A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study

2021 ◽  
Vol 47 (1) ◽  
pp. 115-122 ◽  
Author(s):  
S.J. Valle ◽  
J. Akhter ◽  
A.H. Mekkawy ◽  
S. Lodh ◽  
K. Pillai ◽  
...  
Author(s):  
Jafari Mehraneh D ◽  
Carmichael Joseph C ◽  
Dayyani Farshid ◽  
McKinney Chelsea ◽  
Wenzel Lari ◽  
...  

2017 ◽  
Vol 27 (11) ◽  
pp. 3447-3459 ◽  
Author(s):  
Kristen M Cunanan ◽  
Joseph S Koopmeiners

The primary goal of a phase I clinical trial in oncology is to evaluate the safety of a novel treatment and identify the maximum tolerated dose, defined as the maximum dose with a toxicity rate below some pre-specified threshold. Researchers are often interested in evaluating the performance of a novel treatment in multiple patient populations, which may require multiple phase I trials if the treatment is to be used with background standard-of-care that varies by population. An alternate approach is to run parallel trials but combine the data through a hierarchical model that allows for a different maximum tolerated dose in each population but shares information across populations to achieve a more accurate estimate of the maximum tolerated dose. In this manuscript, we discuss hierarchical extensions of three commonly used models for the dose–toxicity relationship in phase I oncology trials. We then propose three dose-finding guidelines for phase I oncology trials using hierarchical modeling. The proposed guidelines allow us to fully realize the benefits of hierarchical modeling while achieving a similar toxicity profile to standard phase I designs. Finally, we evaluate the operating characteristics of a phase I clinical trial using the proposed hierarchical models and dose-finding guidelines by simulation. Our simulation results suggest that incorporating hierarchical modeling in phase I dose-escalation studies will increase the probability of correctly identifying the maximum tolerated dose and the number of patients treated at the maximum tolerated dose, while decreasing the rate of dose-limiting toxicities and number of patients treated above the maximum tolerated dose, in most cases.


2004 ◽  
Vol 50 (8) ◽  
pp. 2580-2589 ◽  
Author(s):  
R. John Looney ◽  
Jennifer H. Anolik ◽  
Debbie Campbell ◽  
Raymond E. Felgar ◽  
Faith Young ◽  
...  

2020 ◽  
Vol 29 (4) ◽  
pp. 2109-2130
Author(s):  
Lauren Bislick

Purpose This study continued Phase I investigation of a modified Phonomotor Treatment (PMT) Program on motor planning in two individuals with apraxia of speech (AOS) and aphasia and, with support from prior work, refined Phase I methodology for treatment intensity and duration, a measure of communicative participation, and the use of effect size benchmarks specific to AOS. Method A single-case experimental design with multiple baselines across behaviors and participants was used to examine acquisition, generalization, and maintenance of treatment effects 8–10 weeks posttreatment. Treatment was distributed 3 days a week, and duration of treatment was specific to each participant (criterion based). Experimental stimuli consisted of target sounds or clusters embedded nonwords and real words, specific to each participants' deficit. Results Findings show improved repetition accuracy for targets in trained nonwords, generalization to targets in untrained nonwords and real words, and maintenance of treatment effects at 10 weeks posttreatment for one participant and more variable outcomes for the other participant. Conclusions Results indicate that a modified version of PMT can promote generalization and maintenance of treatment gains for trained speech targets via a multimodal approach emphasizing repeated exposure and practice. While these results are promising, the frequent co-occurrence of AOS and aphasia warrants a treatment that addresses both motor planning and linguistic deficits. Thus, the application of traditional PMT with participant-specific modifications for AOS embedded into the treatment program may be a more effective approach. Future work will continue to examine and maximize improvements in motor planning, while also treating anomia in aphasia.


2007 ◽  
Vol 177 (4S) ◽  
pp. 202-202
Author(s):  
Hirotsugu Uemura ◽  
Motoyoshi Tanaka ◽  
Shigeya Uejima ◽  
Takafumi Minami ◽  
Kiyohide Fujimoto ◽  
...  

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