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.

Response to low-dose ketoconazole and subsequent dose escalation to high-dose ketoconazole in patients with androgen-independent prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4646-4646
Author(s):  
M. Nakabayashi ◽  
W. Xie ◽  
M. M. Regan ◽  
D. M. Jackman ◽  
P. W. Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Dose Escalation ◽  
Low Dose ◽  
Specific Antigen ◽  
High Dose ◽  
Time To Progression ◽  
Subsequent Dose ◽  
Psa Response ◽  
Androgen Independent

4646 Background: High dose ketoconazole (HDK) in combination with steroids has been recognized as an effective secondary hormonal therapy in androgen independent prostate cancer (AIPC). However, HDK causes more severe adverse events than low dose ketoconazole (LDK). Relatively little is known about the efficacy of LDK in AIPC. We evaluated the efficacy of LDK and of subsequent dose escalation from LDK to HDK as secondary hormonal therapy in patients with AIPC. Methods: We retrospectively identified patients with AIPC in a single institution treated with LDK (200 mg PO TID) as secondary hormonal therapy with or without concomitant steroids. Additionally, patients were identified who received dose escalation to HDK (400 mg PO TID) after experiencing a rising prostate-specific antigen (PSA). Results: 138 patients were eligible for the study. Median age was 64 years (range: 41–84); median PSA at initiation of ketoconazole was 37.4 ng/ml (range: 0.8–2279). Patients received LDK as either second (25.4%), third (50.0%) or fourth (21.7%) line hormonal therapy. Thirty-nine of 138 patients (28.3%, 95% CI 20.9%–36.6%) treated with LDK treatment experienced PSA declines ≥50%. Median duration of LDK was 6.4 months in responders and 2.9 months in non-responders. Dose escalation to HDK subsequently was performed in 55 (40%) patients, seven of whom (12.7%) demonstrated a subsequent PSA decline ≥50% (5 LDK responders and 2 LDK non-responders, respectively). Overall time to progression with LDK with or without dose escalation was 3.5 months (range 0.1+–61 months). The most common reversible adverse effect on LDK was grade 1 or 2 fatigue (12.3%). 41.8% of dose escalation group experienced either aggravation or development of toxicities. The most common toxicities on HDK were nausea (16.4%) and fatigue (14.5%). Conclusions: LDK is associated with a PSA response rate comparable to HDK as secondary hormonal therapy in patients with AIPC, and appears to be less toxic. Few patients responded to the dose escalation from LDK to HDK but durable additional responses occurred in some. No significant financial relationships to disclose.

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.

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.

Timing of docetaxel chemotherapy and impact on outcomes in metastatic castrate-resistant prostate cancer (MCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 298-298
Author(s):  
Alastair Thomson ◽  
Adam Pollard ◽  
Frances May Mark
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Specific Antigen ◽  
Response Rates ◽  
Treated Group ◽  
Patient Choice ◽  
Gleason Grade ◽  
Psa Response ◽  
Number Of Cycles

298 Background: Docetaxel use has led to a significant prolongation in overall survival (OS) in metastatic prostate cancer after castrate resistance, with a more substantial OS gain when used in combination with initial androgen deprivation therapy (ADT). There is however limited information on outcomes in patients who initially do not receive chemotherapy, perhaps through patient choice or impaired performance status, who become suitable for docetaxel, comparing earlier with later docetaxel treatment. Methods: We retrospectively reviewed patients’ electronic clinical and prescribing records diagnosed with MCRPC and treated with docetaxel from 01/01/2006 to 24/11/2016 in a single centre in the UK. Data was reviewed for number of individual treatments received pre and post chemotherapy, including initial ADT, enzalutamide, abiraterone, docetaxel, cabazitaxel, mitoxantrone, radium 223, single agent steroids and diethylstilboestrol. Prostate specific antigen (PSA) response, number of cycles and dosing of docetaxel and OS were also reviewed. Results: 168 consecutive patients with MCRPC receiving docetaxel were reviewed. Median Gleason grade across the three groups was 8. 48 patients (29%) received docetaxel after 1 or 2 previous treatments, 105 (63%) after 3 or 4 previous treatments and 15 (9%) after 5 or 6. PSA response rates were superior in the earlier treated group (61%, p=0.003), compared with 30% and 31% respectively in the later groups. Median number of cycles was 5.5 overall, with a mean weighted dose received of 396mg/m2, 373mg/m2 and 301mg/m2 in the after 1 or 2 treatments, after 3 or 4 treatments and after 5 or 6 treatment groups. Median OS from castrate resistance for the earlier group was 29 months, not significantly less (p=0.1) than the 35 months for an intermediate number of prior treatments and 42 months for the later treated group. Conclusions: In this group of patients in routine clinical practice who do not receive docetaxel with initial ADT, PSA response rates are significantly improved and overall dose received is higher with subsequent earlier use. However, overall survival is not significantly different between the early and later docetaxel treated patients.

scholarly journals Phase II Trial of Bevacizumab, Thalidomide, Docetaxel, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (12) ◽  
pp. 2070-2076 ◽  
Author(s):  
Yang-Min Ning ◽  
James L. Gulley ◽  
Philip M. Arlen ◽  
Sukyung Woo ◽  
Seth M. Steinberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Phase Ii ◽  
Specific Antigen ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Castration Resistant ◽  
Phase Ii Studies

Purpose We previously demonstrated that thalidomide appears to add to the activity of docetaxel in metastatic castration-resistant prostate cancer (CRPC). Phase II studies combining docetaxel with bevacizumab have had substantial antitumor activity. We hypothesized that the combination of docetaxel plus these antiangiogenic drugs with different targets would have substantial clinical activity. To explore safety and efficacy, this was tested in mice and in human patients. Patients and Methods Preclinical efficacy of the combination therapy was evaluated in PC3 xenograft mice. Sixty patients with progressive metastatic CRPC received intravenous docetaxel and bevacizumab plus oral thalidomide and prednisone. The primary end point was a prostate-specific antigen (PSA) decline of ≥ 50%. Secondary end points included time to progression, overall survival, and safety. Results In the mouse model, combination therapy of docetaxel, bevacizumab, and thalidomide inhibited tumor growth most effectively. In the clinical trial, 90% of patients receiving the combination therapy had PSA declines of ≥ 50%, and 88% achieved a PSA decline of ≥ 30% within the first 3 months of treatment. The median time to progression was 18.3 months, and the median overall survival was 28.2 months in this group with a Halabi-predicted survival of 14 months. While toxicities were manageable, all patients developed grade 3/4 neutropenia. Conclusion The addition of bevacizumab and thalidomide to docetaxel is a highly active combination with manageable toxicities. The estimated median survival is encouraging, given the generally poor prognosis of this patient population. These results suggest that definitive clinical trials combining antiangiogenic agent combinations with docetaxel are warranted to improve treatment outcomes for patients with metastatic CRPC.

A phase II trial in progress: Pamiparib, an investigational PARP inhibitor, in patients with metastatic castration-resistant prostate cancer and a circulating tumor cell homologous recombination deficiency (HRD) phenotype or BRCA defects.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS328-TPS328
Author(s):  
Simon Chowdhury ◽  
Joaquin Mateo ◽  
Mitchell Gross ◽  
Andrew J. Armstrong ◽  
Marcia Cruz-Correa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Metastatic Disease ◽  
Parp Inhibitor ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Measurable Disease ◽  
Psa Response

TPS328 Background: Men with metastatic castration-resistant prostate cancer (mCRPC) who have a BRCA1/2 mutation ( BRCA1/2mut) or mutations in other HRD genes have a poor prognosis. The EPIC liquid biopsy test is a novel assay that can identify circulating tumor cells (CTC) with HRD associated phenotypes. Preliminary studies have shown that these men may respond to treatment with a PARP inhibitor. Pamiparib is an investigational PARP1/2 inhibitor that has shown brain penetration and potent PARP–DNA complex trapping in nonclinical studies. In early phase clinical studies (NCT02361723; NCT03333915), pamiparib was generally well tolerated and showed preliminary antitumor activity; 60 mg orally twice daily (BID) was established as the recommended investigational dose. Methods: This open-label, global, phase 2 study (NCT03712930) will evaluate antitumor activity and safety of pamiparib in mCRPC pts with CTC-HRD, assessed by the EPIC CTC-HRD assay, or deleterious germline/somatic BRCA1/2mut status. Patients must have progressed on/after ≥1 androgen receptor-targeted therapy, have received ≥1 taxane-based therapy, and have prostate-specific antigen (PSA) progression per PCWG3 criteria. Four cohorts of patients will receive pamiparib 60 mg BID in 28-day cycles. Cohort 1 will include ~50 pts with CTC-HRD+ +/- BRCA1/2mut mCRPC with measurable metastatic disease; Cohort 2 will include ~30 pts with CTC-HRD+ +/- BRCA1/2mut mCRPC with bone-only disease; Cohorts 3 & 4 will include ~20 pts with CTC-HRD-/unknown + BRCA1/2mut mCRPC with measurable metastatic disease (Cohort 3), or bone-only disease (Cohort 4). Disease status will be assessed every 8 wks for 24 wks, then every 12 wks; PSA levels will be tested every 4 wks. Co-primary endpoints are radiographic ORR assessed by IRC (pts with measurable disease) and confirmed PSA response rate per PCWG3 criteria (pts +/- measurable disease). Secondary endpoints include ORR, time to PSA response/progression, duration of PSA response, time to symptomatic skeletal event, radiographic progression-free survival, overall survival, and safety. Clinical trial information: NCT03712930.

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]

Prospective evaluation of hydrocortisone and suramin in patients with androgen-independent prostate cancer.

1995 ◽  
Vol 13 (9) ◽  
pp. 2208-2213 ◽  
Author(s):  
W K Kelly ◽  
T Curley ◽  
C Leibretz ◽  
A Dnistrian ◽  
M Schwartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Specific Antigen ◽  
Intermittent Infusion ◽  
Measurable Disease ◽  
Bone Scans ◽  
To Receive ◽  
Androgen Independent

PURPOSE To assess efficacy of intermittent infusion of suramin in patients with androgen-independent prostate cancer who have had disease progression on hydrocortisone. PATIENTS AND METHODS Chemotherapy-naive patients with progressive androgen-independent prostate cancer were given hydrocortisone 40 mg/d and monitored for treatment effect. At the time of disease progression, suramin was administered on a pharmacokinetically derived, 2-week dosing schedule. RESULTS Thirty patients with a median Karnofsky performance status (KPS) of 90% were treated with hydrocortisone. No responses were seen in 12 patients with measurable disease or 29 patients with abnormal bone scans. Thirty patients had an increasing prostate-specific antigen (PSA) level before treatment and six (20%) had a more than 50% decline in PSA from the baseline value for a median of 16 weeks (range, 12 to 52+). Twenty-eight patients had disease progression after a median of 7 weeks (range, 3 to 23), and two patients have continued to receive hydrocortisone for 44 and 52 weeks. Twenty-eight patients received hydrocortisone and suramin, with median suramin concentrations of 97 to 170 micrograms/mL for 4 weeks. No responses in measurable disease and no improvements in bone scans were seen. Five patients (18%) showed a more than 50% decline in PSA levels from baseline, of whom three had previously responded to hydrocortisone. Only two of 24 patients who did not show a posttherapy decline in PSA levels after hydrocortisone had a reduction in PSA levels with the addition of suramin. Toxicity profiles were acceptable with each agent, although a higher proportion of subjects showed hematologic, cardiac, and neurologic events when suramin was added. CONCLUSION Suramin has limited efficacy in patients with androgen-independent prostate cancer who have had disease progression after hydrocortisone.

Safety and efficacy of the combination of high-dose calcitriol, docetaxel and aoledronic acid in hormone-refractory prostate cancer (HRPC): Interim report of a phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14600-14600
Author(s):  
A. Shamseddine ◽  
J. Makarem ◽  
Z. Abdel Khalik ◽  
M. Bulbul ◽  
A. Taher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Disease Progression ◽  
Specific Antigen ◽  
Response Analysis ◽  
High Dose ◽  
Weekly Basis ◽  
Psa Response ◽  
Grade Ii ◽  
Grade Iii

14600 Background: The purpose of this study is to assess the efficacy and safety of Calcitriol, Docetaxel and Zoledronic acid in patients with metastatic HRPC. The primary endpoint of the study is the toxicity profile. Secondary endpoints include prostate specific antigen PSA response and time to disease progression. Methods: 16 patients with HRPC were enrolled. All patients had confirmed diagnosis of prostate cancer and no previous cytotoxic therapy. All patients signed an informed consent. Patients received oral Calcitriol 0.5μg/kg on day 1 on weekly basis six out of eight-week cycles, Docetaxel 36mg/m2 on day 2 on weekly basis six out of eight-week cycles, and Zoledronic acid 4mg intravenously on weeks 1 and 5 of every 8-week cycle. Results: A total of 52 cycles were administered and toxicity was acceptable. No treatment-related mortality was encountered. No grade IV anemia, neutropenia, thrombocytopenia or diarrhea was reported. No grade IV gastrointestinal toxicities or thromboembolic events were reported. Grade IV infection was seen in 2 (3.8%) cycles (herpetic esophagitis and listeria meningitis). Grade III neutropenia was seen in 2 cycles (3.8%). Grade III diarrhea was seen in 1 cycle (1.9%) and grade II diarrhea in 4 cycles (7.7%). Grade II to III nausea and vomiting was reported in 8 cycles (15.4%). Grade II to III sensory neuropathy was noted after 17 cycles (32.7%). Grade III fatigue was reported in 5 cycles (9.6%). 14 patients were eligible for response analysis. Overall PSA response rate of our patients was 57.2%. Median time to disease progression was 6.5 months (range 2–15). One year survival was 57.1% (8 out of 14 patients). Conclusions: This interim analysis showed that the addition of Calcitriol to Docetaxel showed an acceptable safety profile as compared to Docetaxel regimens alone with less incidence of neutropenia and diarrhea. Previous studies using Docetaxel alone has reported higher incidence of neutropenia reaching 43–56% and grade III to IV diarrhea (10–34%). Our study suggests that Calcitriol might have a protective effect against the Docetaxel toxicities. No significant financial relationships to disclose.

A phase I open-label, dose escalation study to determine the maximum tolerated dose and to evaluate the safety profile of lenalidomide with every three week docetaxel in subjects with androgen independent prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14618-14618 ◽  
Author(s):  
R. A. Moss ◽  
G. Shelton ◽  
J. Melia ◽  
S. G. Mohile ◽  
D. P. Petrylak
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Dose Escalation ◽  
Specific Antigen ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Narcotic Analgesics ◽  
Dose Escalation Study ◽  
Measurable Disease ◽  
Androgen Independent

14618 Background: Based on the known efficacy of docetaxel (D) in Androgen Independent Prostate Cancer (AIPC), and demonstrated activity of the antiangiogenesis agent thalidomide in combination with docetaxel, a Phase I trial in patients (pts) with AIPC with evidence of progression by unidimensionally measurable disease or rising serum Prostate Specific Antigen (PSA) levels after antiandrogen withdrawal was designed. The study evaluates the combination of escalating doses of D and lenalidomide (Ln), a derivative of thalidomide with immunomodulatory and antiangiogenic properties. Pts were permitted to have no more than two prior chemotherapy regimens. Methods: Pts were given D and Ln on a q3 week dose-escalation schedule. Dose Levels of D (mg/m2): Level (L) 1 = 60 L2-L5 =75, given IVPB over 60 minutes in combination with prednisone 5mg po bid. Decadron 20 mg was given 12, 6 hrs and 15 minutes prior to D on D#1. Dose of Ln (mg/day) on D#1–14 of 21-day cycle: L 1 = 10 mg, L2= 10 mg, L3 = 15 mg, L4–20 mg L5 = 25 mg. Patient Characteristics: L1: N = 5. Median Age 66.2 yrs. Median PSA = 101.9 (range 5.9–164.0). Prior CT: none. Prior palliative RT: none. Patients with unidimensionally measurable disease: 4, all in lymph nodes. Patients with bone metastases: 5. Pre-treatment, 1 patient required narcotic analgesics. Results: Five L1 patients are evaluable for toxicity and response. Median number of cycles administered = 4 (range 2–5). Toxicity: There have been no Grade (G) 3 or 4 toxicities. Anti-tumor activity: Two pts (40%) have had a greater than 50% decline in serum PSA on 2 consecutive measurements at least 2 weeks apart. Of 4 pts with unidimensionally measurable disease, all have stable disease by RECIST criteria. Conclusions: At L1, D + Ln has been well tolerated in AIPC. Further dose escalation to L2 and above is planned. [Table: see text]

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