A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials
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| Language: | English |
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University of Cincinnati / OhioLINK
2012
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=ucin1330023465 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-ucin13300234652021-08-03T06:15:19Z A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials Dorris, Kathleen Surgery pediatric oncology solid tumor molecularly targeted drugs developmental therapeutics Background: Prior reviews of phase I pediatric oncology trials involving primarily cytotoxic agents have reported objective response rates (ORR) and toxic death rates (TDR) of 7.9-9.6% and 0.5%, respectively. These data may not reflect safety and efficacy in phase I trials of molecularly targeted drugs, which are usually cytostatic. Methods: A systematic review of pediatric phase I oncology trials in patients with refractory solid tumors published from 1990 to 2010 was performed. Publications were identified through a PubMed query for “phase I,” “pediatric” and “cancer” search terms. The published reports were evaluated for patient characteristics, toxicity information and response numbers. Results: Eighty-nine phase I pediatric solid tumor clinical trials enrolling 2623 children were identified. Thirty trials investigated 26 molecularly targeted drugs; 59 trials evaluated 37 cytotoxic agents. A meta-analysis demonstrated that the ORR is significantly higher with cytotoxic drugs (0.068 vs 0.026 per study subject; p<0.001). On the contrary, the pooled estimate of the SDR is similar for cytotoxic versus molecularly targeted drugs (0.201 vs. 0.211 per study subject; p=0.796). The pooled estimate of the DLT rate is higher with cytotoxic drugs (0.3229 vs 0.2402 per study subject; p=0.0807, marginally significant). The hematologic grade 3-4 toxicity episode rate is significantly higher with cytotoxic drugs (0.4798 vs. 0.2043 per course of therapy; p=0.0035); however, the overall and non-hematologic grade 3-4 toxicities occur at similar rates for cytotoxic and molecularly targeted drugs. Conclusions: In phase I pediatric solid tumor trials, ORR were significantly higher for cytotoxic versus molecularly targeted agents. SDR were similar in molecularly targeted and cytotoxic drug trials. Although TDR were similar in both groups, patients treated with cytotoxic agents were more likely to experience a DLT or hematologic grade 3-4 toxicity than those patients receiving molecularly targeted drugs. These observations should help to guide future phase I/II pediatric oncology clinical trial designs for novel molecularly targeted drugs. 2012-04-19 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1330023465 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1330023465 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Surgery pediatric oncology solid tumor molecularly targeted drugs developmental therapeutics |
| spellingShingle |
Surgery pediatric oncology solid tumor molecularly targeted drugs developmental therapeutics Dorris, Kathleen A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials |
| author |
Dorris, Kathleen |
| author_facet |
Dorris, Kathleen |
| author_sort |
Dorris, Kathleen |
| title |
A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials |
| title_short |
A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials |
| title_full |
A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials |
| title_fullStr |
A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials |
| title_full_unstemmed |
A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials |
| title_sort |
comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase i solid tumor oncology trials |
| publisher |
University of Cincinnati / OhioLINK |
| publishDate |
2012 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1330023465 |
| work_keys_str_mv |
AT dorriskathleen acomparisonofsafetyandefficacyofcytotoxicversusmolecularlytargetedagentsinpediatricphaseisolidtumoroncologytrials AT dorriskathleen comparisonofsafetyandefficacyofcytotoxicversusmolecularlytargetedagentsinpediatricphaseisolidtumoroncologytrials |
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