2010
DOI: 10.1634/theoncologist.2009-0117
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Combining Targeted Therapies: Practical Issues to Consider at the Bench and Bedside

Abstract: Numerous practical issues must be considered when combining targeted therapies in early clinical drug development. These include tumor resistance mechanisms, the existence of multiple, redundant signaling pathways, and the failure of single-agent therapies to achieve cures. The strategies adopted to examine combinatorial therapy include the goal of hitting more than one target by specifically inhibiting signal transduction cascades and suppressing specific mechanisms of action with the use of multitargeted kin… Show more

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Cited by 43 publications
(44 citation statements)
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“…The low rate of failure to enroll because of ineligibility is of interest. It has been well documented that there has been a rapid rise in eligibility criteria for phase I trials (31). The low rate of ineligibility and high enrollment rate might be the result of several factors: (1) high rate of referral of patients from within MD Anderson, a tertiary care center where physicians were familiar with phase I trials; (2) presence of a nurse in the business office who prescreened patients referred from other institutions using a simple but effective questionnaire to ensure that patients who were too ill and/or who had insufficient financial support understood that a phase I trial was unlikely to be an appropriate option; (3) the availability of a large menu of phase I trials (n ϭ 128 in 2012) so that openings were available on multiple trials; (4) a high number of investigator-driven trials (about 50% of open trials) with relaxed eligibility criteria; (5) pre-referral discussion with patients regarding the requirements and intensity of phase I trials as a routine of practice; (6) social service personnel who assisted patients with appropriate hotel and travel recommendations; (7) the presence in the clinic of experienced doctors of pharmacy who were knowledgeable about drug interactions that could affect eligibility; (8) dedicated phase I physicians who had the time and experience to enroll and manage patients on trials; and (9) well-trained research nurses and study coordinators who were able to recognize and resolve enrollment barriers and delays.…”
Section: Discussionmentioning
confidence: 99%
“…The low rate of failure to enroll because of ineligibility is of interest. It has been well documented that there has been a rapid rise in eligibility criteria for phase I trials (31). The low rate of ineligibility and high enrollment rate might be the result of several factors: (1) high rate of referral of patients from within MD Anderson, a tertiary care center where physicians were familiar with phase I trials; (2) presence of a nurse in the business office who prescreened patients referred from other institutions using a simple but effective questionnaire to ensure that patients who were too ill and/or who had insufficient financial support understood that a phase I trial was unlikely to be an appropriate option; (3) the availability of a large menu of phase I trials (n ϭ 128 in 2012) so that openings were available on multiple trials; (4) a high number of investigator-driven trials (about 50% of open trials) with relaxed eligibility criteria; (5) pre-referral discussion with patients regarding the requirements and intensity of phase I trials as a routine of practice; (6) social service personnel who assisted patients with appropriate hotel and travel recommendations; (7) the presence in the clinic of experienced doctors of pharmacy who were knowledgeable about drug interactions that could affect eligibility; (8) dedicated phase I physicians who had the time and experience to enroll and manage patients on trials; and (9) well-trained research nurses and study coordinators who were able to recognize and resolve enrollment barriers and delays.…”
Section: Discussionmentioning
confidence: 99%
“…The essential relationships between the internal and external factors and the regularities are reflected using such thinking modes as concept, judgment, reasoning, etc. [22]. Based on the long-term medical practical activities, Mongolian medicine uses the ancient philosophical thoughts and methodologies, ancient astronomical, geological, climatic, biological, physical, and psychological knowledge to summarize, analyze, and induce the human organization structure, physiological functions, causes, incidence, pathogenesis, health maintenance, diagnosis and treatment etc.…”
Section: Thinking Mode In Mongolian Medicinementioning
confidence: 99%
“…Strict patient selection will be pivotal in order to obtain maximal clinical advantages. The complexity of drug development, however, particularly when combining targeted therapies will also increase [31]. Clinical investigators will have to break fresh ground and adapt current strategies in early drug development.…”
Section: Futurementioning
confidence: 99%