Safety and efficacy of 2-weekly cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 284-284
Author(s):  
Alice Clement-Zhao ◽  
Marie Auvray ◽  
Benjamin Verret ◽  
Yann Alexandre Vano ◽  
Antoine Angelergues ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Weekly Dose ◽  
Weekly Schedule ◽  
Castration Resistant Prostate Cancer ◽  
Full Data ◽  
Safety And Efficacy ◽  
Psa Response ◽  
Grade 3

284 Background: Cabazitaxel (C) administered on a 3-weekly dose schedule has shown a survival benefit in mCRPC patients (pts) pre-treated with docetaxel (D) with concerns about toxicity. We sought to evaluate safety and efficacy of a 2-weekly C schedule. Methods: At the EGP hospital from November 2013 to September 2014, 26 mCRPC pts for whom C was indicated (previously treated with D) received C 16 mg/m² on days 1 and 15 of a 4 weeks-cycle plus daily 10 mg prednisone, until completion of 6 cycles, disease progression, unacceptable toxicity or death. We analyzed safety with toxicity grade ≥ 3 and efficacy, including PSA response, time to biochemical progression (TTBP), radiological progression-free survival (rPFS) and overall survival (OS). Results: 26 pts received C in a 2-weekly schedule; full data are available for 20 pts. Median age was 66.5 years, 34.6% of pts were >70 years; 30.8% had ECOG PS 2; 47.8% had Gleason ≥ 8; 53.8% had lymph node metastases; 96.2% had bone metastases; none had lung or liver metastases. Median D cycles previously received were 6; respectively 80% and 88.4% of pts had received ≥ 2 hormonal manipulations and abiraterone acetate (AA). Median baseline hemoglobin was 12.2 g/dL, median PSA 104.6 ng/mL; 42.9% of pts had ALP ≥ 1.5N, 33.3% had LDH ≥ 1.5N. 4 pts (15%) had grade 1 thrombocytopenia at baseline, 1 (3.8%) had grade 4, reflecting diffuse bone marrow involvement. All pts received G-CSF in primary prophylaxis. Median number of C administration was 7, only 4 pts stopped C because of toxicity (2 for asthenia, 1 for febrile neutroepnia, 1 for thrombocytopenia). Toxicities grade ≥3 were: anemia 33.3%; thrombocytopenia 30%; neutropenia 23.8%; febrile neutropenia 5% (1 pt); no grade ≥3 diarrhea was observed. 45% (9 pts) achieved ≥30% PSA response and 30% (6 pts) ≥50% PSA response. Clinical, biological or radiological response occurred in 50% (10 pts). Median TTBP and rPFS were 3.0 months (2.2-3.6) and 4.2 months (2.8-7.4) respectively. Median OS was not reached at the time of data collection. Conclusions: 2-weekly 16 mg/m² C schedule has a manageable toxicity profile in heavily D and AA pretreated mCRPC pts, and warrants controlled prospective evaluation compared to the standard 3-weekly C schedule.

A hypothesis-generating exploratory analysis of efficacy and safety of abiraterone acetate (AA) in African American (Af Am) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 55-55
Author(s):  
Eleni Efstathiou ◽  
Vasily J. Assikis ◽  
Scott A. North ◽  
John Showel ◽  
Thomas E. Hutson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Profile ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Psa Response ◽  
Grade 3

55 Background: The reported increased prostate cancer lethality in Af Ams has been attributed by some to altered androgen receptor (AR) signaling. We compared toxicity, PSA response, time-to-PSA progression (TTPP), and radiographic progression-free survival (rPFS) in Af Am vs non Af Am pts with CRPC treated with AA + prednisone (P) vs placebo + P. We hypothesized that differences in response to AA may be observed if differences in AR signaling exist in Af Ams. Methods: COU-AA-301 is a randomized double blind study of AA (1000 mg + P 5 mg po BID) vs placebo + P post-docetaxel. Results: TTPP, rPFS, and PSA response rate were higher with AA vs placebo. In Af Am pts, treatment emergent AEs (TEAEs) for AA vs placebo occurred in 96.4% vs 100.0% of pts (50.0% and 66.7%, respectively, grade 3/4); serious TEAEs occurred in 42.9% and 33.3% of pts (28.6% and 26.7%, respectively, grade 3/4). The safety profile of AA appears comparable between the Af Am and overall study populations. Conclusions: Although the small number of Af Am pts in this study precludes formal conclusions regarding efficacy and safety of AA in this pt population, the overall trend suggests these pts experienced clinical benefit from AA with a safety profile comparable to the overall study population. These findings do not appear to support the hypothesis that AR signaling accounts for the increased lethality of prostate cancer seen in Af Ams. Further studies of AA in Af Am pts are planned to understand the potential benefit in this population. Additional efforts are needed to increase participation of Af Am pts in clinical trials. [Table: see text]

Prospective evaluation of low-dose ketoconazole plus hydrocortisone (HC) in chemotherapy-pretreated castration-resistant prostate cancer (CRPC) patients.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 227-227
Author(s):  
Ernest N. Lo ◽  
Laurel A. Beckett ◽  
Chong-xian Pan ◽  
Daniel Robles ◽  
Jennifer Marie Suga ◽  
...  
Keyword(s):  
Stable Disease ◽  
Low Dose ◽  
Response Rate ◽  
Randomized Study ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Published Data ◽  
Castration Resistant Prostate Cancer ◽  
Psa Response ◽  
Grade 3

227 Background: Ketoconazole (keto), a known CYP17 inhibitor, is a traditional systemic treatment for CRPC. However, most of the published data has been in the pre-chemo setting; its efficacy in the post-chemo setting has not been as widely reported. Chemo-naive patients treated with attenuated doses of keto (200-300 mg TID) had prostate specific antigen (PSA) response rate (> 50% decline) ranges from 21%-62% and treatment was well tolerated. We hypothesized that low dose keto would likewise possess efficacy and tolerability in the CRPC post-chemo state. Methods: CRPC patients with ECOG PS 0-3, adequate end organ function, who had received at least one chemo were treated with low-dose keto (200 mg PO TID) and HC (20 mg PO q AM and 10 mg PO q PM) until progression, as defined by either RECIST or PSA rise > 50% from nadir or baseline. Primary endpoint was PSA response rate (> 50% reduction from baseline). A Simon minimax design was used. PSA response of > 25% was to be considered promising for further study (versus null rate of < 5%); 25 patients were required. Secondary endpoints included PSA response > 30%, progression-free survival (PFS), duration of stable disease, and evaluation of adverse events (AE). Results: 29 patients were accrued: median age was 71 (range 55-86) and median pretreatment PSA was 76 ng/mL (range 7-11,420 ng/ml); all had prior docetaxel-based chemotherapy. 28 patients were evaluable for response; all were evaluable for toxicity. PSA response of >50% was seen in 48% of patients and 59% of patients had a PSA response of > 30%. Median PFS was 138 days; median duration of stable disease was 123 days. 12 patients had grade 3 or 4 toxicity on treatment. Of the 17 grade 3 AEs, only 3 were considered ‘probably’ or ‘possibly’ related to treatment, while none of the 2 grade 4 AEs were considered related to treatment. Conclusions: In docetaxel pre-treated CRPC patients, low-dose keto + HC is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response with low-dose keto appears comparable to that of abiraterone in this patient context. A prospective randomized study of available post-chemo options is needed to assess comparative efficacy. Clinical trial information: NCT00895310.

SWOG S0354: A phase II trial of CNTO328, a monoclonal antibody against interleukin-6 (IL-6), in chemotherapy pretreated patients (pts) with castration- resistant prostate cancer (CRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5143-5143
Author(s):  
J. K. Pinski ◽  
B. Goldman ◽  
T. Dorff ◽  
P. Mack ◽  
P. Lara ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Castration Resistant Prostate Cancer ◽  
Plasma Cytokines ◽  
Cancer Cell Survival ◽  
Psa Response ◽  
Pleiotrophic Effects ◽  
Grade 3

5143 Background: IL-6 facilitates cancer cell survival via pleiotrophic effects on proliferation, apoptosis, angiogenesis, differentiation, and chemo-resistance. A multicenter phase II study of CNTO328 in chemo pretreated CRPC pts was conducted. Methods: Eligible pts had one prior chemotherapy, Zubrod performance status 0–2, and adequate end-organ function. Regimen: CNTO328 6 mg/kg IV q2 weeks x 12 cycles. Response assessment was q6 weeks. Primary endpoint was PSA response rate (RR) defined as ≥50% reduction. Accrual was completed in 2 stages, with planned accrual of 20 eligible pts in the first stage and 40 overall. Plasma cytokines were measured by Luminex in 44 pts. Results: Of 62 pts, 54 were eligible; all had received prior taxane therapy. Two (3.7%; 95% CI: 0.5%, 12.8%) had PSA response. Of 47 pts evaluable by RECIST, none had a response and 10 (21%) had stable disease (SD). With median follow-up of 6.6 months, median progression-free survival is 1.6 months (95% CI: 1.6, 1.7). Grade 4 toxicity included 1 case of DIC and 1 CNS ischemia; grade 3 toxicities included elevated AST (1), gastritis/esophagitis (2), thrombocytopenia (2), pain (2), leucopenia (1), and neuropathy (2). Median baseline IL-6 levels were 12.5 pg/mL (IQR: 2.5, 41.5). Pts with levels >12.5 pg/mL had worse 6-month survival vs. < 12.5 pg/mL (53% vs 94%, p = 0.02). Post-cycle 1, IL-6 levels were > 250-fold higher, indicating antibody-target complex formation. 33/39 pts had a decline in C-reactive protein (CRP) plasma levels at 6 weeks. Conclusions: CNTO328 was well-tolerated and resulted in a PSA RR of 3.7% and RECIST SD rate of 21%. Declining CRP levels during treatment reflect biologic activity. Elevated baseline IL-6 levels portend a poor prognosis. Additional translational studies will be presented. Additional study of CNTO328 in combination may be warranted. [Table: see text]

A randomized phase II trial of docetaxel plus carboplatin versus docetaxel in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy: The RECARDO trial.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 166-166 ◽  
Author(s):  
Esther W. Bouman-Wammes ◽  
Linda de Munck ◽  
H Pieter van den Berg ◽  
Aart Beeker ◽  
Carolien H. Smorenburg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Weekly Schedule ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response

166 Background: Docetaxel is the standard first-line chemotherapy for patients with castration resistant prostate carcinoma (CRPC). Docetaxel re-challenge has never been tested in a prospective randomized clinical trial. As some studies supported the addition of carboplatin to docetaxel in this setting, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel monotherapy in docetaxel pre-treated CRPC patients. Methods: Patients with CRPC with a progression-free interval (PFI) of at least 3 months after initial treatment with docetaxel were randomized between docetaxel 75mg/m2 or docetaxel 60mg/m2 plus carboplatin AUC 4, both plus prednisone in a 3-weekly schedule. Treatment was continued until progressive disease, unacceptable toxicity or completion of 10 cycles. The primary endpoint is progression-free survival (PFS) (PSA and/or RECIST). Secondary objectives are overall survival, toxicity, PSA response and quality of life. Results: As a result of insufficient recruitment, the study was discontinued early after inclusion of 75 patients, instead of the targeted 150 patients. The median PFS was comparable between both groups (docetaxel 12.7 months versus combination therapy 11.7 months p = 0.99), and no difference in OS was found (median OS 18.5 months versus 18.9 months, p = 0.88). Rates of PSA response were comparable (response/stable PSA in 42.1%/39.4% of the patients in the monotherapy arm versus 35.1%/48.6% in the combination arm, NS). The incidence of grade 3-4 infections and gastro-intestinal (GI) side effects was higher in the docetaxel plus carboplatin arm (GI side effects 0% versus 13.9% p = 0.03; infection 2.7% versus 16.7% p = 0.056). The difference in febrile neutropenia (0% versus 11.1%) is not significant. Conclusions: For patients with CRPC and an initial good response to docetaxel, re-treatment with docetaxel monotherapy is a feasible, save and effective treatment. Addition of carboplatin resulted in more toxicity. Docetaxel re-challenge is a viable therapeutic option for selected patients. Clinical trial information: NTR3070.

AR changes in circulating-tumor DNA (ctDNA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with high-dose testosterone.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5058-5058 ◽  
Author(s):  
Marcus W. Moses ◽  
Elisa Ledet ◽  
Charlotte Manogue ◽  
Patrick Cotogno ◽  
Brian E. Lewis ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Genomic Alterations ◽  
Start Date ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3 ◽  
Relationship Of

5058 Background: High-dose testosterone (HDT) is active in mCRPC pts and may allow successful re-sensitization to previously utilized androgen-axis targeted therapies. The relationship of genomic alterations in AR gene to HDT responsiveness is unclear. Methods: Analysis of consecutive pts treated with ≥1 dose of HDT (testosterone cypionate q 2-4 weeks n = 29; continuous gel n = 4). Baseline characteristics, ctDNA data (Guardant360), and clinical outcomes were assessed. Presence of genomic AR alterations included amplifications (amps) and mutations (muts); all muts had allele fraction ≥0.3%. PSA response rates included PSA declines of > 30% or ≥50%. PSA-progression-free survival (PSA-PFS) was defined as HDT start date to PSA ≥ 25% over baseline after a second confirmed PSA rise. Results: Between May 2016 and Feb 2018, 33 mCRPC pts had median age 73 (58-85), 39% Gleason 8-10, 100% bone mets, 24% nodes + bone, and median baseline PSA level 36.1 ng/mL (0.04-1290). HDT was given post-median of 2 (1-10) CRPC therapies. 73% (24/33) of pts previously received abiraterone (n = 14), enzalutamide (n = 4), or both sequentially (n = 6) prior to HDT for a median of 10.5 months (0.7-56.8). Baseline ctDNA showed 42% AR alterations (amps = 8, muts = 4, both = 2); 33% TP53, and 6% DNA repair (ATM n = 1; BRCA2 n = 1). With median follow-up 4.4 months, HDT given for median of 4.2 months (95% CI, 3.6-4.8); 29% had PSA ≥50% response and 45% PSA ≥30% response. Median PSA-PFS is immature at 5.5 months (95% CI, 1.5-9.5); 14 pts still on HDT treatment. Grade ≥3 AEs were observed in 6% of pts (G4 thrombocytopenia = 1; G4 asthenia = 1). For pts with baseline AR alterations and HDT treatment, repeated ctDNA assays (n = 7) showed that 100% had decreased AR alterations. No relationship between PSA response and baseline ctDNA AR characteristics are discerned at this time. Conclusions: HDT was safe and active in a subset of mCRPC. Responses were clearly noted for men receiving continuous daily testosterone gels, thus continuously high testosterone levels are active in addition to injection-induced bipolar changes. Further understanding of the genomic alterations predicting responsiveness to HDT in mCRPC is required.

Phase II study of weekly cabazitaxel for "unfit" metastatic castration resistant prostate cancer patients progressing after docetaxel treatment: Preliminary toxicity analysis—SOGUG-CABASEM trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16014-e16014
Author(s):  
Miguel Angel Climent Duran ◽  
Begoña Perez-Valderrama ◽  
Montserrat Domenech ◽  
Begoña Mellado ◽  
Ovidio Fernandez Calvo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Febrile Neutropenia ◽  
Dose Intensity ◽  
Dose Schedule ◽  
Weekly Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Grade 3 ◽  
Daily Prednisone

e16014 Background: Docetaxel (D) is standard first-line chemotherapy in patients (pts) with metastatic castration-resistant prostate cancer (CRPC). Cabazitaxel (C), a novel taxane developed to overcome D resistance, showed an overall survival improvement in second line CRPC in a three-weekly dose schedule. Its main toxicity is hematological with a risk of febrile neutropenia, especially in unfit patients. We aimed to evaluate efficacy and safety of weekly C/prednisone in "unfit" metastatic CRPC previously treated with D. Methods: Unfit pts (ECOG 2, dose reduction due to febrile neutropenia during treatment with D or radiation therapy affecting more than 25% of bone marrow reserve) with advanced CRPC progressing after D treatment with ECOG <=2 and adequate bone marrow, liver and kidney functions were included. C 10 mg/m2 was administered on days 1, 8, 15 and 22 of 5-week cycles with daily prednisone 5 mg b.i.d. Radiological and PSA response was evaluated according to the PCCTWG II criteria and toxicity according NCI-CTC AE. Results: To date 28 pts have been enrolled and data are available for 21. Median age was 74 y (range 60-83), 13 (62%) pts had ECOG 2, 16 (76%) had bone metastases. Sixty-one cycles were administered (median: 3; range: 1-6) and 225 weekly administrations (median 10; range 1-24). Mean dose intensity was 94%. Most frequent related adverse events (AEs) of all grades as % of cycles were: asthenia (40%), anemia (34%), leukopenia (11%), thrombocytopenia (13%), diarrhea (10%), rash (8%), nauseas (8%), dysgeusia (8%), xerostomia (8%), anorexia (7%), mucositis (5%) and neuropathy (3%). Grade 3-4 AEs as % of cycles were: thrombocytopenia (8%), asthenia (7%), mucositis (2%), nausea (2%) and vomiting (2%). One patient discontinued the study due to asthenia G3. No grade III/IV diarrhea, neutropenia or febrile neutropenia were observed. Conclusions: Administration of weekly C (10 mg/m2) to unfit pts seems to be safe with no grade ≥3 neutropenia, diarrhea and febrile neutropenia reported. If confirmed in a larger scale, weekly C may represent an attractive option for unfit pts with mCRPC progressing after D treatment. Clinical trial information: NCT01518283.

Results of a phase II study of sunitinib (SU) maintenance after response to docetaxel in metastatic castration-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 153-153 ◽  
Author(s):  
Bernhard J. Eigl ◽  
Misha Eliasziw ◽  
Scott A. North ◽  
Marc G. Trudeau ◽  
Eric Winquist ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3

153 Background: Docetaxel (D) remains the standard first cytotoxic therapy in mCRPC. Given its mechanism of action, acceptable toxicity profile and simple administration, SU had potential as maintenance therapy for mCRPC. In this multicenter study, we evaluated the tolerability and efficacy of SU monotherapy in patients (pts) with mCRPC who have responded to D. Methods: Pts withmCRPC and responding/stable disease at the time of D completion were enrolled in this multicentre trial. Pts received 50mg of SU daily on 4/2 week on/off cycles. The primary endpoint was progression-free survival (PFS), defined on the basis of RECIST criteria and worsening disease-related symptoms requiring further therapy. Because the effect of SU on PSA is not well known, PSA progression alone was not considered disease progression. PFS of 180 days was considered to be a clinically meaningful threshold for recommending further study of SU. PSA response was a secondary endpoint. The threshold for PSA-progression (PSA-P) was defined as a 25% increase in PSA over baseline. Results: Twenty-three pts were enrolled and treated. Mean age was 66.5 years (48-78). ECOG scores of 0, 1, and 2 were reported for 9, 13 and 1 pts respectively. Mean number of prior cycles of D was 8.6 (4-12). A total of 92 cycles of SU were administered; a mean of 4 per pt (1-11). Mean follow-up was 5.4 months (0.6-15). A total of 479 adverse events (AE) were recorded, of which 88% were Grade 1-2 and 12% were Grade 3-4. The AE were of a type and severity expected for SU. Three Grade 4s occurred, consisting of hepatitis, myelosuppression, and pneumonia. Median PFS was 133 days (95% CI: 48-154). Most pts had immediate PSA increases without evidence of disease progression, with the mean increases in PSA over baseline being 197%, 342%, and 1437% in Cycles 1, 2, and 3, respectively (p<0.05). Conclusions: Although SU was well tolerated as maintenance therapy with predictable side-effects, median PFS was lower than the predefined threshold of 180 days. PSA values were not informative as significant increases were observed as early as Cycle 2. This agent is not considered worthy of further investigation in this setting of maintenance therapy. Clinical trial information: NCT00550810.

Phase II Trial of Consolidation Docetaxel and Samarium-153 in Patients With Bone Metastases From Castration-Resistant Prostate Cancer

2009 ◽  
Vol 27 (15) ◽  
pp. 2429-2435 ◽  
Author(s):  
Karim Fizazi ◽  
Philippe Beuzeboc ◽  
Jean Lumbroso ◽  
Vincent Haddad ◽  
Christophe Massard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Bone Metastases ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Psa Relapse ◽  
Castration Resistant ◽  
Psa Response ◽  
Grade 3

PurposeTo assess docetaxel combined with samarium-153–ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration-resistant prostate cancer (CRPC).Patients and MethodsPatients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m2/wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA–progression-free survival (PFS) as the primary end point.ResultsForty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel–samarium-153–EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%).ConclusionCombining docetaxel and samarium-153–EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms.

A phase II study of patupilone in patients (pts) with metastatic castration- resistant prostate cancer (CRPC) who have progressed after docetaxel

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5139-5139 ◽  
Author(s):  
E. K. Beardsley ◽  
F. Saad ◽  
B. Eigl ◽  
P. Venner ◽  
S. Hotte ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Serious Adverse Events ◽  
Disease Response ◽  
Measurable Disease ◽  
Psa Response ◽  
Grade 3 ◽  
Ecog Ps

5139 Background: Chemotherapy for pts with CRPC who have progressed after docetaxel remains to be defined. Patupilone is an epothilone with broad spectrum pre-clinical activity including in taxane resistant models. Methods: Multicenter, 2-stage design. Pts with metastatic CRPC with progressive disease during or within 6 months of receiving docetaxel were eligible. Patupilone was initially given 10mg/m 2 IV every 3 weeks. PSA response rate (≥50% decline) was the primary endpoint (H0 = 15%, H1 = 25%, α = 0.1, β = 0.2). Secondary endpoints were measurable disease response, serial pain and analgesics scores, progression free survival (PFS) and overall survival (OS). Results: 83 pts were enrolled from March 2007-June 2008. 401 cycles administered (median 5, range 1–15). Baseline characteristics (range): median age 67 (47–85), PSA 212 (2.6–11520), hemoglobin 118 (89–160), median time to progression after docetaxel 1.0 months (0.0–6.0), number of prior chemotherapy regimens 1:2:3+ in 45:28:10 pts, ECOG PS 0–1:2 in 73:10 pts, disease in bone/lymph nodes/viscera in 76/47/14 pts respectively. In the first 6 pts, gastrointestinal serious adverse events (AE) occurred in 4 pts (diarrhea and vomiting) which lead to a dose reduction of patupilone to 8 mg/m2 for subsequent patients. Grade 3/4 related adverse events at this dose included fatigue (16%), diarrhea (13%) and anorexia (5%). There were no grade 3/4 hematologic AEs. In 78 pts evaluable for PSA response, PSA declines of ≥30% and ≥50% have occurred in 44/78 (56%) and 35/78 (45%) with a confirmed PSA response in 25 pts (32%). Partial response occurred in 5% and stable disease in 64% of 44 evaluable pts. Pain response (2 point decline on 6 point scale) occurred in 36 (51%) of 71 pts eligible for analysis. Median PFS for PSA and non-PSA outcomes (measurable disease/symptomatic progression or death) was 7.6 months (3.7–11.5) and 5.6 months (3.9–7.3) respectively. Follow up for OS is continuing. Conclusions: Patupilone 8 mg/m2 every 3 weeks was well tolerated and associated with encouraging PFS, PSA and pain responses in pts with docetaxel resistant/refractory disease. Further investigation of patupilone in this population is warranted. [Table: see text]

Phase II study of weekly cabazitaxel for "unfit" metastatic castration resistant prostate cancer patients progressing after docetaxel treatment: Preliminary toxicity analysis (SOGUG-CABASEM trial).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 190-190
Author(s):  
Miguel Angel Climent Duran ◽  
Begoña Perez-Valderrama ◽  
Eva Fernandez Parra ◽  
Begoña Mellado ◽  
Montserrat Domenech ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Febrile Neutropenia ◽  
Specific Antigen ◽  
Dose Intensity ◽  
Dose Schedule ◽  
Weekly Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Grade 3

190 Background: Docetaxel (D) is standard first-line chemotherapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Cabazitaxel (C), a novel taxane developed to overcome D resistance, showed an overall survival improvement in second line CRPC in a three-weekly dose schedule. Its main toxicity is hematological, especially in unfit patients. We aimed to evaluate efficacy and safety of weekly C/pred. in "unfit" mCRPC previously treated with D. Methods: Unfit pts (ECOG 2, dose reduction due to febrile neutropenia during treatment with D or radiation therapy affecting more than 25% of bone marrow reserve) with advanced CRPC progressing after D treatment with ECOG <=2 and adequate bone marrow, liver and kidney functions were included. C 10 mg/m2 was administered on days 1, 8, 15, and 22 of 5-week cycles with daily pred. 5 mg b.i.d. Radiological and prostate-specific antigen response was evaluated according to the PCCTWG II criteria and toxicity according NCI-CTC AE. Results: To date 47 pts have been enrolled and data are available for 38. Median age was 72 (range 56 to 83), 20 (53%) pts had ECOG 2, 29 (83%) had bone metastases. Cycles administered: 124 (median: 3; range: 1 to 9) and 446 weekly administrations (median 11; range 1 to 35). Mean dose intensity was 94%. Most frequent toxicities of all grades as % of cycles were: asthenia (20%), anemia (50%), leukopenia (13%), thrombocytopenia (14%), diarrhea (9%), rash (6%), nauseas (5%), dysgeusia (7%), xerostomia (6%), anorexia (5%), hand-foot syndrome (5%), and neuropathy (2%). Grade 3: thrombocytopenia (10%), anemia (6%), neutropenia (1%), asthenia (3%), anorexia (1%), mucositis (1%), nausea (1%), and vomiting (1%). No grade 4 toxicities were reported. Three patients discontinued the study due to asthenia G3 (2) and mucositis G3 (1). No grade III/IV diarrhea or febrile neutropenia were observed. Conclusions: Administration of weekly C (10 mg/m2) to unfit pts seems to be safe with no grade 3 or greater neutropenia, diarrhea, or febrile neutropenia reported. If activity is confirmed, weekly C may represent an attractive option for unfit pts with mCRPC progressing after D treatment. Clinical trial information: NCT01518283.

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