Prediction of survival benefit from docetaxel chemotherapy with PSA response and PSA half-life in men with metastatic hormone refractory prostate cancer

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 16126-16126
Author(s):  
S. A. North ◽  
M. Hanninen ◽  
P. M. Venner
Keyword(s):  
Prostate Cancer ◽  
Half Life ◽  
Survival Benefit ◽  
Hormone Refractory Prostate Cancer ◽  
Prediction Of Survival ◽  
Psa Response ◽  
Hormone Refractory ◽  
Docetaxel Chemotherapy

scholarly journals A rapid PSA half-life following docetaxel chemotherapy is associated with improved survival in hormone refractory prostate cancer

2013 ◽  
Vol 3 (5) ◽  
pp. 369 ◽  
Author(s):  
Mikael Hanninen ◽  
Peter Venner ◽  
Scott North
Keyword(s):  
Prostate Cancer ◽  
Half Life ◽  
Specific Antigen ◽  
Rapid Rate ◽  
Chi Square ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Psa Response ◽  
Hormone Refractory ◽  
Docetaxel Chemotherapy

Introduction: Docetaxel chemotherapy prolongs survival in metastatichormone-refractory prostate cancer (mHRPC), but many patientsfail to respond to this therapy and there is potential for serioustoxicity. Patients differ in their percent prostate-specific antigen(PSA) decline and rate of PSA decline following treatment. Wepropose that patients who achieve a rapid rate of PSA decline,measured as a shorter PSA half-life (PSAHL), may experience alonger overall survival (OS) than those who achieve a slower rateof PSA decline.Methods: A chart review of patients treated with docetaxel formHRPC in Alberta from January 2000 to May 2006 was performed.At 42 days (after 2 cycles) and 84 days (after 4 cycles) followingchemotherapy, PSA response and PSAHL were determined. PSAHLcould only be determined in patients with a PSA drop from baseline.Optimal PSAHL values for OS stratification were determinedusing the log-rank chi-square statistic. Survival analysis was carriedout using Kaplan-Meier curves and regression analysis.Results: There were 154 patients who fulfilled the inclusion criteria.Using 42-day postdocetaxel data, no associations with OScould be demonstrated. Using 84-day postdocetaxel data, patientsstratified by PSAHL demonstrated a significant difference in OS(15 months vs. 25 months) and this relationship remained followingmultivariate analysis (hazard ratio 0.08 [0.021-0.34]).Conclusion: A more rapid rate of PSA decline (PSAHL <70 days)measured after 4 cycles of chemotherapy was associated with alonger OS. This result was independent of other known markersof survival and allowed for a greater survival differentiation thanPSA response.Introduction : La chimiothérapie par docetaxel prolonge la surviedans les cas de cancer métastatique de la prostate réfractaire auxtraitements hormonaux, mais de nombreux patients ne répondentpas à cette chimiothérapie qui, par ailleurs, est associée à un risquede toxicité grave. Après ce traitement, le pourcentage de baissedu taux d’antigène prostatique spécifique (APS) et la vitesse deréduction des taux d’APS diffèrent d’un patient à l’autre. Nousavançons l’hypothèse que les patients qui présentent une baisserapide des taux d’APS, se manifestant par une réduction de la demiviede l’APS, peuvent présenter une survie globale (SG) plus longueque les patients présentant une baisse plus lente des taux d’APS.Méthodologie : Nous avons procédé à un examen des dossiers depatients traités par le docetaxel en raison d’un cancer métastatiquede la prostate réfractaire aux traitements hormonaux en Albertaentre janvier 2000 et mai 2006. Aux 42e (après 2 cycles) et 84ejours (après 4 cycles) de chimiothérapie, on a vérifié la réponseen fonction des taux d’APS et de la demi-vie de l’APS. La demiviede l’APS ne pouvait être mesurée que chez les patients ayantaffiché une baisse des taux d’APS par rapport aux taux initiaux.Les valeurs optimales de la demi-vie de l’APS utilisées pour lastratification des patients en vue de l’évaluation de la SG ont étécernées à l’aide d’une méthode statistique reposant sur le test deMantel-Haenzel. L’analyse des taux de survie a été effectuée àl’aide de courbes de Kaplan-Meier et d’une analyse de régression.Résultats : Cent cinquante-quatre (154) patients satisfaisaient auxcritères d’inclusion. Selon les données recueillies après 42 joursde traitement par docetaxel, aucune corrélation avec la SG n’apu être démontrée. Selon les données recueillies après 84 joursde traitement par docetaxel, les patients stratifiés en fonction deleur demi-vie de l’APS ont montré une différence significativequant à la survie globale (15 mois vs 25 mois), et cette corrélationa aussi été observée lors de l’analyse multivariée (RR 0,08[0,021 à 0,34]).Conclusion : Une chute plus rapide des taux d’APS (demi-vie del’APS < 70 jours) mesurée après 4 cycles de chimiothérapie a étéassociée à une survie globale plus longue. Ce résultat s’est révéléindépendant des autres marqueurs connus de la survie et permet -tait une meilleure différenciation que la réponse de l’APS sur leplan de la survie.

PSA Kinetics Provide Improved Prediction of Survival in Metastatic Hormone-Refractory Prostate Cancer

Urology ◽  
2008 ◽  
Vol 72 (4) ◽  
pp. 903-907 ◽  
Author(s):  
David Robinson ◽  
Gabriel Sandblom ◽  
Robert Johansson ◽  
Hans Garmo ◽  
Gunnar Aus ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormone Refractory Prostate Cancer ◽  
Psa Kinetics ◽  
Prediction Of Survival ◽  
Hormone Refractory

Phase 1 study of atrasentan (ABT627), novel endothelin receptor-A antagonist, in Japanese patients with hormone refractory prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14602-14602
Author(s):  
Y. Fujisaka ◽  
Y. Fujiwara ◽  
K. Yamada ◽  
T. Shimizu ◽  
A. Horiike ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Half Life ◽  
Phase 1 ◽  
Plasma Concentrations ◽  
Study Drug ◽  
Japanese Patients ◽  
Maximum Plasma ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

14602 Background: Endothelin (ET)-1 and its primary receptor, the ETA receptor, contribute to tumor cell growth, survival, angiogenesis and invasion. Atrasentan is a highly potent, selective ETA receptor antagonist. This study assessed safety and pharmacokinetics (PK) in Japanese patients with hormone refractory prostate cancer. Methods: This open-label, single-center Phase I trial evaluated the safety and PK of escalating oral atrasentan doses (2.5, 10 or 20 mg) given daily on day 1 and day 4 through 27 (except day 2 and 3). Dose-limiting toxicity (DLT) was defined as Grade 3 or greater adverse events related to study drug. Results: Eighteen patients, aged 54–74 (median; 66) were treated in cohorts of 6 patients each. The compliance of all patients was 100%. The most common toxicities were rhinitis, peripheral edema, headache, hypotension and anemia, all of which were well tolerated. These events were consistent with the anticipated vasodilatory effects or with a hemodilution effect of the study drug. DLTs were not observed. Atrasentan was rapidly absorbed following oral administration of 2.5 to 20 mg, maximum plasma concentrations averaged from 0.4 to 0.8 hours. After peaking, plasma concentrations declined bi-exponentially with a terminal half-life of approximately 25 hours. In the 10 mg dosing group, the steady-state maximum plasma concentration (Cmax) and the area under the curve (AUC0–24h) averaged 135.5 ng/mL and 533 ng h/mL, respectively. The Cmax and AUC values generally increased linearly with increasing dose after single- and multiple-dose administration. Compared to baseline, PSA decreased 50% or more in 1 patient (20 mg) and increased 25% or more in 10 patients (2.5 mg;2, 10 mg;5, 20 mg;3). The PSA of the remaining 7 patients (2.5 mg;4, 10 mg;1, 20 mg;2) ranged from < 25% increase to < 50% decrease. Fourteen patients continued on study drug in an extension study. Conclusions: Atrasentan is well tolerated, with no dose-limiting adverse events observed up to 20 mg in Japanese patients. The main adverse events are consistent with the vasodilatory effect of the drug. PK are linear and dose-proportional; the half-life is appropriate for once-daily dosing. No significant financial relationships to disclose.

PSA flare-up in patients with hormone-refractory prostate cancer (HRPCA) receiving docetaxel-based chemotherapy: Incidence and differentiation from progressive disease

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14523-14523
Author(s):  
D. Sahi ◽  
C. H. Ohlmann ◽  
I. Cordia ◽  
U. Engelmann ◽  
A. Heidenreich
Keyword(s):  
Prostate Cancer ◽  
Progressive Disease ◽  
Initial Increase ◽  
Hormone Refractory Prostate Cancer ◽  
Common Phenomenon ◽  
Maximum Increase ◽  
Psa Response ◽  
Hormone Refractory ◽  
Initiation Of Therapy ◽  
Doubling Times

14523 Background: Docetaxel-based chemotherapy displays the standard therapy for patients with hormone-refractory prostate cancer. A subset of patients will experience an initial PSA increase after initiation of therapy followed by a subsequent PSA decrease. The aim of our study was to investigate the incidence of this phenomenon and to identify factors that differentiate the flare-up from progressive disease. Methods: We retrospectively analyzed the patient records of 46 patients who received docetaxel as monotherapy or in combination with either mitoxantron or estramustine for hormone-refractory prostate cancer. PSA flare-up was defined as an initial PSA increase of more than 25% after initiation of therapy over baseline followed by a PSA decrease of at least 75% compared to the maximum increase over baseline. Progressive disease was defined as a PSA increase of at least 25% over baseline in patients with no PSA response which had to be confirmed four weeks later. Results: Of 46 patients who received docetaxel-based chemotherapy 16 (34.8%) showed a PSA decrease of at least 50%, 6 (13.0%) between 30–50%, 17 (37.0%) had stable disease and 7 (15.2%) patients experienced progressive disease. An initial PSA increase followed by a subsequent PSA decrease was seen in 6 (13.0%) of the patients. Median PSA increase compared to baseline was 81.0% (25–239). The median following PSA decrease was 110.5% (77–160) compared to the initial increase. Median PSA doubling times of patients with PSA flare up or progressive disease were 113.3 and 100.7 days (p = 0.7941), respectively. Conclusions: PSA flare-up seems to be a common phenomenon in patients being treated with docetaxel-based chemotherapy for hormone-refractory prostate cancer. In order not to prevent those patients from a subsequent PSA decrease by early cessation of therapy it would be useful to discriminate them from patients with progressive disease. According to the results of our study PSADT does not differ between patients with flare-up or progressive disease and can therefore not be used to distinguish between the two. No significant financial relationships to disclose.

Induction of complete remission in metastatic hormone-refractory prostate cancer: A combined anti-inflammatory therapy approach

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15636-15636 ◽  
Author(s):  
A. Reichle ◽  
B. Walter ◽  
A. Berand ◽  
M. Vogelhuber ◽  
K. Bross ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Complete Remission ◽  
Objective Response ◽  
Hormone Refractory Prostate Cancer ◽  
Who Grade ◽  
Therapy Approach ◽  
Psa Response ◽  
Anti Inflammatory ◽  
Hormone Refractory ◽  
Negative Predictor

15636 Background: The present multi-centre phase II study was designed to support the hypothesis that networking agents binding to ubiquitous accessible targets in metastatic hormone-refractory prostate cancer (HRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating objective response (primary endpoint). Method: Patients with metastatic HRPC, received both an anti- inflammatory and angiostatic therapy consisting of low-dose chemotherapy with capecitabine 1 g twice daily for 14 days every 3 weeks, day 15+, COX-2 blockade with etoricoxib 60 mg daily, day 1+, combined with two transcription modulators, pioglitazone 60 mg daily, day 1+, plus dexamethason 1 mg daily for 14 days, every 3 weeks, day 15+, until disease progression. The study was planned using the Simon optimal design. Results: Thirty-six consecutive patients (N= 22 (61%) chemo-naive, n= 14 (39%) with preceding chemotherapies, mean 2.1 regimen) with metastatic HRPC, confirmed PSA increase, assessable response, and ECOG 0–2 were enrolled between 1/03 to 5/06. Objective response occurred in 10 of 13 cases (N/n: 41%/7%) with PSA (and C-reactive protein) response >50% (N/n: 45%/21%). Median time to PSA response was 2.4 months (range 1.0 to 7.3 months). Two of three patients responding with PSA <4 ng/ml achieved complete remission after 9 and 16 months, 16 patients stable disease (N/n: 41%/64%), and 5 patients experienced progressive disease (N/n: 14%/14%). Median progression-free survival (PFS) was 3.6 months (range 0.5 to 28.5) and median overall survival (OS) 14.4 months (range 0.6 to 37.2). Multivariate analysis recognized pre-treatment with chemotherapy as negative predictor for both OS (hazard ratio 2.26 (CI 95%: 0.970; 5.277), p=0.05) and PFS (HR 2.47 (CI 95%: 1.146; 5.348), p= 0.02), and <50% PSA response as negative predictor for PFS (HR 0.38 (CI 95%: 0.171; 0.857), p= 0.01). Toxicities > WHO grade II were reported: Hand-foot syndrome (n=1), anemia (n=6), edema (n=1), cushing syndrome (n=1), hydronephrosis (n=1). Conclusions: This is the first study reporting continuous complete remissions in HRPC with a biomodulatory therapy approach. Further, the study may clinically support the upper mentioned hypothesis. No significant financial relationships to disclose.

scholarly journals SCLERODERMA-LIKE SKIN SCLEROSIS INDUCED BY DOCETAXEL CHEMOTHERAPY FOR HORMONE REFRACTORY PROSTATE CANCER: A CASE REPORT

2010 ◽  
Vol 101 (6) ◽  
pp. 726-729
Author(s):  
Takeshi Maehana ◽  
Takahiro Mizuno ◽  
Masatoshi Muto ◽  
Naotaka Nishiyama ◽  
Masahiro Yanase
Keyword(s):  
Prostate Cancer ◽  
Case Report ◽  
Hormone Refractory Prostate Cancer ◽  
Skin Sclerosis ◽  
Hormone Refractory ◽  
Docetaxel Chemotherapy

Identification of candidate biomarkers of therapeutic response to docetaxel in hormone-refractory prostate cancer by proteomic profiling

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11010-11010
Author(s):  
L. Horvath ◽  
L. Zhao ◽  
B. Lee ◽  
D. Brown ◽  
M. Molloy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Plasma Levels ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Protein Profiling ◽  
Hormone Refractory Prostate Cancer ◽  
Psa Response ◽  
Pc3 Cells ◽  
Hormone Refractory

11010 Background: Docetaxel (DTX)-based chemotherapy improves symptoms and survival in men with advanced hormone-refractory prostate cancer (HRPC). However, approximately 50% of patients do not respond to DTX but are exposed to significant toxicity without direct benefit. This study aimed to identify novel therapeutic targets and predictive biomarkers of DTX-resistance in HRPC. Methods: Protein profiling using iTRAQ mass spectrometry compared the PC3-Rx and DTX-sensitive PC3 cells and DTX-resistant PC3-Rx developed by DTX dose-escalation. Functional validation experiments were performed using recombinant protein treatment and siRNA knockdown experiments. Plasma/serum samples were collected from 41 men with metastatic HRPC treated with DTX-based chemotherapy (36 with paired samples pre- and post- cycle 1 DTX). Serum/plasma levels of MIC-1 were measured by ELISA. The association between MIC-1 levels, PSA response and overall survival (OS) were assessed by non-parametric tests and Kaplan-Meier survival analysis. Results: The IC50 for DTX in PC3-Rx was 10-fold higher than that in parent PC-3 cells. Protein profiling identified that MIC-1 levels were elevated 2.4 fold and AGR2 decreased 2.4 fold in DTX resistant cells. Knockdown of AGR2 expression in PC3 cells resulted in increased DTX resistance (p=0.03). PC-3 cells treated with recombinant MIC-1 also became resistant to DTX (p=0.001). Conversely, treating PC3-Rx cells with MIC1-siRNA restored sensitivity to DTX (p=0.002). In HRPC patients, pre-treatment MIC-1 levels did not correlate with PSA response to treatment (p=0.6). In contrast, increased serum/plasma levels of MIC-1 after cycle one of chemotherapy were associated with DTX resistance (p=0.006) and shorter overall survival (p=0.002). Conclusions: These results suggest that both AGR2 and MIC-1 play a role in DTX resistance in HRPC. Furthermore, changes in serum/plasma MIC-1 levels are associated with DTX resistance in a correlative human cohort. While a larger study is needed to validate these findings, the data provide evidence that MIC-1 as a potential predictive biomarker and both MIC-1 and AGR2 are potential therapeutic targets in DTX resistance. No significant financial relationships to disclose.

673 DOCETAXEL - RECHALLENGE AT PSA RELAPSE AFTER DOCETAXEL CHEMOTHERAPY AT HORMONE REFRACTORY PROSTATE CANCER

2010 ◽  
Vol 183 (4S) ◽  
Author(s):  
Peter Firek ◽  
David Pfister ◽  
David Thüer ◽  
Bernhard Brehmer ◽  
Robin Epplen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormone Refractory Prostate Cancer ◽  
Psa Relapse ◽  
Hormone Refractory ◽  
Docetaxel Chemotherapy

Ixabepilone (Epothilone B Analogue BMS-247550) Is Active in Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer: A Southwest Oncology Group Trial S0111

2005 ◽  
Vol 23 (34) ◽  
pp. 8724-8729 ◽  
Author(s):  
Maha Hussain ◽  
Catherine M. Tangen ◽  
Primo N. Lara ◽  
Ulka N. Vaishampayan ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Hormone Refractory Prostate Cancer ◽  
Grade 5 ◽  
Psa Response ◽  
Hormone Refractory ◽  
Grade 3

Purpose The epothilones are a new class of tubulin-polymerizing agents with activity in taxane-sensitive and resistant tumor models. We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HRPC). Methods Eligible patients had chemotherapy-naive metastatic HRPC, a Zubrod performance status of 0 to 2, and adequate organ function. All patients received BMS-247550 at 40 mg/m2 over 3 hours every 3 weeks. The primary end point was proportion of patients achieving a prostate-specific antigen (PSA) response. Results Forty-eight patients with metastatic HRPC were registered. Forty-two patients were eligible, with a median age of 73 years and a median PSA level of 111 ng/mL; 78% had bone-only or bone and soft tissue metastases, and 88% had objective radiologic disease progression at registration. Grade 3 and 4 adverse events (AEs) occurred in 16 and three patients, respectively. All grade 4 toxicities were neutropenia or leukopenia. The most frequent grade 3 AEs were neuropathy (eight patients), hematologic toxicity (seven patients), flu-like symptoms, and infection (five patients each). There were no grade 3/4 thrombocytopenia or grade 5 AEs. There were 14 confirmed PSA responses (33%; 95% CI, 20% to 50%); 72% of PSA responders had declines greater than 80%, and two patients achieved an undetectable PSA. The estimated median progression-free survival is 6 months (95% CI, 4 to 8 months), and the median survival is 18 months (95% CI, 13 to 24 months). Conclusion Ixabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted.

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