten de PSA waarde voor meer dan 50% verminderde tegenover een PSA vermindering van 38 tot 46% met 50% of meer bij prostaatkankerpatiënten in vier studies met alleen docetaxel. Een verdubbeling van het resultaat dus. Interessant is natuurlijk dat als een prostaatkankerpatiënt overstapt op het Houtsmullerdieet met als aanvulling bepaalde voedingssuppletie, waaronder vitamine E en D enz. de PSA waarde vaak ook drastisch naar beneden gaat. Althans dat hebben we nu al van verschillende patiënten gehoord. Bovendien lijkt Prostasol, opvolger van PC-Spes, de goede werking van PC-Spes te bevestigen. Belangrijk is natuurlijk wel dat onderstaande studie uitgaat van vergevorderde prostaatkanker dus waarschijnlijk met uitzaaiingen in de botten.

19/09/02 - Researchers at the Oregon Health & Science University in the US on Thursday announced the launch of a national study to investigate the effect of high-dose vitamin D in combination with the chemotherapy agent docetaxel (Taxotere), for patients with advanced prostate cancer. 

The ASCENT (AIPC Study of Calcitriol Enhancing Taxotere) study is a multicentre, randomised, double-blind trial based on the results of a preliminary study in Oregon. ASCENT will determine whether a high dose of an active form of vitamin D, called calcitriol, taken once a week in combination with docetaxel, is any more effective than docetaxel alone for patients with androgen-independent prostate cancer (AIPC), an advanced form of prostate cancer. 
"Late-stage prostate cancer patients have few treatment options, and we are cautiously hopeful that this study will further confirm and extend the promising results we've already seen with docetaxel in combination with high-dose pulse administration (HDPA) calcitriol," said OHSU Cancer Institute oncologist Tomasz Beer, study chairman and assistant professor of medicine (hematology and medical oncology) in the OHSU School of Medicine. 

The study will enroll approximately 232 patients at about 20 medical centres in the United States, including OHSU. Additional sites will be added during the next several months. 

The study hopes to achieve a reduction of 50 per cent or more in prostate specific antigen (PSA) levels in patients. PSA is a substance produced within the prostate gland, and a high PSA level may indicate the presence of cancer. In patients with advanced prostate cancer, many clinicians use elevated PSA levels as an indicator of disease progression.

Results from the initial OHSU study were presented by Beer at the American Society of Clinical Oncology conference last May. In that trial, 81 per cent (30 of 37) of patients treated with HDPA calcitriol in combination with docetaxel had a reduction in PSA levels of more than 50 per cent. Four other studies of docetaxel without calcitriol have reported that 38 per cent to 46 per cent of the patients had more than a 50 per cent reduction in PSA levels, about half the rate as those patients on the combination therapy. 

Prostate cancer is the most common cancer in men, with approximately 189,000 new cases diagnosed and roughly 30,200 deaths in the United States each year (2002 Cancer Facts and Figures, American Cancer Society).

Further information on the study can be obtained from Martin Munguia at the Oregon Health & Science University: munguiam@ohsu.edu

  1/10/2002: Een bezoeker van de site en zelf een prostaatkankerpatiënt die al jaren naar zijn zeggen calcitriol gebruikt stuurde me deze studie op over hoge doses calcitriol. Waarvoor dank.

Urology 2002 Sep;60(3 Suppl 1):123-30; discussion 130-1

Vitamin D receptor: a potential target for intervention.

Johnson CS, Hershberger PA, Bernardi RJ, Mcguire TF, Trump DL Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. johnsoncs@msx.upmc.edu

Epidemiologic data suggest that low exposure to vitamin D or 1alpha,25-dihydroxycholecalciferol (calcitriol) increases the risk of prostate cancer. Calcitriol, a central factor in bone and mineral metabolism, is also a potent antiproliferative agent in a wide variety of malignant cell types. We have demonstrated that calcitriol has significant antitumor activity in vitro and in vivo in prostate and squamous cell carcinoma model systems. Calcitriol, in these models, induces a significant G0/G1 arrest and modulates p21(Waf1/Cip1) and p27(Kip1), the cyclin-dependent kinase inhibitors. Calcitriol induces poly (adenosine diphosphate-ribose) polymerase cleavage, increases bax/bcl-2 ratio, reduces levels of phosphorylated mitogen-activated protein kinases (P-MAPKs; also known as extracellular signal-related kinase 1/2) and phosphorylated Akt, induces caspase-dependent mitogen-activated protein kinase kinase (MEK) cleavage and upregulation of MEK kinase-1, all potential markers of the apoptotic pathway. We also have demonstrated that dexamethasone (dex) potentiates the antitumor effect of calcitriol through effects on the vitamin D receptor and decreases calcitriol-induced hypercalcemia. We initiated phase 1 and phase 2 trials of calcitriol, either alone or in combination with carboplatin, paclitaxel, or dex. Data from these studies indicate that high-dose calcitriol is feasible on an intermittent schedule, the maximum tolerated dose (MTD) is unclear, and dex or paclitaxel appear to ameliorate hypercalcemia. Studies continue to define the MTD of calcitriol on this intermittent schedule, either alone or with other agents, and to evaluate the mechanisms of calcitriol effects in prostate cancer models.

Novel vitamin D analogs for prostate cancer therapy

Source: 2011;2011:301490. Epub 2011 Sep 19. Reed full study report>>>>>>

Published online 2011 September 19. doi:  10.5402/2011/301490
PMCID: PMC3195751

Novel Vitamin D Analogs for Prostate Cancer Therapy

Abstract

Prostate cells contain specific receptors for 1α,25-dihydroxyvitamin D [1α,25(OH)2D] or calcitriol, the active form of vitamin D. 1α,25(OH)2D is known to inhibit the proliferation and invasiveness of prostate cancer cells. These findings support the use of 1α,25(OH)2D for prostate cancer therapy. However, 1α,25(OH)2D can cause hypercalcemia, analogs of 1α,25(OH)2D that are less calcemic but exhibit potent antiproliferative activity would be attractive as therapeutic agents. To accomplish these goals, different strategies, based on metabolism, molecular mechanism of actions, and structural modeling, have been taken to modify the structure of vitamin D molecule with the aims to improve the efficacy and decrease the toxicity of vitamin D to treat different diseases. During the past four decades, over 3,000 analogs have been synthesized. In this paper, we discuss the development and the biological analysis of a unique class of vitamin D analogs with a substitution at the carbon 2 of 19-nor-1α,25(OH)2D3 molecule for potential application to the prevention and treatment of prostate cancer as well as other cancers.

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