Toxicity in patients receiving adjuvant docetaxel + hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer: a preplanned safety report of the SPCG-13 trial

Abstract

and for the SPCG-13 BACKGROUND: Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate-or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS:The inclusion criteria are the following: men 418 and p75 years of age, WHO/ECOG performance status 0--1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4 þ 3), PSA 410; T2, Gleason 8--10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m À2 d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3--4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3--4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.

ANO7 rs77559646 Is Associated With First-line Docetaxel Treatment Response in Metastatic Castration-resistant Prostate Cancer

“…The current analysis is the first study reporting a single germline variant associated with aggressive PCa and with outcome of mCRPC after docetaxel treatment. This is an especially important finding taking into account the possible adjuvant use of docetaxel in high-risk PCa (21)(22)(23). Moreover, ANO7 is not a DNA-repair gene, therefore revealing there must be another pathway underlying the response to docetaxel.…”

Cytotoxic chemotherapy in the contemporary management of metastatic castration‐resistant prostate cancer (mCRPC)

“…The sponsor stopped the study early, and data are currently being collected and analysed through a multi‐institutional registry (NCT01813370). The Scandinavian Prostate Cancer Group (SPCG) 15 study of adjuvant docetaxel after radiotherapy reported high rates of neutropenia . A similar study, Prostate Cancer Consortium in Europe (PEACE) 2 (NCT01952223), will assess cabazitaxel plus pelvic radiotherapy in patients with high‐risk localised prostate cancer.…”

A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer

“…Standard chemotherapies, while effectively killing cancer cells, also result in adverse side effects 44,45 . Encapsulation of cytotoxic agents in micro/nanoparticles has emerged over the last two decades as a promising approach to overcome some of the challenges in systemic delivery of such therapeutics 9,46 .…”