Severe neutropenia during cabazitaxel treatment is associated with survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of the TROPIC phase III trial

Meisel, Alexander; Felten, Stefanie von; Vogt, Deborah R; Liewen, Heike; Wit, Ronald de; Bono, Johann S. de; Sartor, Oliver; Stenner, Frank

doi:10.1016/j.ejca.2015.12.009

Cited by 65 publications

(58 citation statements)

References 27 publications

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“…опубликовали данные о наличии взаимосвязи между частотой развития ней-тропении ≥III степени тяжести и эффективностью терапии кабазитакселом [44]. В частности, медиана ОВ и ВБП пациентов, у которых на фоне терапии кабазитакселом развилась нейтропения ≥III степени тяжести составляла 16,3 и 4,6 мес соответственно по сравнению с пациентами, у которых не отмечено данного нежелательного явления, -14 и 2,1 мес.…”

Section: диагностика и лечение опухолей мочеполовой системы рак предunclassified

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis

et al. 2018

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ВведениеРак предстательной железы (РПЖ) является наи-более часто выявляемым некожным злокачественным заболеванием в США и Европе и одной из наиболее частых причин онкологической летальности [1]. Не-смотря на эффективность гормональной терапии (ГТ), у всех пациентов с метастатическим процессом рано или поздно отмечается прогрессирование заболева-ния -переход в кастрационно-резистентный РПЖ (КРРПЖ), который ассоциирован с плохим исходом. В 2004 г. по результатам 2 исследований препарат из группы таксанов доцетаксел был внесен в рекомен-дации как метод 1-й линии лечения метастатического КРРПЖ (мКРРПЖ), продемонстрировавший свою относительную безопасность и эффективность [2,3]. В случае дальнейшего прогрессирования возможности эффективного лечения были крайне ограничены. Не-сколько препаратов было оценено во II фазе исследо-ваний, однако показан лишь умеренный ответ -сни-жение уровня простатического специфического антигена (ПСА) на ≥50 % у 17-24 % пациентов. На се-годняшний день ввиду отсутствия улучшения выжи-ваемости и качества жизни больных эти препараты не рекомендуются в качестве терапии 2-й линии мКРРПЖ [4].Разработка и внедрение в клиническую практику препарата группы таксанов 2-го поколения стали сле-дующим шагом лечения мКРРПЖ [5].

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Section: диагностика и лечение опухолей мочеполовой системы рак предunclassified

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis

et al. 2018

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“…However, almost all ADT treatments eventually fail due to the development of metastatic castration-resistant prostate cancer (mCRPC). Recently, 'second-generation' drugs, such as enzalutamide (also named MDV3100), abiraterone acetate, and cabazitaxel, have been administered to patients who develop mCRPC 3-7. Enzalutamide is an AR antagonist which has an 8-fold higher affinity for AR than bicalutamide, and inhibits the ability of AR to translocate into the nucleus and bind DNA 8.…”

Section: Introductionmentioning

confidence: 99%

Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells

Han¹,

Huang²,

Liu³

et al. 2017

Theranostics

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Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown. In this study, we found that TPL at low dose inhibits the transactivation activity of both full-length and truncated AR without changing their protein levels. Interestingly, TPL inhibits phosphorylation of AR and its CRPC-associated variant AR-V7 at Ser515 through XPB/CDK7. As a result, TPL suppresses the binding of AR to promoter regions in AR target genes along with reduced TFIIH and RNA Pol II recruitment. Moreover, TPL at low dose reduces the viability of prostate cancer cells expressing AR or AR-Vs. Low-dose TPL also shows a synergistic effect with enzalutamide to inhibit CRPC cell survival in vitro, and enhances the anti-cancer effect of enzalutamide on CRPC xenografts with minimal side effects. Taken together, our data demonstrate that TPL targets the transactivation activity of both full-length and truncated ARs. Our results also suggest that TPL is a potential drug for CRPC, and can be used in combination with enzalutamide to treat CRPC.

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“…31 An ad-hoc analysis of the TROPIC trial demonstrated that patients who developed grade ≥3 neutropenia while receiving cabazitaxel had an improved survival (HR 0.65, 95%CI 0.43-0.97, p=0.035) and that low NLR is also independently associated with improved survival. 19 . However, in the C-EAP cohort, neither NLR nor development of grade ≥3 neutropenia influenced prognosis.…”

Section: Prognostic Factorsmentioning

confidence: 99%

“…A further sub-analysis of the experimental arm of the TROPIC trial also identified severe neutropenia during treatment as a favourable prognostic factor. 19 In a separate study of 47 patients treated with cabazitaxel, a pretreatment elevated neutrophil-to-lymphocyte ratio (NLR) greater than 3.83 was found to confer a worse prognosis with a HR of 3.0. 20 In routine clinical practice, little is known about the prognostic factors for patients receiving second-line chemotherapy including the impact of prior treatments.…”

Section: Introductionmentioning

confidence: 99%

“…21 A sub-analysis of the experimental arm of the TROPIC trial identified that in addition to being a favorable prognostic factor, severe neutropenia was also a predictor of response. 19 A high Gleason score (>=8) was shown to correlate with increased progression-free survival in a small retrospective study. 22 This would be consistent with the theory that more aggressive disease benefits from cabazitaxel.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic and predictive clinical factors in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel

Yokom

Stewart

Alimohamed³

et al. 2018

CUAJ

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Introduction: Cabazitaxel is one of several treatment options available for patients with metastatic castration-resistant prostate cancer who have progressed on docetaxel. Little is known about clinical factors that influence prognosis or treatment response for patients receiving cabazitaxel. Identifying prognostic and predictive factors could contribute to the optimal selection of patients for treatment after docetaxel. Methods: A retrospective review of patients enrolled on the cabazitaxel Canadian Early Access Program (C-EAP) was performed. Clinical factors were analyzed by univariable and multivariable Cox proportional hazards and logistic regression analysis to identify independent predictors of prognosis and response. Results: Forty-five patients from five centres in Canada were included in this study. On multivariable analysis, lower hemoglobin was associated with shorter survival. No other factors were independently associated with survival, prostate-specific antigen (PSA) response or primary PSA progression. Conclusions: Clinical factors predicting survival or treatment response were not identified for men with castration-resistant prostate cancer receiving cabazitaxel. Larger studies may be necessary to identify clinical factors and biomarkers that identify whether patients should or should not receive cabazitaxel.

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Severe neutropenia during cabazitaxel treatment is associated with survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of the TROPIC phase III trial

Cited by 65 publications

References 27 publications

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis

Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells

Prognostic and predictive clinical factors in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel

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