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3 februari 2012: in 2008 zijn de resultaten van een gerandomiseerde fase III studie naar het effect van Atrasentan bij prostaatkankerpatiënten vrijgegeven. Met een verrtaging van de progressie van de ziekte met 80 tot 100 dagen voor Atresentran t.o.v. placebo zijn er inmiddels betere medicijnen op de markt maar willen wij u deze informatie toch niet onthouden. Als u hier klikt kunt u het volledige studierapport gratis inzien. Hier het abstract ervan:

Cancer. 2008 Nov 1;113(9):2478-87.

Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer.

Nelson JB, Love W, Chin JL, Saad F, Schulman CC, Sleep DJ, Qian J, Steinberg J, Carducci M; Atrasentan Phase 3 Study Group.

Source

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15232, USA. nelsonjb@upmc.edu

Abstract

BACKGROUND:

Atrasentan is a potent, oral, selective endothelin-A (ET(A)) receptor antagonist that has clinical activity in patients with hormone-refractory prostate cancer (HRPC). In this article, the authors report the results from a phase 3, randomized, double-blind, placebo-controlled trial of atrasentan in patients with nonmetastatic HRPC.

METHODS:

Of 941 patients who had adequate androgen suppression and no radiographic evidence of metastases but rising prostate-specific antigen (PSA) levels, 467 patients were randomized to receive atrasentan at a dose of 10 mg, and 474 patients were randomized to receive placebo daily. The primary endpoint was the time to disease progression (TTP), which was defined as the onset of metastases. Secondary endpoints were the time to PSA progression, change in bone alkaline phosphatase (BALP) levels, PSA doubling time, and overall survival.

RESULTS:

There was a 93-day delay in the median TTP with atrasentan, but the difference from placebo in TTP was not statistically significant (P= .288). Large geographic differences in the median TTP were noted: in the US: The difference was 81 days longer with placebo; whereas, in non-US sites, the difference was 180 days longer with atrasentan. Atrasentan lengthened the PSA doubling time (P= .031) and slowed the increase in BALP (P< .001). The median survival was 1477 days with atrasentan and 1403 days with placebo. The most common adverse events associated with atrasentan were peripheral edema, nasal congestion, and headache, consistent with the vasodilatory properties of ET(A) receptor antagonists.

CONCLUSIONS:

Although the primary endpoint was not achieved, large regional differences in TTP were noted, suggesting that trial conduct may have influenced the results. The biologic activity was consistent with findings from other clinical trials of atrasentan in HRPC.

Bron: 4 juni 2004

Johns Hopkins Medicine
Office of Communications and Public Affairs
Media Contact: Vanessa Wasta
410-955-1287
wastava@jhmi.edu

Nu Asco weer begint, van 5 t/m 12 juni 2004, komen de publicaties weer los over veelbelovende medicijnen bij verschillende soorten kanker. Hier een studie over het middel Atrasentan dat bij prostaatkankerpatiënten zou voorkomen dat er uitzaaiingen plaatsvinden. Er wordt gesproken over 20% minder kans en minder pijn. Dit resultaat is een samenvoeging van fase II en III studieresultaten en zijn o.i. niet voor niets samengevoegd. De gecombineerde fase II en III studies zijn drie jaar lang gedaan met als vergelijking atrasentan met een placebo. Wie verder leest ziet echter dat er een onwezenlijk groot verschil zit tussen de resultaten uit de fase II studie en die uit de fase III studie. De fase II studie volgde 244 patiënten met gemetasteerde prostaatkanker en daarvan bleek Atrasentan bij 52% van de deelnemende patiënten een vertraging van de groei te zien te geven. Let wel hier wordt ook niet gesproken over totale remissies of worden PSA waarden genoemd als bewijs. De fase III studie bij 804 gemetasteerde prostaatkankerpatiënten liet echter geen enkel verschil zien in progressie van de ziekte. Zie deze passage uit persbericht zoals dat op Asco 5 juni 2004 wordt gepresenteerd.

The phase II trial enrolling 244 patients with metastatic hormone refractory prostate cancer was completed in 2001, and showed atrasentan delayed disease progression by 52 percent as compared to men receiving a placebo. Analysis of the phase III data alone did not show a difference in disease progression between the 804 patients randomized to receive atrasentan or the placebo. But when combined with the results of the Phase II study, investigators observed a statistically significant difference between the drug and its control in the length of time it took for the disease to progress. Both randomized, double-blind studies were similar in design and enrolled patients with hormone resistant prostate cancer that had metastasized or spread.

Voor de presentatie op ASCO hebben de onderzoekers dus maar gemakshalve de resultaten uit de twee studiefases bij elkaar gevoegd en zeggen nu dat er wel degelijk een significant resultaat is geboekt. Wat wij ons dan afvragen is waarom er niet uitvoerig wordt toegelicht hoe dat grote verschil in resultaat tussen de ene en andere studie is ontstaan terwijl naar hun zeggen precies dezelfde soort patiënten zijn gebruikt met compleet zelfde protocol. Dit persbericht en studieresultaat roep heel veel vraagtekens op bij ons.

Wie PC-Spes en prostasol kent weet dat deze middelen waarschijnlijk niet op Asco worden gepresenteerd maar in de praktijk bijzonder effectief lijken in het afremmen van prostaatkanker, al kunnen deze middelen ook niet zorgen voor definitieve genezing van prostaatkanker tot nu toe,

Hier het persbericht van ASCO:

June 3, 2004

EMBARGOED FOR RELEASE ON SATURDAY, JUNE 5, AT 5:30 P.M. EDT

PROSTATE CANCER PILL MAY STAVE OFF DISEASE AND EASE PAIN

Recent clinical studies led by Johns Hopkins Kimmel Cancer Center researchers have found that a drug called atrasentan reduces the risk by 20 percent that cancer will progress in men with advanced hormone-resistant prostate cancer. The results are expected to be presented at the 40th Annual American Society of Clinical Oncology (ASCO) meeting on June 5 in New Orleans.

"Treatment options remain limited for patients whose prostate cancer has spread and does not respond to hormone therapy, and some of these men are looking for less toxic alternatives than chemotherapy at this point in their lives," says Michael Carducci, M.D., associate professor at the Johns Hopkins Kimmel Cancer Center. "Atrasentan can help prevent their pain and may potentially postpone when they need more aggressive treatments like chemotherapy or radiation."

Combined results of phase II and phase III international clinical trials, which spanned three years and enrolled more than 1,000 men, showed an approximately 20 percent decrease in the chance that cancer will progress in those who took atrasentan daily versus a placebo.

"This drug's largest effect may be its ability to stabilize the progression of prostate cancer to the bone," says Carducci. "As a result, atrasentan slows the rise in PSA levels and delays the development of pain while maintaining quality of life." Few patients experienced side effects such as a stuffy nose, headache, and swelling.

Part of a new trend in cancer treatment, known as "targeted therapy," atrasentan blocks a protein called endothelin, which is secreted in excess amounts by prostate cancer cells. Endothelin promotes cancer cell growth and stimulates new bone formation where prostate cancer cells have spread to bone sites. Recent studies elsewhere confirm that endothelin is a key protein involved in the type of bone metastasis that commonly occurs in prostate cancer.

The phase II trial enrolling 244 patients with metastatic hormone refractory prostate cancer was completed in 2001, and showed atrasentan delayed disease progression by 52 percent as compared to men receiving a placebo. Analysis of the phase III data alone did not show a difference in disease progression between the 804 patients randomized to receive atrasentan or the placebo. But when combined with the results of the Phase II study, investigators observed a statistically significant difference between the drug and its control in the length of time it took for the disease to progress. Both randomized, double-blind studies were similar in design and enrolled patients with hormone resistant prostate cancer that had metastasized or spread.

Carducci plans to continue studies of atrasentan in patients whose cancer has not spread and in combination with other drugs that block growth factors. He adds that atrasentan could potentially be an option after second-line hormonal therapy or when patients are waiting to begin chemotherapy. Johns Hopkins and other centers nationwide will study the drug in patients with brain, renal cell, ovarian and lung cancers. The identification of endothelin and its role in prostate cancer as a potential target for therapy led to the development of atrasentan and was first described nine years ago in Johns Hopkins laboratories through a specialized program of research excellence (SPORE) grant from the National Cancer Institute.

Co-authors are Joel B. Nelson from the University of Pittsburgh, F. Saad from University of Montreal, Canada; C.C. Schulman from Erasme Hospital, Brussels, Belgium; D.P. Dearnaley from Royal Marsden Hospital, London; D.J. Sleep, S.M. Hulting, J.D. Isaacson, A.R. Allen, and P. Nisen from Abbott Laboratories.

This study was funded by Abbott Laboratories.

Carducci is a consultant to Abbott Laboratories. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

Abstract #4508, Proceedings of the American Society of Clinical Oncology.

Links:
Johns Hopkins Kimmel Cancer Center:
http://www.hopkinskimmelcancercenter.org
American Society of Clinical Oncology: http://www.asco.org