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- Thellenberg-Karlsson, Camilla, 1972-, et al.
(författare)
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A randomised, double-blind, dose-finding, phase II multicentre study of ODX in the treatment of patients with castration-resistant prostate cancer and skeletal metastases
- 2023
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 181, s. 198-207
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study aimed to assess the efficacy and safety of ODX, a novel, cytotoxic, bone-targeting drug candidate, in castration-resistant prostate cancer bone metastatic disease.Methods: Patients with progressive disease were randomised to ten cycles of ODX, intravenous infusion Q2W (3, 6, and 9 mg/kg, respectively). The primary objective was to assess the relative change from baseline in bone alkaline phosphatase (B-ALP) and serum-aminoterminal-propeptide of Type I procollagen (S-P1NP) at 12 weeks. The inclusion criteria selected were broad, and a double-blind design was used to ensure objective recruitment of patients for the assessment of efficacy. None of the patients received bone-protecting agents during the ODX treatment period.Results: Fifty-five 21,20 and 14) patients were randomised to ODX (3, 6 and 9 mg/kg), respectively. The lower number of patients in arm 3 was due to too low a recruitment rate towards the end of the study. The median treatment time were 14, 13 and 14 weeks, respectively. The decrease in B-ALP at 12 weeks in study arms 3, 6 and 9 mg/kg was seen in 6/15 (40%), 8/12 (67%) and 5/12 (42%) patients, respectively, whereas the corresponding numbers for P1NP were 8/15 (53%), 8/12 (67%), and 4/12 (33%), respectively. The median decrease in B-ALP and P1NP at 12 weeks for study arms 3, 6 and 9 mg/kg were 37%, 14% and 43%, respectively, and 51%, 40% and 64%, respectively. The decrease in serum C-terminal telopeptide at 12 weeks was seen in the vast majority of patients and in about one-third of patients in bone scan index. ODX was well tolerated, and no drug-related serious adverse events occurred. There were no significant differences between study arms regarding efficacy and safety.Conclusions: ODX was well tolerated and demonstrated inhibitory effects on markers related to the vicious cycle in bone at all three doses. The reduction in metastatic burden, assessed with bone scan index, supports this finding. Studies with continued ODX treatment until disease progression are being planned (ClinicalTrials.gov Identifier: NCT02825628).
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| 2. |
- Majumder, Khairul, et al.
(författare)
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Effect on prostate volume following neoadjuvant treatment with an androgen receptor inhibitor monotherapy versus castration plus an androgen receptor inhibitor in prostate cancer patients intended for curative radiation therapy : A randomised study
- 2018
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Ingår i: Molecular and clinical oncology. - : Spandidos Publications. - 2049-9450 .- 2049-9469. ; 8:1, s. 141-146
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Tidskriftsartikel (refereegranskat)abstract
- To avoid pubic arch interference, prostate cancer patients are treated with neoadjuvant androgen deprivation therapy (ADT) to achieve prostate volume (PV) reduction prior to radiation treatment. The aim of the present randomised study was to compare the effects on PV of two regimens of ADT, an androgen receptor inhibitor monotherapy vs. castration plus an androgen receptor inhibitor. Consecutive patients with non-metastatic prostate cancer were included in a randomised neoadjuvant study, comparing an androgen receptor inhibitor monotherapy vs. castration plus an androgen receptor inhibitor. PV was assessed prior to the start of endocrine neoadjuvant treatment and prior to the start of radiation therapy (RT). PV assessment was performed by transrectal ultrasound. A total of 110 patients were included. Final sample constituted 88 (80%) patients due to lack of PV information. Castration plus an androgen receptor inhibitor was more effective in PV reduction compared with an androgen receptor inhibitor alone (P<0.001). Planning target volume decreased in the combination arm. There was no significant difference in clinical or demographic or length of neoadjuvant hormonal treatment between the groups. Overall, a significantly larger PV reduction was achieved by castration plus androgen receptor inhibitor, as compared with androgen receptor inhibitor monotherapy. The PV reduction, however, appeared not to translate into better health associated quality of life during the subsequently given curative intended combined EBRT and HDR-brachytherapy. Potential differences between these two treatments regarding anti-tumor effects on micro metastatic disease and radiation potentiating effect remains to be addressed in future prospective trials.
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| 3. |
- Rosenblatt, Robert, et al.
(författare)
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Pathologic Downstaging Is a Surrogate Marker for Efficacy and Increased Survival Following Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Urothelial Bladder Cancer
- 2012
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 61:6, s. 1229-1238
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Tidskriftsartikel (refereegranskat)abstract
- Background: Characterising responders to neoadjuvant chemotherapy (NAC) is important to minimise overtreatment and the unnecessary delay of definitive treatment of urothelial urinary bladder cancer.Objective: To assess the effect of NAC on tumour downstaging and overall survival.Design, setting, and participants: A total of 449 patients from the randomised prospective Nordic Cystectomy Trials 1 and 2 were analysed retrospectively. Eligible patients were defined as T2–T4aNXM0 preoperatively and pT0–pT4aN0−N + M0 postoperatively. The median follow-up time was 5 yr.Intervention: The experimental arm consisted of cisplatin-based NAC; the control arm consisted of cystectomy only.Measurements: The primary outcome was tumour downstaging defined as pathologic TNM less than clinical TNM. Different downstaging thresholds were applied: complete downstaging (CD) (pT0N0), noninvasive downstaging (NID) (pT0/pTis/pTaN0), and organ confinement (OC) (≤pT3aN0). Downstaging rates and nodal status were compared between the study arms using the chi-square test. Secondary outcome was overall survival (OS) stratified by treatment arm, downstaging categories, and clinical stages, analysed by the Kaplan-Meier method. The following covariates were tested as prognostic factors in univariate and multivariate analyses using the Cox regression method: age, sex, clinical stage, pN status, NAC, CD, NID, and OC.Results and limitations: Downstaging rates increased significantly in the NAC arm independent of the downstaging threshold. The impact was more prominent in clinical T3 tumours, with a near threefold increase in CD tumours. The combination of CD and NAC showed an absolute risk reduction of 31.1% in OS at 5 yr compared with CD controls. The combination of NAC and CD revealed a hazard ratio of 0.32 compared with 1.0 for the combination of no NAC and no CD. Limitations were the retrospective approach and uncertain clinical TNM staging.Conclusions: Survival benefits of NAC are reflected in downstaging of the primary tumour. Chemo-induced downstaging might be a potential surrogate marker for OS.
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