Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer (DRPC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 172-172
Author(s):  
C. W. Reuter ◽  
M. A. Morgan ◽  
V. Gruenwald ◽  
M. Fenner ◽  
P. Ivanyi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Testosterone ◽  
Salvage Chemotherapy ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Testosterone Levels ◽  
Grade 3 ◽  
Docetaxel Chemotherapy

172 Background: Cabacitaxel has recently been approved by the FDA as second-line chemotherapy for patients progressing during or after first-line docetaxel chemotherapy. However, cabacitaxel treatment is hampered by high costs and toxicity. Carboplatin in combination with docetaxel may also be effective in DRPC. Platinum(II)-complexes have been shown to lower testosterone levels by inhibiting 3β-hydroxysteroid dehydrogenase and 17α hydroxylase (Schertl et al. J Cancer Res Clin Oncol. 2007;133:153-67). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 55 consecutive DRPC pts were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) plus prednisone 2×5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone levels were measured before and during carboplatin/docetaxel chemotherapy (n=25). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 28/55 (50.9%) patients. At the time of the current analysis the median follow-up time was 11.9 months and 32/55 patients had died. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.7, 9.3) and median overall survival (OS) was 17.1 months (CI 95% 10.3, 23.9). In PSAR, PFS was 13.6 (CI 95% 7.8, 19.4) months versus 4.3 (CI 95% 2.9, 5.7) months in PSANR (p<0.001; hazard ratio HR 0.159) and OS was 24.4 months (CI 95% 18.1, 30.8) versus 8.1 (CI 95% 3.4, 12.8) months (p<0.001; HR 0.208). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (44.2/40.4%). Median free testosterone levels were 1.05 pg/ml before and 0.26 pg/ml during carboplatin/docetaxel treatment (p<0.01). Conclusions: Our data suggest that carboplatin/docetaxel may be an important therapeutic second-line treatment option for DRPC patients by inferfering with the testosterone synthesis. No significant financial relationships to disclose.

Hormonal impact of salvage chemotherapy with carboplatin plus weekly docetaxel in patients with castration- and docetaxel-resistant prostate cancer (DRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 74-74
Author(s):  
Christoph W. Reuter ◽  
Michael A. Morgan ◽  
Martin Fenner ◽  
Viktor Grünwald ◽  
Arnold Ganser
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Testosterone ◽  
Salvage Chemotherapy ◽  
Testosterone Levels ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Testosterone Biosynthesis ◽  
Grade 3

74 Background: Recent data suggest that carboplatin may be effective in combination with docetaxel in DRPC. Platinum(II)-complexes have been shown to interfere with testosterone biosynthesis by inhibiting the cholesterol side chain cleavage enzyme (CYP11A1), 3b-hydroxysteroid dehydrogenase (HSD3B1,2) and 17a hydroxylase/C17,20-lyase (CYP17A1). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 68 consecutive DRPC pts were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone levels were measured before (n=42) and during DC treatment (n=36). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 32/68 (47.1%) patients. At the time of the current analysis the median follow-up time was 13.6 months and 43/68 patients had died. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.4, 9.5) and median overall survival (OS) was 18.6 months (CI 95% 12.3, 24.9). In PSAR, PFS was 15.7 versus 4.8 months in PSANR (p<0.001; hazard ratio HR 0.19, CI 0.09, 0.39) and OS was 25.6 versus 8.1 months (p<0.001; HR 0.21 CI 0.10, 0.42). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (39.7/33.8%). Median free testosterone levels were 0.935 pg/ml before and 0.185 pg/ml during DC treatment (nadir; p<0.001). While free testosterone levels before DC treatment were associated with lower PSAR (HR 6.32 CI 1.60, 25,0; p=0.009), free testosterone nadir levels <0.18 pg/ml during DC treatment were associated with higher PFS (HR 0.126 CI 0.04, 0.46, p=0.002) and OS (HR 0.07 CI 0.008, 0.53; p=0.01). Conclusions: These data suggest that DC may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.

Hormonal impact of salvage chemotherapy with carboplatin plus weekly docetaxel in patients with castration- and docetaxel-resistant prostate cancer (DRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15190-e15190
Author(s):  
Christoph W. Reuter ◽  
Michael A. Morgan ◽  
Martin Fenner ◽  
Philipp Ivanyi ◽  
Viktor Grünwald ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Detection Limit ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Testosterone ◽  
Salvage Chemotherapy ◽  
Testosterone Levels ◽  
Weekly Docetaxel ◽  
Median Serum ◽  
Grade 3

e15190 Background: Recent data suggest that carboplatin may be effective in combination with docetaxel in DRPC. Platinum(II)-complexes interfere with steroid biosynthesis lowering testosterone levels by inhibiting CYP11A1, HSD3B1,2 and CYP17A1. Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2007) criteria. Since February 2005, 68 consecutive DRPC pts were treated with at least two cycles of carboplatin (C) AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel (D) at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG recommendations. Free testosterone levels were measured before (n=42) and during DC chemotherapy (n=36). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 32/68 (47.1%) patients. At the time of the current analysis (9/30/11) the median follow-up time was 13.6 months, 42/68 patients had died and 48/68 had progressive disease. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.4, 9.6) and median overall survival (OS) was 18.6 months (CI 95% 11.7, 25.5). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (45.6/39.7%). Median free testosterone levels were 0.935 pg/ml before and 0.185 pg/ml during DC treatment (nadir levels, p<0.001; detection limit <0.18 pg/ml). Median serum androgene levels (T+DHT) were 0.26 ng/ml before and below the detection limit of <0.05 ng/ml during DC treatment (median nadir levels). While free testosterone levels before DC treatment were associated with lower PSAR (HR 6.32 CI 1.60, 25,0; p=0.009), free testosterone nadir levels <0.18 pg/ml during DC treatment were associated with higher PFS (HR 0.126 CI 0.04, 0.46, p=0.002) and OS (HR 0.07 CI 0.01, 0.59; p=0.014). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.

Prognostic value of free testosterone (FT) levels during salvage chemotherapy with carboplatin plus weekly docetaxel in metastatic castration- and docetaxel-resistant prostate cancer (mDRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 152-152
Author(s):  
Christoph W. Reuter ◽  
Michael A. Morgan ◽  
Martin Fenner ◽  
Viktor Grünwald ◽  
Arnold Ganser
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Testosterone ◽  
Salvage Chemotherapy ◽  
Blood Levels ◽  
Weekly Docetaxel ◽  
Grade 3 ◽  
The Impact

152 Background: Recent data suggest that carboplatin plus weekly docetaxel (DC) may be effective in mDRPC. Carboplatin, docetaxel and steroids interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone blood levels was analyzed. Methods: Docetaxel failure/resistance was defined as disease progression during docetaxel treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC patients (pts.) were treated with at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 plus docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) every 4 weeks and prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. FT levels were measured before (n=50) and during DC chemotherapy (n=43). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 35/74 (47.3%) pts. At the current analysis the median follow-up time was 16.0 months and 54/74 pts. had died. Median progression-free survival (PFS) was 6.9 months (CI 95% 5.3, 8.4) and median overall survival (OS) was 18.6 months (CI 95% 12.4, 24.7). Median nadir FT levels were 2.8 pmol/L before and below the RIA detection limit of 0.6 pmol/L during DC treatment (p=0.011). While only 4/50 pts. had FT levels <0.6 pmol/L before DC treatment (all under abiraterone therapy), 27/43 pts. had nadir FT values <0.6 pmol/L during DC chemotherapy (p<0.001). FT levels <1 pmol/L during DC treatment were associated with a higher PSA response rate (hazard ratio HR 0.09; CI 0.02, 0.81, p=0.032) and FT levels <0.6 pmol/L with a higher OS (HR 0.45; CI 0.18, 0.98, p=0.045). FT remained statistically prognostic in multivariable analyses. The DC regimen was reasonably well tolerated, with leukopenia/ neutropenia as the most common reversible grade 3/4 toxicity (41.9/37.8%). Conclusions: These data demonstrate for the first time that FT is an important prognostic factor for PSAR and OS in mDRPC pts. receiving chemotherapy.

Salvage chemotherapy with carboplatin plus weekly docetaxel in patients (pts) with castration- and docetaxel-resistant prostate cancer (DRPC): Associations of patient and disease characteristics with overall survival (OS).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 75-75
Author(s):  
Christoph W. Reuter ◽  
Michael A. Morgan ◽  
Viktor Grünwald ◽  
Christoph A. J. von Klot ◽  
Axel S. Merseburger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Detection Limit ◽  
Objective Response ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Testosterone ◽  
Salvage Chemotherapy ◽  
Disease Response ◽  
Testosterone Levels ◽  
Weekly Docetaxel

75 Background: Our recent data suggest that carboplatin is effective in combination with docetaxel (DC) in docetaxel-resistant prostate cancer (DRPC). Platinum(II)-complexes interfere with steroid biosynthesis lowering testosterone levels by inhibiting the cholesterol side chain cleavage enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase (HSD3B1,2) and 17α hydroxylase/C17,20-lyase (CYP17A1). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Treatment consisted of at least two cycles of carboplatin AUC5 iv for 30 min on day one every 4 weeks (q4w), docetaxel 35 mg/m2 iv for one hour on days 1, 8, and 15 plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone levels were measured before (n=59) and during DC chemotherapy (n=52). Results: Of the 82 pts treated since February 2005, 95.1% had bone, 42.7% had lymph node, 26.8% liver, and 18.3% lung involvement. At the current analysis, the median follow-up time was 15.6 months. The objective response rate was 40.8% and the disease control rate 63.3% in the 49 pts with measureable disease. Response of prostate-specific antigen (greater than or equal to 50%) was observed in 3 out of /82 (47.6%) pts. Median progression-free survival (PFS) was 6.9 months (CI 95% 6.0, 7.8) and median OS was 18.0 months (CI 95% 12.7, 23.3). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (42.7/37.8%). Median free testosterone (fT) was 0.745 pg/ml before and less than 0.18 pg/ml during DC treatment (nadir levels, p=0.009; detection limit less than 0.18 pg/ml) and median serum androgene (T+DHT=TA) was 0.19 ng/ml and below the detection limit of less than 0.05 ng/ml (p<0.001). In multivariate analyses, lactate dehydrogenase, PSA response, and fT and TA nadir levels were associated with longer OS (p<0.05). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.

Prognostic value of free testosterone (FT) levels during salvage chemotherapy with carboplatin plus weekly docetaxel in metastatic castration- and docetaxel-resistant prostate cancer (mDRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16024-e16024
Author(s):  
Christoph W. Reuter ◽  
Michael A. Morgan ◽  
Martin Fenner ◽  
Viktor Grünwald ◽  
Arnold Ganser
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Testosterone ◽  
Salvage Chemotherapy ◽  
Blood Levels ◽  
Weekly Docetaxel ◽  
Grade 3 ◽  
The Impact

e16024 Background: Recent data suggest that carboplatin plus weekly docetaxel (DC) may be effective in mDRPC. Carboplatin, docetaxel and steroids interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone blood levels was analyzed. Methods: Docetaxel failure/resistance was defined as disease progression during docetaxel treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC patients (pts.) were treated with at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 plus docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) every 4 weeks and prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. FT levels were measured before (n=51) and during DC chemotherapy (n=41). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 36/74 (48.6%) pts. At the current analysis the median follow-up time was 16.6 months and 56/74 pts. had died. Median progression-free survival (PFS) was 6.9 months (CI 95% 5.9, 7.9) and median overall survival (OS) was 18.6 months (CI 95% 12.4, 24.7). Median nadir FT levels were 2.8 pmol/L before and below the RIA detection limit of 0.6 pmol/L during DC treatment (p=0.008). While only 4/51 pts. had FT levels <0.6 pmol/L before DC treatment (all under abiraterone therapy), 28/41 pts. had nadir FT values <0.6 pmol/L during DC chemotherapy (p<0.0001). Median FT levels <0.9 pmol/L during DC treatment were associated with a higher PSA response rate (hazard ratio HR 0.19; CI 0.05, 0.78, p=0.021) and a higher OS (HR 0.34; CI 0.15, 0.81, p=0.015). FT remained statistically prognostic in multivariable analyses. The DC regimen was reasonably well tolerated, with leukopenia/ neutropenia as the most common reversible grade 3/4 toxicity (41.9/37.8%). Conclusions: These data demonstrate for the first time that FT is an important prognostic factor for PSAR and OS in mDRPC pts. during chemotherapy.

scholarly journals Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Noriyoshi Miura ◽  
Nozomu Tanji ◽  
Yutaka Yanagihara ◽  
Terutaka Noda ◽  
Seiji Asai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Gastric Bleeding ◽  
Castration Resistant ◽  
Analgesic Agents ◽  
Grade 3

Aim: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. Methods: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. Results: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. Conclusion: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

Phase III study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): The ARCHES trial.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 687-687 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Russell Zelig Szmulewitz ◽  
Daniel Peter Petrylak ◽  
Arnauld Villers ◽  
Arun Azad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
High Volume ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3

687 Background: ENZA, a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Efficacy of ENZA with ADT in men with mHSPC is unknown. Methods: ARCHES is a multinational, double-blind, phase 3 study (NCT02677896). Patients (pts) with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was radiographic progression-free survival (rPFS) assessed centrally or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n=574) or PBO (n=576); baseline characteristics were balanced between groups. Overall, 67% had distant metastasis at initial diagnosis; 63% had high volume disease, 18% had prior docetaxel. Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, pattern of spread, region and prior docetaxel (HRs 0.24–0.53). Secondary endpoints improved with ENZA + ADT (Table); OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs PBO + ADT in men with mHSPC, with a preliminary safety analysis that appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Acknowledgements: Medical writing and editing assistance was provided by Stephanie Rippon, MBio, and Lauren Smith from Complete HealthVizion, funded by the study sponsors. This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Clinical trial information: NCT02677896. [Table: see text]

Comparison of second-line treatments in patients with castration-resistant prostate cancer with PSA relapse after or during docetaxel chemotherapy.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 243-243 ◽  
Author(s):  
David J. K. P. Pfister ◽  
Daniel Porres ◽  
Charlotte Piper ◽  
Axel S. Merseburger ◽  
Theodor Klotz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progressive Disease ◽  
Treatment Options ◽  
Line Treatment ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Grade 3 ◽  
Docetaxel Chemotherapy

243 Background: Docetaxel was the first agent with a proven survival benefit and improved quality of life in patients with castration resistant prostate cancer. Recently there are two new agents, Cabazitaxel (Caba) and Abiraterone Acetate (AA) approved for the second-line treatment in case of progressive disease after Docetaxel. We compared the PSA response and complication rate of these three different second-line treatment options: Caba, AA and Docetaxel Re-Challenge (R-Doc). Methods: The data of 71 patients with progressive disease after/during Docetaxel chemotherapy were analyzed retrospectively. 25 patients with R-Doc, 27 patients with AA and 19 patients with Caba. All patients except two had a PSA-Response or stable disease to primary docetaxel chemotherapy. Mean patient age was 74 years for R-Doc, 71 for AA and 69 for Caba with a mean PSA before initiating treatment of 45 ng/ml, 162ng/ml and 563ng/ml. Results: PSA response rates (>50% regression) were seen in 14 (56%), 8 (38%) and 6 (32%) patients respectively. PSA stabilization was seen in 7 (28%), 2 (9,5%) and 7 (36,8%) patients. Haematologic complications grade >=3 were seen more frequently in R-Doce (32%) and Caba (42%) compared to AA (4%). Cardiovascular complications >= grade 3 were seen in 30% of the patients with AA whereas none of the patients with R-Doc or Caba had cardiovascular grade 3 or 4 side effects. Conclusions: With AA, Caba and the possibility of R-Doc there are compareable treatment options with regard to PSA response rates, even if a stable disease can be seen more frequently in Caba and R-Doc. As the drugs have different side effects the first second line treatment should be considered to the patient’s characteristics and comorbidity in the palliative setting. PSA progression free survival and overall survival data are awaited.

Prognostic value of free testosterone (FT) levels during chemotherapy with carboplatin plus weekly docetaxel in metastatic castration- and docetaxel-resistant prostate cancer (mDRPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5039-5039
Author(s):  
Christoph Reuter ◽  
Michael A. Morgan ◽  
Philipp Ivanyi ◽  
Viktor Grünwald ◽  
Axel S. Merseburger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Detection Limit ◽  
Objective Response ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Testosterone ◽  
Disease Response ◽  
Testosterone Levels ◽  
Weekly Docetaxel ◽  
Chain Cleavage

5039 Background: Carboplatin plus docetaxel (DC) may be effective in mDRPC. Platinum(II)-complexes interfere with steroid biosynthesis lowering testosterone levels by inhibiting the cholesterol side chain cleavage enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase (HSD3B1,2) and 17α hydroxylase/C17,20-lyase (CYP17A1). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Treatment consisted of at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone levels were measured before (n = 77) and during DC chemotherapy (n = 69). Results: Of the 100 pts. treated since February 2005, 96% had bone metastases, 45% had lymph node, 27% liver and 21% lung involvement. At the time of the current analysis, the median follow-up was 13.6 months, 93 pts. had died and 97 had progressive disease. The objective response rate was 36.5% in the 63 pts. with measureable disease. Response of prostate-specific antigen (≥50%) was observed in 50% of patients. Median progression-free survival (PFS) for all patients was 6.9 months (CI 95% 5.5, 8.3) and median OS was 15.4 months (CI 95% 11.5, 19.4). The most common reversible grade 3/4 toxicity was leukopenia/ neutropenia (40/32%). Median free testosterone levels were 0.61 pg/ml before and < 0.18 pg/ml during carboplatin/docetaxel treatment (nadir levels, p < 0.001; detection limit < 0.18 pg/ml). Median serum androgene levels (T+DHT) were 0.1 ng/ml before and below the detection limit of < 0.05 ng/ml during DC treatment. In multivariate analyses, LDH, PSA response, free testosterone nadir levels below the detection limit ( < 0.18 pg/mL) during DC treatment were associated with longer OS (p < 0.05). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important salvage treatment option for DRPC patients.

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