Randomized phase II trial of docetaxel, with or without doxercalciferol, in advanced, androgen-independent prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5119-5119
Author(s):  
S. Attia ◽  
J. Eickhoff ◽  
G. Wilding ◽  
J. Blank ◽  
H. Rezazadeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Double Blind ◽  
Vitamin D Analogs ◽  
Psa Response ◽  
Androgen Independent

5119 Background: Docetaxel is the standard of care for advanced androgen-independent prostate cancer (AIPC). Doxercalciferol, a vitamin D analog (1a-hydroxyvitamin D2), has single-agent activity in AIPC (Clin Cancer Res 9(11), 2003). Preclinical evidence supports combining vitamin D with chemotherapy to treat AIPC. Here we report results of a multi-institutional trial combining docetaxel and doxercalciferol. Methods: Patients with chemo-naive AIPC were randomized 1:1 to receive, on a four week cycle, docetaxel (35 mg/m2 IV; days 1, 8 and 15) with either doxercalciferol (10 mcg PO daily, days 1–28) or placebo in a double-blind fashion. The primary endpoint was to compare progression-free survival (PFS). Secondary endpoints were to assess overall survival (OS), objective response (RECIST), PSA response (consensus criteria), and toxicity. PFS and OS were analyzed on an intent-to-treat basis. Eligibility criteria included no prior cytotoxic therapy; radiographic evidence of metastasis; performance status ≤ 2 and no recent history of nephrolithiasis. Results: Seventy patients were randomized. Median follow-up time was 16.2 months (range, 0–40.5 months). Median PFS in the doxercalciferol arm was 14.9 months (95% CI: 8.7–16.6 months) versus 11.9 months (95% CI: 8.9–16.4 months) in the placebo arm (p=0.73). Median OS in the doxercalciferol arm was 18.1 months (95% CI: 14.9–26.2 months) and 17.9 months (95% CI: 12.1–24.6 months) in the placebo arm (p=0.63). Twenty-nine patients in the doxercalciferol arm and 33 in the placebo arm were evaluable for objective response. No complete responses were seen. Partial response rate was 14% (doxercalciferol) vs. 15% (placebo) (p=0.88). PSA response rate was 44% (95% CI: 29%-60%) in the doxercalciferol arm and 42% (95% CI: 27%-59%) in the placebo arm (p=0.87). Grade 3/4 toxicity rates were 38% in the doxercalciferol arm and 39% in the placebo arm (p=0.99). Conclusions: Despite encouraging data with other vitamin D analogs combined with docetaxel in AIPC, the addition of daily doxercalciferol to weekly docetaxel did not enhance median PFS, OS or tumor response. Toxicity was similar between treatment groups. Further evaluation of vitamin D analogs in combination with chemotherapy in AIPC remains of interest. No significant financial relationships to disclose.

Phase I study of picoplatin and docetaxel (D) with prednisone (P) in patients (pts) with chemotherapy-naive metastatic hormone refractory prostate cancer (HRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15546-15546
Author(s):  
L. Roman ◽  
P. Karlov ◽  
A. Kaprin ◽  
O. Gladkov ◽  
H. Breitz
Keyword(s):  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Maximum Tolerated Dose ◽  
Platinum Resistance ◽  
Ecog Performance Status ◽  
Psa Response ◽  
Hormone Refractory ◽  
Clinically Significant

15546 Background: Picoplatin is a sterically hindered platinum analogue specifically developed to overcome platinum resistance and to improve on the safety and efficacy of other platinum-based drugs. In >600 pts, picoplatin had single-agent activity in prostate, lung, ovarian and other malignancies with rare clinically significant nephro-, oto-, or neurotoxicity (∼2% grade 3 and 0% grade 4), even in platinum pretreated pts. An objective response rate of 20% and a PSA response rate of 25% were observed following 120 mg/m2 picoplatin q 3 wk in 20 chemotherapy-naïve pts with HRPC. D + P leads to superior survival, increased PSA response and improved quality of life in HRPC pts. Picoplatin has demonstrated synergy with taxanes in pre-clinical studies. Thus the current study is designed to investigate D + P + picoplatin in chemotherapy-naïve pts with metastatic HRPC. Methods: Pts with documented progression of metastatic disease during adequate hormonal therapy, ECOG performance status of 0 or 1 and preserved organ function received D, 60 mg/m2 q 3 wks + P, 5 mg, po bid + picoplatin. Picoplatin has been given to date to sequential cohorts of subjects at 60 mg/m2, 80 mg/m2 and 100 mg/m2. Results: 16 pts have been enrolled and have received up to 8 cycles of therapy. Therapy has been well tolerated. No dose limiting toxicity has been observed. Dose reduction for thrombocytopenia has been required in 1 pt, but there has been no cumulative myelotoxity. 7 pts in the first 3 dose cohorts have been evaluated for efficacy after 4 cycles (12 weeks): at doses below the maximum tolerated dose, there were 3 PSA responses and 1 objective partial response. Dose escalation continues. Conclusion: Picoplatin can be safely administered with D + P in chemo-naïve pts with HRPC. A phase 2 study of this combination will begin when an optimal, safe dose is defined. No significant financial relationships to disclose.

Phase I Trial of Docetaxel With Estramustine in Androgen-Independent Prostate Cancer

1999 ◽  
Vol 17 (3) ◽  
pp. 958-958 ◽  
Author(s):  
Daniel P. Petrylak ◽  
Robert B. Macarthur ◽  
John O'Connor ◽  
Gary Shelton ◽  
Timothy Judge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Response Rate ◽  
Area Under The Curve ◽  
Narcotic Analgesics ◽  
Pain Medications ◽  
Psa Response ◽  
Grade 3 ◽  
Recommended Phase Ii Dose ◽  
Androgen Independent

PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a ≥ 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.

A phase Ib/II trial of indomethacin and enzalutamide to treat castration-resistant prostate cancer (CRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS394-TPS394 ◽  
Author(s):  
Chong-xian Pan ◽  
Primo Lara ◽  
Christopher P. Evans ◽  
Mamta Parikh ◽  
Ralph de Vere White ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Phase Ib ◽  
Androgen Synthesis ◽  
Psa Response

TPS394 Background: Enzalutamide (Enza) and abiraterone (Abi) are commonly used to treat CRPC. Resistance is the most common cause of treatment failure. We discovered that a critical steroidogenic enzyme AKR1C3 was significantly elevated and contributed to intratumoral androgen synthesis in Enza-resistant prostate cancer cells and tumors. Overexpression of AKR1C3 induced androgen receptor variant 7 (AR-V7) expression, while inhibition of AKR1C3 downregulated AR-V7. We then discovered that indomethacin (Indo) inhibited AKR1C3 activation and sensitized resistant CRPC cells to Enza and Abi. One patient accidentally took Indo and achieved biochemical as well as radiological response of his prostate cancer. These findings prompted us to design a clinical trial to test the combination of Indo with Enza for the treatment of CRPC and to study the underlying mechanisms of action and resistance. Methods: This investigator-initiated single-arm Phase Ib/II trial enrolls patients with progressive CRPC after Abi, adequate vital organ function, ECOG performance status 0-2, and serum testosterone < 50 ng/dl. Major exclusion criteria include prior Enza treatment, brain metastasis and history of seizure. In the Phase Ib cohort, patients receive Enza 160 mg po qd and Indo 50 mg po tid to determine toxicity. The Phase II expansion will enroll 26 patients with 21 evaluable patients. This sample size provides 90% power to detect, at the 0.05 level (1-sided), the difference between a PSA response rate of 50% expected with the study treatment and a historical control of 20% with Enza alone. Co-primary endpoints are safety and PSA response of ≥50% decrease. Secondary endpoints include overall response rate as determined by the Prostate Cancer Working Group 2 criteria (PCWG2), progression-free survival and overall survival. Molecular correlative studies are exploratory endpoints. Serum and intratumoral androgen levels, full-length AR, AR-V7 and AKR1C3 will be measured to assess the effect of the combination therapy. To date, 4 patients have been enrolled to the trial (clinicaltrials.gov Identifier No: NCT02935205; this trial is funded by DoD Prostate Cancer Research Program IMPACT award). Clinical trial information: NCT02935205.

KEYNOTE-811 pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction cancer (mG/GEJC): A double-blind, randomized, placebo-controlled phase 3 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4146-TPS4146 ◽  
Author(s):  
Yelena Yuriy Janjigian ◽  
Yung-Jue Bang ◽  
Charles S. Fuchs ◽  
Shukui Qin ◽  
Taroh Satoh ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Response Rate ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Phase 3 ◽  
Double Blind ◽  
End Points ◽  
Flat Dose

TPS4146 Background: Combination therapy with the anti-HER2 antibody trastuzumab with fluoropyrimidine and platinum is the current standard for patients with HER2+ mG/GEJc. We hypothesize that combination anti–PD-1 and anti-HER2 therapy will result in T-cell activation, augment ADCC, and potentiate antitumor immune response in HER2+ patients. This phase 2 study in HER2+ mG/GEJc demonstrated the safety and preliminary efficacy of trastuzumab/pembrolizumab/chemotherapy; the overall response rate was 87%, and the disease control rate was 100% Janjigian YY, ASCO GI 2019). KEYNOTE 811, a global, multicenter, randomized, placebo-controlled, phase 3 study, is underway. Methods: Key eligibility criteria are age ≥18 years; previously untreated unresectable or metastatic HER2+ (centrally confirmed IHC 3+ or IHC 2+/ISH >2.0) G/GEJ adenocarcinoma; life expectancy >6 months with RECIST v1.1 measurable disease; adequate organ function and performance status. Patients will be randomly assigned 1:1 to receive chemotherapy with pembrolizumab 200 mg IV flat dose or placebo with trastuzumab 6 mg/kg (after 8 mg/kg load) Q3W up to 2 years or until intolerable toxicity or disease progression. Investigator choice chemotherapy will include day 1 cisplatin 80 mg/m2 IV and /5-fluorouracil 800 mg/m2/day IV (days 1-5) or oxaliplatin 130 mg/m2 IV and capecitabine 1000 mg/m2 BID days 1-14 (Q3W). Primary end points are progression-free survival and overall survival. Secondary end points are objective response rate, duration of response, and safety and tolerability. Adverse events are graded per NCI CTCAE v4.0 and will be monitored for 30 or 90 days after treatment. Patients will be followed up for survival. Planned enrollment is approximately 692 patients. Clinical trial information: NCT03615326.

KEYNOTE-811 pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction cancer (mG/GEJc): A double-blind, randomized, placebo-controlled phase III study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS463-TPS463
Author(s):  
Hyun Cheol Chung ◽  
Yung-Jue Bang ◽  
Charles S. Fuchs ◽  
Shukui Qin ◽  
Taroh Satoh ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Objective Response Rate ◽  
Cell Activation ◽  
Response Rate ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Phase Iii ◽  
Double Blind ◽  
End Points

TPS463 Background: Combination therapy with the anti-HER2 antibody trastuzumab plus fluoropyrimidine and platinum is the current standard of care for patients with HER2+ mG/GEJc. We hypothesize that combination anti–PD-1 and anti-HER2 therapy will result in T-cell activation, augment antibody-dependent, cell-mediated cytotoxicity, and potentiate antitumor immune response in HER2+ patients. A phase 2 study in HER2+ mG/GEJc demonstrated the safety and preliminary efficacy of trastuzumab/pembrolizumab/chemotherapy; the objective response rate was 87%, and the disease control rate was 100% (Janjigian YY, ASCO GI 2019). KEYNOTE-811 (ClinicalTrials.gov, NCT03615326), a global, multicenter, randomized, placebo-controlled, phase 3 study, is underway. Methods: Key eligibility criteria are age ≥18 years; previously untreated unresectable or metastatic HER2+ (centrally confirmed IHC 3+ or IHC 2+/ISH > 2.0) G/GEJ cancer; life expectancy > 6 months with RECIST v1.1 measurable disease; and adequate organ function and performance status (ECOG PS of 0 or 1). Patients will be randomly assigned 1:1 to receive chemotherapy with pembrolizumab 200 mg intravenously (IV) or placebo with trastuzumab 6 mg/kg (after 8 mg/kg load) every 3 weeks (Q3W) up to 2 years or until intolerable toxicity or disease progression. Investigator-choice chemotherapy will include day 1 cisplatin 80 mg/m2 IV and 5-fluorouracil 800 mg/m2/day IV (days 1-5) or oxaliplatin 130 mg/m2 IV and capecitabine 1000 mg/m2 BID days 1-14 (Q3W). Primary end points are progression-free survival and overall survival. Secondary end points are objective response rate, duration of response, and safety and tolerability. Adverse events are graded per CTCAE v4.0 and will be monitored for 30 or 90 days after treatment. Patients will be followed up for survival. Planned enrollment is approximately 692 patients. Clinical trial information: NCT03615326.

Association of co-occurring gene alterations and clinical activity of rucaparib in patients with BRCA1 or BRCA2 mutated (BRCA+) metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 80-80
Author(s):  
Wassim Abida ◽  
Akash Patnaik ◽  
David Campbell ◽  
Jeremy David Shapiro ◽  
Alan Haruo Bryce ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Specific Antigen ◽  
Response Rates ◽  
Clinical Activity ◽  
Plasma Samples ◽  
Tp53 Mutations ◽  
Measurable Disease ◽  
Psa Response

80 Background: The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib was granted accelerated approval by the US Food and Drug Administration for patients with BRCA+ mCRPC based on results from the phase 2 TRITON2 study (NCT02952534). The TP53 tumor suppressor gene is among the most frequently mutated genes in human cancers, including mCRPC, and alterations in TP53, PTEN, and RB1 are associated with poor prognosis in patients with prostate cancer and other tumor types. We present data on co-occurring alterations in patients with BRCA+ mCRPC treated with rucaparib in TRITON2. Methods: Patients had progressed on 1–2 lines of androgen receptor-directed therapy and 1 taxane-based chemotherapy and were treated with rucaparib 600 mg BID. Tissue and/or cell-free DNA extracted from plasma samples were profiled comprehensively for genomic alterations using Foundation Medicine, Inc., next-generation sequencing assays. Objective response rate (ORR) was assessed per modified Response Evaluation Criteria in Solid Tumors and Prostate Cancer Working Group 3 criteria by independent radiologic review of patients with measurable disease. Prostate-specific antigen (PSA) response rate (≥50% decrease from baseline) was assessed in all patients. Results: Tissue and/or plasma samples were available for 114/115 patients with BRCA+ mCRPC (visit cutoff date: Dec. 23, 2019). Among patients with BRCA+ mCRPC who had samples available for comprehensive genomic profiling, 36.8% (42/114) had a co-occurring alteration in TP53. Deleterious alterations in PTEN were observed in 34.2% (39/114) of patients, 44% (17/39) of which were homozygous deletions of PTEN. RB1 loss was observed in 12.3% (14/114) of patients and was seen more frequently in patients with measurable disease (18.0%, 11/61) than in patients with non-measurable disease (5.7%, 3/53). Although patients with and without TP53 mutations had generally similar baseline demographics and disease characteristics, visceral disease was more prevalent in patients with TP53 mutations (54.8%; 23/42) than in those without them (29.2%; 21/72). Similar ORR and PSA response rates were seen in patients with BRCA+ mCRPC with or without TP53 mutation, with a non-significant trend towards lower response rates in patients with co-occurring TP53 alterations. Conclusions: Results from TRITON2 showed antitumor activity for rucaparib in patients with BRCA+ mCRPC associated with or without co-occurring alterations in TP53. Demographics and additional efficacy analyses in genomic subgroups with co-occurring alterations in TP53, PTEN, and RB1 will be reported. Clinical trial information: NCT02952534. [Table: see text]

Double-Blinded Randomized Study of High-Dose Calcitriol Plus Docetaxel Compared With Placebo Plus Docetaxel in Androgen-Independent Prostate Cancer: A Report From the ASCENT Investigators

2007 ◽  
Vol 25 (6) ◽  
pp. 669-674 ◽  
Author(s):  
Tomasz M. Beer ◽  
Christopher W. Ryan ◽  
Peter M. Venner ◽  
Daniel P. Petrylak ◽  
Gurkamal S. Chatta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Hazard Ratio ◽  
High Dose ◽  
Weekly Docetaxel ◽  
End Point ◽  
Psa Response ◽  
Grade 3 ◽  
Androgen Independent

Purpose To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. Patients and Methods Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. Results Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%). Conclusion This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.

Docetaxel and curcuminoids (CCM) combination in patients with castration-resistant prostate cancer (CRPC): A phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16021-e16021
Author(s):  
Hakim Mahammedi ◽  
Mélanie Pouget ◽  
Eloise Planchat ◽  
Herve Cure ◽  
Xavier Durando ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Combination Methods ◽  
Psa Response

e16021 Background: Prostate cancer is a major problem in the aging male population. Docetaxel, the first-line reference treatment in CRPC induces a prostate-specific antigen (PSA) response in 45% of patients and an objective tumor response in 12%. Preclinical studies suggested that curcuminoids inhibit tumor metastasis, invasion and angiogenesis and reverse drug resistance. We wanted to potentiate docetaxel by curcuminoïds in CRPC first line. Our previous phase I study showed the safety and the tolerability of CCM associated to docetaxel for advanced breast cancers. We have conducted in 2009-2010 a phase II study to assess the response of CRPC to this combination. Methods: Patients (n=30) with progressing CRPC and rising PSA were enrolled to receive the experimental treatment. Docetaxel was given in standard conditions (75mg/m², 1h i.v infusion every 3 weeks for 6 cycles + prednisolone) with CCM orally at the dose of 6gr/day (7 days by cycle: d-4 to d+2). The primary endpoint was response rate assessed by biological and paraclinical examinations. The secondary endpoints included safety, time to progression and compliance. Twenty nine patients were evaluable on PSA assessment and 15 on RECIST criteria. Results: 26 patients received the treatment totality and 4 withdrew prematurely. No patient withdrew for toxicity (2 deaths and 2 PSA progressions). A PSA response was observed in 17/29 patients (59%) (4 complete and 13 partial) observed rapidly (before the 3rd cycle) for 15 patients. The median time to subsequent PSA progression (TTP) was 5.8 months. Six patients (40%) had a partial objective response and 9 (60%) a stable disease. The median TTP on targets was 7.85 months (n=13/15). The regimen was well tolerated, with uncommon grade 3/4 toxicity; no adverse event was attributed to CCM. Of 169 cycles, 150 (89%) were completed with perfect compliance. Overall survival was 19 months (mean) and 24 months (median) with 17 events as of december 2012. Conclusions: These results are promising in improving the response rate to docetaxel in terms of both PSA decrease and objective response, with good tolerability and acceptability of CCM. A randomized trial is necessary to confirm this results. Clinical trial information: NCT01012141.

Weekly High-Dose Calcitriol and Docetaxel in Metastatic Androgen-Independent Prostate Cancer

2003 ◽  
Vol 21 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Tomasz M. Beer ◽  
Kristine M. Eilers ◽  
Mark Garzotto ◽  
Merrill J. Egorin ◽  
Bruce A. Lowe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Agent ◽  
Specific Antigen ◽  
High Dose ◽  
Time To Progression ◽  
Oral Hydration ◽  
Phase Ii Studies ◽  
Measurable Disease ◽  
Psa Response ◽  
Androgen Independent

Purpose: To determine the safety and efficacy of weekly high-dose oral calcitriol (Rocaltrol, Roche Pharmaceuticals, Basel, Switzerland) and docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen-independent prostate cancer (AIPC).Patients and Methods: Thirty-seven patients were treated with oral calcitriol (0.5 μg/kg) on day 1 followed by docetaxel (36 mg/m2) on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients maintained a reduced calcium diet and increased oral hydration. Prostate-specific antigen (PSA) response was the primary end point, which was defined as a 50% reduction in PSA level confirmed 4 weeks later.Results: Thirty of 37 patients (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty-two patients (59%; 95% CI, 43% to 75%) had a confirmed > 75% reduction in PSA. Eight of the 15 patients with measurable disease (53%; 95% CI, 27% to 79%) had a confirmed partial response. Median time to progression was 11.4 months (95% CI, 8.7 to 14 months), and median survival was 19.5 months (95% CI, 15.3 months to incalculable). Overall survival at 1 year was 89% (95% CI, 74% to 95%). Treatment-related toxicity was generally similar to that expected with single-agent docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected by the presence of its companion drug in an exploratory substudy.Conclusion: The combination of weekly oral high-dose calcitriol and weekly docetaxel is a well-tolerated regimen for AIPC. PSA and measurable disease response rates as well as time to progression and survival are promising when compared with contemporary phase II studies of single-agent docetaxel in AIPC. Further study of this regimen is warranted.

scholarly journals Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration

2020 ◽  
Vol 38 (32) ◽  
pp. 3763-3772 ◽  
Author(s):  
Wassim Abida ◽  
Akash Patnaik ◽  
David Campbell ◽  
Jeremy Shapiro ◽  
Alan H. Bryce ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Specific Antigen ◽  
Brca2 Gene ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Measurable Disease ◽  
Psa Response

PURPOSE BRCA1 or BRCA2 ( BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. METHODS We enrolled patients who progressed after one to two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. RESULTS Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). CONCLUSION Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.

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