Intermittent Versus Continuous Androgen Deprivation Therapy in Advanced Prostate Cancer

Klotz, Laurence

doi:10.1007/s11934-013-0325-x

Cited by 16 publications

(12 citation statements)

References 39 publications

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“…It has been suggested that patients who failed to achieve a PSA nadir <4 ng/ml after the induction period of 6 months should not be offered IAD [44]. Factors that influence testosterone recovery also include baseline TT [45]. Our study showed that, in the PCa population, there was a large variation in TT serum levels (range 5.50-40.70 nmol/l; table 1) which was independently associated with FT and pGS (table 4B).…”

Section: Discussionmentioning

confidence: 99%

Associations of Pretreatment Serum Total Testosterone Measurements with Pathology-Detected Gleason Score Cancer

Porcaro

Petrozziello²,

Ghimenton³

et al. 2013

Urol Int

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Background and Objective: Prostate cancer is an endocrine-dependent tumor which is still under-investigated for physiopathology factors related to its natural history. The association of pretreatment total testosterone (TT) serum levels with prostate cancer is still a controversial topic. The objective of this study was to investigate potential associations and functional relationships of preoperative TT serum level and pathology-detected Gleason score (pGS). Materials and Methods: Pretreatment and pathological variables of 220 patients operated with radical prostatectomy were retrospectively reviewed. Age, prostate-specific antigen (PSA), percentage of positive biopsy cores (P+), biopsy Gleason score (bGS), pGS, TT and free testosterone were the continuous variables, while clinical stage (cT: cT1c, cT2/3), biopsy Gleason pattern (bGP: ≤3+3, 3+4, >3+4), pathology Gleason pattern (pGP: ≤3+3, 3+4, >3+4), pathology stage (pT: pT2, pT3a, pT3b), pathology nodal staging (pN: pN0, pN1, pNx) and surgical margin invasion by cancer (R-, R+) were the categorical variables. Statistical methods were computed for assessing associations of TT and pGS; moreover, simple and multiple linear regression analysis (SLRA and MLRA) were used for assessing functional relationships of TT and pGS. Results: High-grade tumors (pGS ≥8.0) were associated with bGS >6.0 (p < 0.0001), pGP ≥3+4 (p < 0.0001), P+ >0.31% (p = 0.006), cT2/3 (p = 0.01), TT >15.5 nmol/l (p = 0.0004) and, to a lesser extent, PSA >6.27 μg/l (p = 0.06). The odds ratio (OR) ranked as follows: 2.01 (PSA >6.27 μg/l), 2.88 (cT2/3), 3.23 (P+ >0.31%), 5.53 (TT >15.5 nmol/l) and 12.09 (pGP ≥3+4 and pGS ≥8.0). On SLRA, pGS variation was significantly predicted by bGS (p < 0.0001), P+ (p < 0.0001), PSA (p = 0.0005) and TT (p = 0.02); on MLRA, pGS variation was still significantly predicted by bGS (p < 0.0001), P+ (p = 0.04), PSA (p = 0.03) and TT (p = 0.002). When bGS, P+, PSA and TT were dichotomized to their median value, only bGS (p < 0.0001) and TT (p = 0.001) showed independence in predicting pGS variation. The best model for predicting pGS variations was by dichotomizing TT above its median (>15.5 nmol/l) because the predictive coefficient increased to 0.32, which means that patients with TT >15.5 have a significantly higher estimated risk for high-grade pGS than patients with TT ≤15.5 nmol/l (OR = 1.31). Conclusion: In a patient population undergoing radical prostatectomy, increased pretreatment serum measurements of TT are associated with and functionally related to high-grade pGS; moreover, baseline TT together with bGS and PSA are important factors for predicting pGS and assessing high-grade tumors. Baseline TT serum levels might have prognostic potential for assessing treatment response for continuous as well as intermittent androgen deprivation therapy.

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Section: Discussionmentioning

confidence: 99%

Associations of Pretreatment Serum Total Testosterone Measurements with Pathology-Detected Gleason Score Cancer

Porcaro

Petrozziello²,

Ghimenton³

et al. 2013

Urol Int

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“…13 Recent reviews comparing efficacy, side effects, time to castration resistance, overall and cancer-specific survival between intermittent and continuous ADT have been summarised; however, the evidence regarding the tradeoffs between the benefits and risks of intermittent ADT remains inconclusive. [17][18][19][20][21][22][23] Generally the consensus is that overall survival is equivalent between intermittent and continuous ADT in most settings. However, concerns remain with high-risk disease, as one of the larger trials did not meet criteria for non-inferiority of an intermittent regimen in men with metastatic cancer.…”

Section: How Might This Impact On Clinical Practice?mentioning

confidence: 99%

International survey of androgen deprivation therapy (ADT) for non-metastatic prostate cancer in 19 countries.

Liede

Hallett

Hope

et al. 2015

JCO

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Background: Continuous androgen deprivation therapy (CADT) is commonly used for patients with non-metastatic prostate cancer as primary therapy for high-risk disease, adjuvant therapy together with radiation or for recurrence after initial local therapy. Intermittent ADT (IADT), a recently developed alternative strategy for providing ADT, is thought to potentially reduce adverse effects, but little is known about practice patterns relating to it. We aimed to describe factors related to physicians' ADT use and modality for patients with non-metastatic prostate cancer.Methods: A 45 min online survey was completed by urologists and oncologists responsible for treatment decisions for non-metastatic prostate cancer from 19 countries with high or increasing prevalence of nonmetastatic prostate cancer.Results: There were 441 treating physicians who completed the survey which represented 99 177 patients with prostate cancer under their care, of which 76 386 (77%) had non-metastatic prostate cancer. Of patients with non-metastatic prostate cancer, 38% received ADT (37% gonadotropin-releasing hormone (GnRH), 2% orchiectomy); among patients on GnRH, 54% received CADT (≥6 without >3 months interruption), 23% IADT and 23% <6 months. Highest rates of ADT were reported among oncologists (62%) and in Eastern Europe (Czech Republic, Hungary and Poland). Prostate-specific antigen (PSA) levels (65%), Gleason score (52%) and treatment guidelines (48%) were the most common reasons for CADT whereas PSA levels (54%), patient request (48%), desire to maintain sexual function (40%), patient age and comorbidities (38%) were cited most frequently as reasons for IADT.

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“…Recent studies on the treatment of advanced prostate cancer suggested that intermittent ADT might provide comparable survival to continuous ADT, with significant improvements in QOL (5). There have been considerable arguments regarding the benefit of continuous and maintenance chemotherapy after first response in other solid tumors (6,7).…”

Section: Introductionmentioning

confidence: 99%

A prospective multicenter study of intermittent chemotherapy with docetaxel and prednisolone for castration-resistant prostate cancer

Narita

Koie

Yamada

et al. 2016

Japanese Journal of Clinical Oncology

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Objective: The optimal schedule of docetaxel chemotherapy for castration-resistant prostate cancer is unknown, although continuous administration is accepted as the standard. We conducted a Phase II trial to evaluate the outcome of intermittent docetaxel and prednisolone therapy in castrationresistant prostate cancer. Methods: The patients were treated using a 28-day cycle of docetaxel (70 mg/m 2 on Day 1) and oral prednisolone (10 mg/day). After three consecutive administrations of docetaxel, a holiday was taken until prostate specific antigen levels returned to the baseline. The therapy was continued intermittently until the disease progressed, drug toxicity occurred, or the patients refused further treatment. The primary endpoint was overall survival. Time to treatment failure, adverse events, the duration of chemotherapy holiday and quality of life were also evaluated.Results: A total of 120 patients were enrolled. The median age and pretreatment prostate specific antigen level were 72 years and 37.5 ng/ml, respectively. Sixty (50.0%) patients resumed chemotherapy after the first holiday, and a maximum of six courses were administered to four patients. The median period of the first, second and third-to-fifth holiday was 18.6, 11.0 and 4.9 weeks, respectively. Toxicity was moderate, except for two fatal adverse events. The median time to treatment failure and overall survival from the initiation of docetaxel and prednisolone therapy in all patients were 17.5 and 35.0 months, respectively. All quality-of-life scores were unchanged statistically from the start of docetaxel and prednisolone therapy to the beginning of the second course. Conclusions: Intermittent docetaxel and prednisolone therapy might be a feasible treatment option for castration-resistant prostate cancer with comparable outcome and successful chemotherapy holidays.

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Intermittent Versus Continuous Androgen Deprivation Therapy in Advanced Prostate Cancer

Cited by 16 publications

References 39 publications

Associations of Pretreatment Serum Total Testosterone Measurements with Pathology-Detected Gleason Score Cancer

Associations of Pretreatment Serum Total Testosterone Measurements with Pathology-Detected Gleason Score Cancer

International survey of androgen deprivation therapy (ADT) for non-metastatic prostate cancer in 19 countries.

A prospective multicenter study of intermittent chemotherapy with docetaxel and prednisolone for castration-resistant prostate cancer

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