scholarly journals Preliminary phase I data on the feasibility of administering twice-a-week paclitaxel and definitive radiation therapy for androgen-ablated locally advanced prostate cancer

2001 ◽  
Vol 51 (3) ◽  
pp. 301-302
Author(s):  
B.E. Ellerin ◽  
A. Chachoua ◽  
S. Taneja ◽  
M. Saboori ◽  
K. DeWyngaert ◽  
...  
BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e038678
Author(s):  
Yu-Tian Xiao ◽  
Xianzhi Zhao ◽  
Yifan Chang ◽  
Xiaojun Lu ◽  
Ye Wang ◽  
...  

IntroductionPatients with locally advanced prostate cancer are at high risk of recurrence after definitive treatment. There are emerging data that radical prostatectomy can delay the progression of castration resistance and potentially prolong survival. Neoadjuvant radiation therapy improves local control and has shown survival benefit with favourable toxicity profiles in several other malignancies. We have designed this trial to investigate whether this combination, which theoretically maximises local control, is a safe and feasible approach for treating locally advanced prostate cancer.Methods and analysisThis study is a phase I, open-label study to investigate the safety and feasibility of neoadjuvant hormone and radiation therapy followed by robot-assisted radical prostatectomy by a traditional 3+3 dose-escalation design with four planned radiation dose levels (39.6 Gy/22F, 45 Gy/25F, 50.4 Gy/28F and 54 Gy/30F). Locally advanced prostate cancer patients with positive pelvic and/or retroperitoneal lymph nodes will be recruited. The primary objective is to determine the adverse events and maximal tolerable dose (MTD) of neoadjuvant radiotherapy. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.5.0.Ethics and disseminationThis protocol was approved by the Institutional Review Board of Shanghai Changhai Hospital (ref. CHEC2019-070 and CHEC2019-082). The study will be performed in compliance with applicable local legislation and in accordance with the ethical principles developed by the World Medical Association in the Declaration of Helsinki 2013. Study results will be disseminated through conferences and peer-reviewed scientific journals.Trial registration numbersChiCTR1900022716; ChiCTR1900022754.


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Akira Kazama ◽  
Toshihiro Saito ◽  
Keisuke Takeda ◽  
Kazuhiro Kobayashi ◽  
Toshiki Tanikawa ◽  
...  

Background. To predict long-term treatment outcome of radiation therapy (RT) plus androgen deprivation therapy (ADT) for high-risk locally advanced prostate cancer. Methods. In total, 204 patients with the National Comprehensive Cancer Network (NCCN) high risk locally advanced prostate cancer (PSA > 20 ng/ml, Gleason score ≧ 8, clinical T stage ≧ 3a) were treated with definitive RT with ADT. Median follow up period was 113 months (IQR: 95–128). Median neoadjuvant ADT and total ADT duration were 7 months (IQR: 6–10) and 27 months (IQR: 14–38), respectively. Results. PSA recurrence-free survival (PSA-RFS), cancer specific survival (CSS), and overall survival (OS) rates at 5 years were 84.1%, 98.5%, and 93.6%, respectively, and 67.9%, 91.2%, and 78.1%, respectively, at 10 years. Pre-RT PSA less than 0.2 ng/ml was associated with superior outcomes of PSA-RFS (HR = 0.42, 95% CI: 0.25–0.70, p=0.001), CSS (HR = 0.27, 95% CI: 0.09–0.82, p=0.013), and OS (HR = 0.48, 95% CI: 0.26–0.91, p=0.021). On multivariate analysis, age (≥70 y.o.) and pre-RT PSA (≥0.2 ng/ml) were factors predictive of poorer OS (p=0.032) , but iPSA, T stage, Gleason score, number of NCCN high-risk criteria, a combination with anti-androgen therapy and neoadjuvant ADT duration were not predictive of treatment outcome. Conclusion. In patient with high-risk prostate cancer, RT plus ADT achieved good oncologic outcomes. PSA < 0.2 ng/ml before radiation therapy is a strong independent predictor for long overall survival.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 150-150 ◽  
Author(s):  
David Azria ◽  
Xavier Rebillard ◽  
Nathalie Coux ◽  
Marta Jarlier ◽  
Rodolphe Thuret ◽  
...  

150 Background: Everolimus is able to stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving everolimus together with hormonotherapy and radiation therapy may kill more tumor cells. Methods: We conducted a phase I trial to evaluate the impact of everolimus (RAD001), an mTOR inhibitor, in patients treated concurrently with radiotherapy (RT) and ablative androgen treatment in high-risk locally advanced prostate cancer. Inclusion criteria were high-risk locally advanced non metastatic prostate cancer defined as clinical stage ≥ T3 or Gleason score ≥ 8 or PSA ≥ 20. The week before the beginning of RT, RAD001 was administered at different dose levels, twice daily, until the last day of irradiation. A nonsteroid antiandrogen was also given for 1 month at the beginning of RT. Prostate and seminal vesicle were irradiated up to 74Gy in 37 fractions of 2Gy with concomitant long-term LHRH analogue. The starting dose of RAD001 was 5mg/d with subsequent dose levels of 7.5 and 10 mg/d. The primary endpoint was the determination of the maximum tolerated dose (MTD). Dose escalation was implemented according to the continual reassessment method (CRM). Results: Fifteen patients were enrolled and 14 were assessable for toxicity and response. Significant toxicities were demonstrated at the 7.5 and 10 mg/d dose levels. Dose-limiting toxicity (DLT) occurred in two patients at dose level 7.5 mg/d and characterized by a grade 3 diarrhea and a grade 3 hydronephrosis due to dehydration and kidney lithiasis. DLT also occurred in two patients at dose level 10 mg/d (grade 3 diarrhea and grade 3 laryngopharyngeal infection). The MTD was reached at 7.5 mg/day (dose-level II). The recommended dose of RAD001 was 5 mg/d. After a median follow-up of 22 months, 12 patients are alive, 1 is dead (not related to cancer) and 2 patients had relapsed. Conclusions: Concomitant hormone-radiotherapy and everolimus is well-tolerated with mucositis, hypercholesterolemia, and urinary disorders. The recommended phase-II trial dose of everolimus in this combined setting is 5 mg/day. Clinical trial information: NCT00943956.


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