Severe zoledronic acid (ZOL)-associated hypophosphatemia and prognosis in patients with castration-resistant prostate cancer (CRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15180-e15180
Author(s):  
Julia Warr ◽  
David Yam ◽  
Leah VanDraanen ◽  
Shannon Goodall ◽  
Angie Giotis ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Fibroblast Growth Factor 23 ◽  
Symptom Control ◽  
Bisphosphonate Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Patient Demographics ◽  
Castration Resistant ◽  
Disease Characteristics ◽  
Grade 3 ◽  
Worse Prognosis

e15180 Background: ZOL therapy is associated with severe (i.e., grade ≥ 3) hypocalcemia and hypophosphatemia in a subset of patients with metastatic CRPC. However, as opposed to the distinct clinical picture of hypocalcemia, the symptoms of hypophosphatemia are less pathognomonic. Furthermore, serum phosphate abnormalities are not regularly reported. Methods: To characterize the rate and clinical impact of severe hypophosphatemia in CRPC patients undergoing ZOL therapy, we identified CRPC patients receiving at least 3 doses of ZOL at our Centre between 01/2004 and 03/2011. Patient demographics, disease characteristics and laboratory parameters were extracted using the Oncology Symptom Control and Information Resource database, and by means of manual chart review. Results: 12 of 90 evaluable patients developed grade ≥ 3 hypophosphatemia (nadir) after 364±299 days (mean±SD) following the first dose of ZOL. While only one patient presented with concomitant severe hypocalcemia, the hypophosphatemia nadir coincided with rising PSA readings in 9 out of 11 informative patients. Severe ZOL-associated hypophosphatemia identified patients with worse outcome (median overall survival from time of CRPC diagnosis to death 685 days) compared to patients without documented hypophosphatemia (907 days, HR 0.52, p=0.049; n=42), or patients with grade 1-2 hypophosphatemia (1035 days, HR 0.44, p=0.016; n=36). Otherwise, the prognostic nomogram developed by Armstrong et al appears not to capture the poor prognosis of patients with severe ZOL-associated hypophosphatemia. Conclusions: Grade 3-4 hypophosphatemia occurs in about 15% of CRPC patients undergoing ZOL therapy and is associated with worse prognosis when compared to patients with absent or mild hypophosphatemia. The latter is usually transient and likely related to increased parathyroid hormone levels due to calcium decreases as a consequence of bisphosphonate therapy. On the other hand, the distinct clinical behavior of CRPC presenting with ZOL-associated severe hypophosphatemia suggests that secreted tumor-associated factors such as fibroblast growth factor 23 may contribute to this phenomenon.

Use of zoledronic acid therapy–associated severe hypophosphatemia to identify poor-prognosis patients with metastatic castration-resistant prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 58-58
Author(s):  
Julia Warr ◽  
David Yam ◽  
Shannon Goodall ◽  
Leah VanDraanen ◽  
Angie Giotis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Chart Review ◽  
Symptom Control ◽  
Castration Resistant Prostate Cancer ◽  
Acid Therapy ◽  
Patient Demographics ◽  
Castration Resistant ◽  
Late Event ◽  
Grade 3

58 Background: Zoledronic acid (ZOL) therapy is associated with severe (i.e., grade 3/4 according to CTCAEv4.0) hypocalcemia and hypophosphatemia in a subset of patients with metastatic castration-resistant prostate cancer (mCRPC) to bone. However, as opposed to the distinct clinical picture of hypocalcemia, the symptoms of hypophosphatemia are less pathognomonic. Furthermore, the rate of hypophosphatemia is not regularly reported. Methods: To characterize the rate and circumstances of severe hypophosphatemia in mCRPC patients undergoing ZOL therapy, we identified mCRPC patients receiving at least 3 doses of ZOL therapy at our Centre between 2004 and 03/2011. Patient demographics, disease and laboratory parameters were extracted by using the Oncology Symptom Control and Information Resource database, and by means of manual chart review. Results: 11 of 112 patients (10%) developed grade 3/4 hypophosphatemia (nadir) after 241±223 days (mean±SD) following the first dose of ZOL. Only one patient presented with concomitant severe hypocalcemia. Interestingly, the hypophosphatemia nadir coincided with rising PSA readings in 9 out of 10 informative patients. Furthermore, ZOL-associated severe hypophosphatemia identified mCRPC patients with worse outcome (time from CRPC diagnosis to death 628±317 days, versus 901±526 days in CRPC patients without severe ZOL-associated hypophosphatemia, p < 0.028). Conclusions: 10% of mCRPC patients undergoing ZOL therapy presented with grade 3/4 hypophosphatemia. While hypocalcemia usually occurs within the first 6 months of ZOL therapy, ZOL-associated severe hypophosphatemia is a relatively late event. It appears to occur at the time of disease progression and is associated with a poor outcome.

Disease characteristics and outcome of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received a beta emitter (177Lu-PSMA) after an alpha emitter (radium-223).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17592-e17592
Author(s):  
A. Oliver Sartor ◽  
Christian la Fougère ◽  
Markus Essler ◽  
Samer Ezziddin ◽  
Gero Kramer ◽  
...  
Keyword(s):  
Castration Resistant Prostate Cancer ◽  
Investigational Agent ◽  
Castration Resistant ◽  
Disease Characteristics ◽  
Radium 223 ◽  
Alpha Emitter ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Favorable Safety

e17592 Background: Ra-223, a targeted alpha therapy, showed an overall survival (OS) benefit and favorable safety profile in mCRPC pts in a phase 3 trial. 177Lu-PSMA radioligand is an investigational agent for mCRPC. REASSURE (NCT02141438) is a global, prospective, observational study investigating Ra-223 safety in routine clinical practice over 7 years’ follow-up in mCRPC pts. Data from the second prespecified interim analysis (IA) were used to investigate safety and outcomes of pts who received 177Lu-PSMA after Ra-223 therapy. Methods: Data cut-off for the second prespecified IA was March 2019, and included pts who had subsequent 177Lu-PSMA after the last Ra-223 dose. Disease characteristics, adverse events (AEs) after last Ra-223 dose, and OS are described. Results: Of 1465 pts overall, 26 received 177Lu-PSMA subsequent to Ra-223. In this subgroup, pts received multiple anticancer therapies prior to 177Lu-PSMA. 13 pts (50%) received Ra-223 as combination therapy at second line (metastatic setting). Pts received a median of six Ra-223 doses. After Ra-223 treatment ended, 3 pts (12%) had drug-related serious AEs, 9 pts (35%) had grade 3/4 bone marrow suppression-relevant hematologic AEs. Median duration of 177Lu-PSMA treatment was 3.5 months. 19 pts (73%) received 177Lu-PSMA as fourth-line therapy or onwards. OS was 28.0 months from start of Ra-223 and 13.2 months from start of 177Lu-PSMA. Conclusions: In this select population receiving a sequence of multiple lines of therapy with different modes of action, grade 3/4 hematologic AEs after Ra-223 were low. Treatment with subsequent 177Lu-PSMA seems feasible, based on duration of 177Lu-PSMA and survival. Clinical trial information: NCT02141438 . [Table: see text]

scholarly journals Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Node Metastases ◽  
Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

scholarly journals Abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of ‘real-life’ studies

2018 ◽  
Vol 10 (10) ◽  
pp. 305-315 ◽  
Author(s):  
Michele Marchioni ◽  
Petros Sountoulides ◽  
Maida Bada ◽  
Sebastiano Rapisarda ◽  
Cosimo De Nunzio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Meta Analysis ◽  
Real Life ◽  
Castration Resistant Prostate Cancer ◽  
The Real ◽  
Castration Resistant ◽  
Real Life Setting ◽  
Grade 3 ◽  
Baseline Psa

Background: To assess the efficacy and safety of treatment with abiraterone acetate (AA) in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) in the ‘real-life’ setting. Methods: Data acquisition on the outcomes of the use of AA in chemotherapy-naive patients with mCRPC was performed by a MEDLINE comprehensive systematic literature search using combinations of the following key words: ‘prostate cancer’, ‘metastatic’, ‘castration resistant’, ‘abiraterone’, ‘real life’, and excluding controlled clinical trials (phase II and III studies). Identification and selection of the studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were overall survival (OS), progression-free survival (PFS), 12-week 50% reduction in prostate-specific antigen (PSA), and grade 3 and higher adverse events. Data were narratively synthesized in light of methodological and clinical heterogeneity. Results: Within the eight identified studies that fulfilled the criteria, a total of 801 patients were included in the meta-analysis. Baseline PSA ranged between 9.5 and 212.0 ng/ml. Most of the patients had bone metastases. Duration of treatment with AA was longer in the studies with lower baseline PSA levels. The median OS ranged between 14 and 36.4 months. The PFS, assessed according to different definitions, ranged from 3.9 to 18.5 months. A 50% PSA reduction at 12 weeks was reached by a variable percentage of patients ranging from 36.0% to 62.1%. Finally, the rate of grade 3 and higher adverse events was reported in three studies and ranged from 4.4% to 15.5%. Conclusions: Despite the high grade of heterogeneity among studies, treatment with AA seems to ensure good survival outcomes in the ‘real-life’ setting. However, prospective studies based on patients’ characteristics being more similar to ‘real-life’ patients are necessary.

Pembrolizumab plus enzalutamide for enzalutamide-resistant metastatic castration-resistant prostate cancer (mCRPC): Updated analyses after one additional year of follow-up from cohorts 4 and 5 of the KEYNOTE-199 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5042-5042
Author(s):  
Julie N Graff ◽  
Scott T. Tagawa ◽  
Christopher J. Hoimes ◽  
Winald R. Gerritsen ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Safety Data ◽  
Standard Of Care ◽  
Castration Resistant Prostate Cancer ◽  
Fisher Syndrome ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Phase 2 Study ◽  
Grade 3

5042 Background: KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study to evaluate pembrolizumab (pembro) in mCRPC. A previous analysis of patients with RECIST-measurable (cohort 4 [C4]) or bone-predominant nonmeasurable (cohort 5 [C5]) disease who were chemotherapy-naive and had progression while on enzalutamide (enza) found that pembro + enza showed antitumor activity and manageable safety. Long-term outcomes are of interest with immunotherapy; hence, updated efficacy and safety data after an additional 1 year of follow-up are presented. Methods: Pts were eligible if they had resistance to enza after prior response. Prior treatment with abiraterone was allowed. Pts received pembro 200 mg Q3W for up to 35 cycles + enza QD until progression, unacceptable toxicity, or withdrawal. Primary end point was ORR per RECIST v1.1 by blinded independent central review (BICR) in C4. Secondary end points were DOR (C4), and DCR, rPFS, OS and safety (both cohorts). Results: 126 pts (C4, 81; C5, 45) were treated. Median age was 72 years (range 43-92), 32.5% had visceral disease and 87.3% previously received ≥6 mo of enzalutamide; 121 pts (96.0%) discontinued, most because of progressive disease. Median (range) time from enrollment to data cutoff was 31.7 mo (23.1-37.1) in C4 and 35.5 mo (22.9-37.3) in C5. In C4, confirmed ORR was 12.3% (95% CI 6.1-21.5) (2 CRs, 8 PRs); median (range) DOR was 8.1 mo (2.5+ to 15.2), and 62.5% had a response ≥6 mo (Kaplan-Meier estimate). Additional efficacy analyses are outlined in the table. A total of 27.2% and 28.9% of pts in C4 and C5, respectively, experienced grade ≥3 treatment-related adverse events. Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any-grade (34.1%) and grade 3 or 4 (5.6%) rash, regardless of relatedness to treatment, was higher than previously reported for individual agents but manageable with standard-of-care treatments; 2 pts discontinued because of rash. Conclusions: After an additional 1 year of follow-up, pembro + enza continued to show antitumor activity and a manageable safety profile in pts with mCRPC who became resistant to enza. The treatment combination is being further evaluated in the ongoing phase 3 KEYNOTE-641 trial (NCT03834493). Clinical trial information: NCT02787005. [Table: see text]

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

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

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

scholarly journals Prognostic factors for patients treated with abiraterone

2020 ◽  
Vol 6 (2) ◽  
pp. FSO436 ◽  
Author(s):  
Cecília M Alvim ◽  
André Mansinho ◽  
Rita S Paiva ◽  
Raquel Brás ◽  
Patrícia M Semedo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Prognostic And Predictive Factors

Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10−0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14−0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.

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

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

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

A phase II study evaluating the efficacy and safety of single agent IMC A12, a monoclonal antibody (MAb), against the insulin-like growth factor-1 receptor (IGF-IR), as monotherapy in patients with metastastic, asymptomatic castration-resistant prostate cancer (CRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5142-5142 ◽  
Author(s):  
C. Higano ◽  
J. Alumkal ◽  
C. J. Ryan ◽  
E. Y. Yu ◽  
T. M. Beer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Single Agent ◽  
Castration Resistant Prostate Cancer ◽  
Radiologic Evaluation ◽  
Castration Resistant ◽  
Disease Stabilization ◽  
Human Igg1 ◽  
Grade 3 ◽  
Transient Elevation

5142 Background: IGF-IR-mediated signaling contributes to prostate cancer carcinogenesis and pathogenesis and may be associated with hormone resistance. IMC-A12 is a fully human IgG1 MAb that specifically targets the IGF-IR and inhibits ligand binding and signaling. In xenografts, IMC-A12 inhibits growth of both androgen-dependent and -independent prostate cancer. This phase 2, multicenter study was designed to assess the safety and antitumor activity of IMC-A12 in asymptomatic pts with metastatic CRPC who were chemotherapy-naive. Methods: Pts received IMC-A12 10 mg/kg IV every 2 wks; until evidence of progressive disease (PD), intolerable toxicity, or other withdrawal criteria were met. Radiologic evaluation was performed every 8 wks. PD by bone scan required at least 2 new lesions with confirmation at subsequent imaging per PCWG2. Results: 19 of 31 pts treated have discontinued IMC-A12, 12 due to PD. 9 of 31 pts experienced disease stabilization for ≥6 mos (range: 7.4–12.5 mos), 5 pts (3 with PSA reduction) continue on IMC-A12. The most common AEs possibly or probably related to IMC-A12, were fatigue (25.8%) and hyperglycemia (19.4%). In 4 pts cases of Grade 3 hyperglycemia was treatment related none requiring discontinuation of IMC-A12; 1 pt required insulin but continued on study. Approximately 70% of pts experienced at least transient elevation of nonfasting glucose to above normal range. Other AEs grade ≥3 at least possibly related to IMC-A12 were one case each of thrombocytopenia (requiring IMC-A12 discontinuation), hyperkalemia, fatigue, pneumonia (resulting in death), and Grade 4 pharmacokinetic and pharmacodynamic analayses are pending leukoencephalopathy (probably related; requiring IMC-A12 discontinuation). Pharmakinetic and pharmacodynamic analyses are pending. Conclusions: IMC-A12 monotherapy appears well tolerated in pts with metastatic asymptomatic CRPC. As in phase I, hyperglycemia was largely asymptomatic and manageable. Disease stabilization for > 6 months in 9 of 31 pts suggests that IMC- A12 may have modest antitumor activity. Additional studies of IMC-A12 in CRPC are planned. [Table: see text]

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