Phase 2 Randomized Study of Radiation Therapy and 3-Year Androgen Deprivation With or Without Concurrent Weekly Docetaxel in High-Risk Localized Prostate Cancer Patients

Carles, Joan; Gallardo, Enrique; Domènech, Montserrat; Font, Albert; Bellmunt, Joaquim; Figols, Mariona; Mellado, Begoña; Sáez, María Isabel Corbí; Suárez, Cristina; Méndez, María José; Maroto, Pablo; Luque, Raquel; Portugal, Teresa de; Aldabo, Ramón; Bonfill, Teresa; Morales-Bárrera, Rafael; García, J.A.; Maciá, Sonia; Maldonado, X.; Arnalot, Palmira Foro

doi:10.1016/j.ijrobp.2018.10.005

Cited by 7 publications

(10 citation statements)

References 26 publications

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“…Table 2 and 6 report on studies comparing RT with or without ADT and ADT duration [13][14][15][16][17][18]23,26,27,29,30,32,[65][66][67][68][69]. Table 3 and 7 compare different RT modalities (including BT) [11,12,[19][20][21][22]24,25,28,33,34, and table 4 and 8 compare different RP modalities [16,31,[93][94][95][96][97][98]. A separate table was created for studies reporting on RT with doses below 70Gy (supplementary table 9-10).…”

Section: Quantity Of Evidence Identifiedmentioning

confidence: 99%

“…Thirty-five studies performed comparisons of different schedules, or combinations of modalities in the context of RT as the principal curative therapy [11,12,[19][20][21][22]24,25,28,33,34,. The categories were EBRT vs EBRT + BT, EBRT/BT dose/fractionation/field size comparisons, and the addition of chemotherapy to RT as multimodality therapy.…”

Section: Radiotherapy-different Intertreatment Modalitiesmentioning

confidence: 99%

“…Three studies reported on the addition of chemotherapy [24,25,33], with EEP in the RTOG 9902 trial and docetaxel in the QRT-SOGUG phase 2b and RTOG 0521 trial [25,33]. The RTOG 0521 RCT showed improvement in OS with docetaxel compared to EBRT + ADT [24].…”

Section: Ebrt +/-Chemotherapymentioning

confidence: 99%

“…The GETUG-12 trial suggested an improved relapse-free survival with docetaxel + ADT vs ADT alone [110]. The phase 2b trial by Carles et al reported good tolerability of low weekly doses of docetaxel, but without benefits in 5-yr BFFS, PFS and OS [33]. Its successor, the RTOG 0512 trial, revised treatment schedules with adapted RT schemes and docetaxel instead of EEP [24].…”

Section: Studies In the Context Of Primary Radiotherapymentioning

confidence: 99%

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Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

et al. 2020

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Context. The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. Objective. To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 years of follow-up. Secondary oncological outcomes are prostate cancer specific mortality (PCSM), overall mortality (OM), biochemical recurrence and need for salvage treatment with ≥5 years of follow-up. Non-oncological outcomes are quality of life (QoL), functional outcomes and treatment-related side effects reported. Evidence acquisition. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and non-randomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (ISUP grade 4-5 [GS 8-10] or PSA >20 ng/mL or ≥cT2c) and/or locally advanced PCa (any PSA, cT3-4 or cN+, any ISUP grade/ GS score) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT) or multimodality treatment combining any of the local treatments above (+/-any systemic treatment). Risk of Bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed. Evidence synthesis. Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance and detection bias and low RoB for correction of initial PSA and biopsy GS. When comparing RP to EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (post-operative) RT and/or ADT respectively. High levels of evidence exist for EBRT treatment with several RCTs showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in GU toxicity and sexual dysfunction, and EBRT in bowel problems. Conclusion. Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, also EBRT + BT can be offered, despite more grade 3 toxicity. Interesting, for selected patients, e.g. with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will be mos...

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Section: Quantity Of Evidence Identifiedmentioning

confidence: 99%

Section: Radiotherapy-different Intertreatment Modalitiesmentioning

confidence: 99%

Section: Ebrt +/-Chemotherapymentioning

confidence: 99%

Section: Studies In the Context Of Primary Radiotherapymentioning

confidence: 99%

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Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

et al. 2020

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“…As a DNA-binding antineoplastic antibiotic, MTM has been used to treat several malignant diseases, such as advanced testicular carcinoma [14], chronic myeloid leukemia [15], hypercalcemia [16] and Ewing sarcoma [17]. MTM was also reported to decrease AR mRNA transcription by inhibiting Sp1 binding to the AR promoter [18] and enhance tumor sensitivity by targeting SP1 [19]. However, the biological effect of MTM on AR transcriptional activity and AR variants in PCa is unclear.…”

Section: Introductionmentioning

confidence: 99%

Mithramycin suppresses DNA damage repair via targeting androgen receptor in prostate cancer

et al. 2020

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The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and metastatic PCa treatment. However, the occurrence of aberrant expression, mutated or splice variants of AR confers resistance to androgen ablation therapy (ADT), radiotherapy or chemotherapy in AR-positive PCa. Therapeutic strategies that effectively inhibit the expression and/or transcriptional activity of fulllength AR, mutated AR and AR splice variants have remained elusive. In this study, we report that mithramycin (MTM), an antineoplastic antibiotic, suppresses cell proliferation and exhibits dual inhibitory effects on expression and transcriptional activity of AR and AR splice variants. MTM blocks AR recruitment to its genomic targets by occupying AR enhancers and causes downregulation of AR target genes, which includes key DNA repair factors in DNA damage repair (DDR). We show that MTM significantly impairs DDR and enhances the effectiveness of ionizing radiation or the radiomimetic agent Bleomycin in PCa. Thus, the combination of MTM treatment with RT or radiomimetic agents, such as bleomycin, may present a novel effective therapeutic strategy for patients with high-risk, clinically localized PCa.

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Reporting of tobacco use and tobacco-related analyses in cancer cooperative group clinical trials: a systematic scoping review

Eng¹,

Brual²,

Nagee³

et al. 2022

ESMO Open

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Phase 2 Randomized Study of Radiation Therapy and 3-Year Androgen Deprivation With or Without Concurrent Weekly Docetaxel in High-Risk Localized Prostate Cancer Patients

Cited by 7 publications

References 26 publications

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

Mithramycin suppresses DNA damage repair via targeting androgen receptor in prostate cancer

Reporting of tobacco use and tobacco-related analyses in cancer cooperative group clinical trials: a systematic scoping review

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