Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer

Sternberg, Cora N.; Dumez, Herlinde; Poppel, Hein Van; Skoneczna, Iwona; Sella, Avishay; Daugaard, Gedske; Gil, Thierry; Graham, John D.; Carpentier, Paul; Calabrò, Fabio; Collette, Laurence; Lacombe, Denis

doi:10.1093/annonc/mdn784

Cited by 111 publications

(59 citation statements)

References 17 publications

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“…Oblimersen added to docetaxel was associated with an increase in the incidence of grade ≥3 fatigue, mucositis, and thrombocytopenia. Major toxic events were reported in 22.8 and 40.7% of patients with docetaxel and docetaxel-oblimersen, respectively (44).…”

Section: Agents Under Developmentmentioning

confidence: 98%

Novel strategies in the treatment of castration-resistant prostate cancer (Review)

et al. 2012

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Abstract. Prostate cancer is the most common cancer in men in Europe and the United States, and the third leading cause of death from cancer in Europe. Survival of prostate cancer cells is dependent on the activation of androgen receptors (AR), that are overexpressed in this tumor. Furthermore, ~90% of prostate cancer patients that respond to first-line androgen deprivation therapy (ADT) undergo rapid progression. This condition is defined as castration-resistant prostate cancer (CRPC). Docetaxelbased regimens significantly improve overall survival (OS) in patients with CRPC and represent the only treatment strategy approved by the Food and Drug Administration (FDA). Recently, abiraterone (second hormonal therapy) and cabazitaxel (new taxane) have been shown to improve survival in patients with CRPC who progressed following docetaxel-based chemotherapy. Vaccine therapy has also been demonstrated to improve OS in patients with asymptomatic or minimally symptomatic metastatic CRPC. Additional therapeutic targets have been analyzed in prostate cancer, including apoptosis, angiogenic receptors, vitamin D and Src pathways. Several phase II studies are ongoing. The high frequency of prostate cancer-related metastatic bone disease has led to consider this pathway as a therapeutic target. To this end, several bone-targeted agents have been investigated, most notably zoledronic acid, which is highly effective at stabilizing the bone and preventing skeletal complications. More recently, a nuclear factor-β ligand (RANKL) inhibitor, denosumab, has been developed for the treatment of bone metastases.

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Section: Agents Under Developmentmentioning

confidence: 98%

Novel strategies in the treatment of castration-resistant prostate cancer (Review)

et al. 2012

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“…Pre vi o us pha se I and II tri als of ob li mer sen as a che mo sen si ti zing agent be fo re do ce ta xel the rapy ha ve yi el ded pro mi sing re sults. 24 Thus, Bcl-2 might be a po ten ti al sur ro ga te mar ker and a tar get mo lecu le for ta xa ne-ba sed tre at ments in HRPC.…”

Section: Discussionmentioning

confidence: 99%

Targeting Bcl-2 Protein to Enhance Chemosensitivity of Hormone Refractory Prostate Cancer Cell Line, DU-145 by a Synergistic Combination of Docetaxel and Gossypol

Uzunoğlu¹,

Karaca²,

Atmaca³

et al. 2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : Do ce ta xel has be co me the stan dard of ca re for hor mo ne-ref rac tory pros tate can cer (HRPC), ho we ver drug re sis tan ce and to xi city are still chal len ging in da ily can cer practi ce. The an ti-apop to tic path way cen te red aro und the Bcl-2 pro te in might be one of the res pon sib le path ways. Ad ding a se cond drug to do ce ta xel tre at ment is one of the most com mon ap pro ac hes to sol ve this prob lem. Goss ypol was re por ted to ha ve po tent an ti can cer ac ti vi ti es in pros ta te can cer. In this study, we se arc hed for the pos sib le syner gis tic cyto to xic/apop to tic ef fects of this com bi nati on tre at ment in hor mo ne-and drug re sis tant pros ta te can cer cell li ne, DU-145 vi a in hi bi ti on of Bcl-2 pro te in. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : XTT cell vi a bi lity as say was used to as sess cyto to xi city of the drugs alo ne and in com bi na ti on. For ve rif ying apop to sis, Cell De ath De tec ti on Eli sa Plus Kit and Cas pa se-Glo 3/7 as say we re used. Wes tern Blot analy sis for Bcl-2 pro te in was car ri ed out. R Re e s su ul lt ts s: : A no vel drug com bi na ti on of do ce ta xel and goss ypol re sul ted in a sig ni fi cant syner gis tic cyto to xic ac ti vity and apop to sis as com pa red to any sing le agent alo ne, in a do se-and ti me de pen dent manner, and al so sig ni fi cantly re du ced Bcl-2 pro te in le vels in DU-145, in doses that can be used cli nically. C Co on nc c l lu u s si i o on n: : Ad ding goss ypol to do ce ta xel as a com bi na ti on tre at ment in HRPC pa ti ents might be a so lu ti on for ta xa ne re sis tant pa ti ents. In hi bi ti on of Bcl-2 might be one of the un derl ying ro utes of ac ti vity for this com bi na ti on.K Ke ey y W Wo or rd ds s: : Docetaxel; gossypol; prostatic neoplasms Ö ÖZ ZE ET T A Am ma aç ç: : Do se tak sel, hor mo na di renç li pros tat kan se ri nin (HRPC) te da vi sin de stan dart te da vi ha li ne gel miş du rum da dır an cak ilaç di ren ci ve tok si si te so run la rı uy gu la ma da ha la mev cu di ye ti ni de vam et tir mek te dir. Apop toz kar şı tı olan Bcl-2 pro te i ni pros tat kan se rin de ilaç di ren cin den so rumlu yol lar dan bi ri ola bi lir. Bu so ru nu çöz mek için en çok kul la nı lan yön tem do se tak se le ikin ci bir ilaç ek le mek tir. Gos si po lün pros tat kan se rin de kuv vet li an ti-kan ser et ki gös ter di ği bil di ril miş tir. Bu ça lış ma da, DU-145 ad lı hor mo na ve ila ca di renç li pros tat kan ser hüc re si di zi sin de, do se taksel/gos si pol kom bi nas yo nu nun Bcl-2 pro te in in hi bis yo nu yo luy la gös te re bi le ce ği ola sı si ner jik sito tok sik/apop to tik et ki yi araş tır dık. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : İlaç la rın tek ba şı na ve kom bi nas yon ha lin de hüc re ler üze rin de yap tı ğı tok sik et ki, hüc re can lı lı ğı nı be lir le yen XTT yön te miy le araş tı -rıl dı. Apop to zu doğ ru la mak için Cell De ath De tec ti on Eli...

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“…Sınıf 3 ve üzeri olgulardaki yan etkiler tedavi grupları arasında dengede iken, dosetaksel + oblimersen grubunda, güvenlik profili (temel olarak yorgunluk, mukoza iltihabı ve hematolojik toksisite) dosetaksel grubuna göre kötüye gitmiştir. Dolayısıyla, klinik çalışma sonlandırılmıştır (14). Gossypol (AT-101) Pamuk bitkisinden elde edilen doğal fenol bileşik olan gossypol, oral BH-3 mimetik ve pan-Bcl-2 inhibitörü olarak AT-101 jenerik ismiyle geliştirilmiştir.…”

Section: İçsel Yolak İnhibitörleriunclassified

Prostat Kanseri Tedavisinin Geleceği Apoptotik İndükleyicilerde mi?

Konac¹,

Sözen²

2017

uob

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Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer

Abstract: The primary end points of the study were not met: a rate of confirmed PSA response >30% and a major toxic event rate <45% were not observed with docetaxel-oblimersen.

Cited by 111 publications

References 17 publications

Novel strategies in the treatment of castration-resistant prostate cancer (Review)

Novel strategies in the treatment of castration-resistant prostate cancer (Review)

Targeting Bcl-2 Protein to Enhance Chemosensitivity of Hormone Refractory Prostate Cancer Cell Line, DU-145 by a Synergistic Combination of Docetaxel and Gossypol

Prostat Kanseri Tedavisinin Geleceği Apoptotik İndükleyicilerde mi?

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