Browsing by Subject "ABIRATERONE"

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  • Kellokumpu-Lehtinen, Pirkko-Liisa; Marttila, Timo; Jekunen, Antti; Hervonen, Petteri; Klintrup, Katariina; Kataja, Vesa; Utriainen, Tapio; Luukkaa, Marjaana; Leskinen, Markku; Pulkkanen, Kalevi; Kautio, Anna-Liisa; Huttunen, Teppo (2020)
    Background/Aim: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. Patients and Methods: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. Results: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. Conclusion: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.
  • Huhtaniemi, Riikka; Sipila, Petra; Junnila, Arttu; Oksala, Riikka; Knuuttila, Matias; Mehmood, Arfa; Aho, Eija; Laajala, Teemu D.; Aittokallio, Tero; Laiho, Asta; Elo, Laura; Ohlsson, Claes; Thulin, Malin Hagberg; Kallio, Pekka; Makela, Sari; Mustonen, Mika V. J.; Poutanen, Matti (2022)
    Antiandrogen treatment resistance is a major clinical concern in castration-resistant prostate cancer (CRPC) treatment. Using xenografts of VCaP cells we showed that growth of antiandrogen resistant CRPC tumors were characterized by a higher intratumor dihydrotestosterone (DHT) concentration than that of treatment responsive tumors. Furthermore, the slow tumor growth after adrenalectomy was associated with a low intratumor DHT concentration. Reactivation of androgen signaling in enzalutamide-resistant tumors was further shown by the expression of several androgen-dependent genes. The data indicate that intratumor DHT concentration and expression of several androgen-dependent genes in CRPC lesions is an indication of enzalutamide treatment resistance and an indication of the need for further androgen blockade. The presence of an androgen synthesis, independent of CYP17A1 activity, has been shown to exist in prostate cancer cells, and thus, novel androgen synthesis inhibitors are needed for the treatment of enzalutamide-resistant CRPC tumors that do not respond to abiraterone.
  • Peltola, Katriina J.; Bono, Petri; Hugh Jones, Robert; Vjaters, Egils; Nykänen, Pirjo; Vuorela, Annamari; Oksala, Riikka; Pohjanjousi, Pasi; Mustonen , Mika V. J.; Fizazi, Karim; Massard, Christophe (2020)
    Background: Most prostate cancer patients develop castration-resistant prostate cancer (CRPC) after androgen deprivation therapy treatment. CRPC growth is mediated mostly by androgen receptor signalling driven by primary androgens synthesised largely by the CYP17A1 enzyme. Objective: To evaluate the safety profile and dose-limiting toxicities of ODM-204. Design, setting, and participants: In this open, uncontrolled, nonrandomised, multi-centre, tolerability and pharmacokinetic first-in-man phase I dose escalation study, patients with metastatic CRPC were randomised to receive ODM-204 in sequential cohorts of five dose levels (ie, 50, 100, 200, 300, and 500 mg twice daily) concomitantly with prednisone. Intervention: ODM-204, a novel, orally administered, investigational, nonsteroidal dual inhibitor of CYP17A1 and androgen receptor. Outcome measurements and statistical analysis: ODM-204 plasma concentrations, serum testosterone, and prostate-specific antigen (PSA) levels were evaluated and imaging of lesions was performed. Results and limitations: Of the 23 patients enrolled into the study, 60.9% experienced mild adverse effects considered to be related to the study treatment, which were fatigue, increased/decreased appetite, nausea, asthenia, diarrhoea, and weight decrease. ODM-204 area under the curve (AUC(0-12)) values increased dose dependently until the 300 mg dose. The AUC was lower on day 8 after repeated dosing compared with day 1 from the 200 mg dose upwards. Decreases in testosterone levels were seen with ODM-204 treatment confirming androgen deprivation. Of the patients, 13% also demonstrated a >50% decrease in PSA at week 12 and continued ODM-204 treatment for over a year. Conclusions: ODM-204 was well tolerated up to the highest evaluated dose. There were decreases in both testosterone and PSA levels, suggesting preliminary antitumour activity in the treatment of CRPC. The pharmacokinetic properties of the molecule, however, prevent further development. Patient summary: This study looked at the safety of ODM-204, a novel dual inhibitor of CYP17A1 and the androgen receptor, in castration-resistant prostate cancer patients. ODM-204 treatment was found to be well tolerated, and it also reduced both serum testosterone and prostate-specific antigen levels, but the properties of the molecule prevent further development. (C) 2018 European Association of Urology. Published by Elsevier B.V.