Safety, tolerability, pharmacokinetic and escalating single doses of PCK3145 in patients with metastatic hormone resistant prostatic cancer (HRPC)
Notice bibliographique
Résumé
4473 Introduction and Objective: Prostate secretory protein (PSP94) within PSA and PAP is one of the three most abundant protein in the seminal fluid. PSP94 has demonstrated antiproliferative and anti-tumour activity both in vitro and in vivo animal models. PCK3145 is a synthetic 15-mer peptide that matches the natural sequence of amino acids 31 to 45 of the prostate secretory protein (PSP94) and has demonstrated similar antiproliferative and antitumoral activity in the animal models PC3 and the Dunning rat R-3327 MLL. The mechanism of action of PCK3145 is not fully elucidated but may be related in part to induction of apoptosis. The primary objective of this clinical study was to evaluate the safety and the tolerability of PCK3145 administered i.v. over a range of potentially therapeutic doses. The secondary objectives were to determine the pharmacokinetic profile and to evaluate efficacy data using tumour assessments and tumour markers. Methods: Since October 2002, 12 metastatic Hormone Resistant Prostatic Cancer (HRPC) patients have been receiving treatment in this open-label, non-randomized, dose-escalation study in which successive cohorts of at least 4 patients are receiving 4 ascending doses (5, 20, 40 and 80 mg/m2) of PCK3145 (33-day cycle of treatment consisting of PCK3145 administration three times per week for 26 days, followed by a 7-day Post-Treatment Observation Period). The dose escalation is based on dose-limiting toxicity (DLT). Results: Preliminary characteristics (n = 8) are that the median age is 67 y (53-75) and the median time from HRPC to enrolment is 12.5 months (0.7-34). The Karnofsky Performance Status, remained high. The majority of the patients received hormonal therapy, had radiotherapy and TURP (Transurethral Prostatectomy). Sites of disease were mainly bone and lymph node. Serious Adverse Events (SAEs) reported so far are all unlikely or unrelated to study drug. Preliminary results indicate that the half-life of PCK3145 is 20 minutes and tumor assessments suggest that the patients are having stable disease at least after one cycle. Some patients showed a decline in PSA levels (one of them by almost 50%). All patients who had plasma MMP-9 levels over 100 ug/L before treatment had reductions ranging from 34% to 90% after two cycles of treatment. In the other patients that had low levels of MMP-9 prior to treatment, they remained low and only increased in two cases when cancer relapse was deemed to have occurred. Conclusions: These clinical results are very interesting and suggest the potential role of PCK3145 in the intervention of the metastatic process. The marked reduction in plasma MMP-9 levels of patients receiving PCK3145 treatment clearly indicates a biochemical effect, and provides a potentially novel mechanism of action of this small molecule in these patients.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».