This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Irinotecan is a semisynthetic water soluble analog of camptothecin that differs from other camptothecin analogs, such as topotecan and 9-aminocamptothecin, in that it is a prodrug that undergoes deesterification to a much more potent topoisomerase-I inhibitor, SN-38. Similar to other camptothecin analogs, both irinotecan and its active metabolite, SN-38, undergo pH-dependent reversible hydrolysis from active lactone species to hydroxy acid (carboxylate) forms. Irinotecan itself possesses a marginal antiproliferative effect, while its metabolite SN-38 is 100-fold more active in vitro. Irinotecan has demonstrated significant preclinical as well as clinical antitumor activity. A high degree of activity including cures have been observed in a broad spectrum of murine tumors including Ehrlich carcinoma, MH134 hepatoma, S180, and meth A fibrosarcoma. Significant antitumor activity has also been reported in xenografts derived from pediatric tumors such as neuroblastoma and rhabdomyosarcoma, as well as in rhabdomyosarcoma xenografts selected in vivo for resistance to vincristine, melphalan and topotecan. In addition, significant activity against a variety of xenografts derived from adult tumors including colon adenocarcinoma Co-4, mammary carcinoma MX-1, gastric adenocarcinomas ST-15 and SC-6, squamous cell carcinoma QG-56, and lung tumor xenografts Mqnul, Msnul, and LX1 has been observed. Finally, significant objective clinical activity has recently been reported in both Phase I and Phase II clinical trials of irinotecan in adult patients. The objectives of this study are: 1) To estimate the maximum tolerated and dose-limiting toxicities of irinotecan administered over 90 min, weekly x 4, every 6 weeks in children with refractory or progressive solid tumors; 2) To determine the pharmacokinetics of irinotecan and its active metabolite SN-38 administered over 90 min, weekly x 4, every 6 weeks to children with refractory or progressive cance; and 3) To determine the pharmacokinetics of irinotecan and its active metabolite SN-38 administered weekly x 4, every 6 weeks to children with refractory or progressive cancer who are receiving concomitant anticonvulsants.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000188-42
Application #
7374926
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2005-12-01
Project End
2006-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
42
Fiscal Year
2006
Total Cost
$2,171
Indirect Cost
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Hunsaker, Sanita L; Garland, Beth H; Rofey, Dana et al. (2018) A Multisite 2-Year Follow Up of Psychopathology Prevalence, Predictors, and Correlates Among Adolescents Who Did or Did Not Undergo Weight Loss Surgery. J Adolesc Health 63:142-150
Lanzieri, Tatiana M; Chung, Winnie; Leung, Jessica et al. (2018) Hearing Trajectory in Children with Congenital Cytomegalovirus Infection. Otolaryngol Head Neck Surg 158:736-744
Bollard, Catherine M; Tripic, Tamara; Cruz, Conrad Russell et al. (2018) Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma. J Clin Oncol 36:1128-1139
Michalsky, Marc P; Inge, Thomas H; Jenkins, Todd M et al. (2018) Cardiovascular Risk Factors After Adolescent Bariatric Surgery. Pediatrics 141:
Lau, Chantal (2018) Breastfeeding Challenges and the Preterm Mother-Infant Dyad: A Conceptual Model. Breastfeed Med 13:8-17
Gururangan, Sridharan; Reap, Elizabeth; Schmittling, Robert et al. (2017) Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11). Cancer Immunol Immunother 66:1589-1595
Lanzieri, T M; Leung, J; Caviness, A C et al. (2017) Long-term outcomes of children with symptomatic congenital cytomegalovirus disease. J Perinatol 37:875-880
El-Hattab, Ayman W; Zarante, Ana Maria; Almannai, Mohammed et al. (2017) Therapies for mitochondrial diseases and current clinical trials. Mol Genet Metab 122:1-9
Jin, Haoxing Douglas; Demmler-Harrison, Gail J; Coats, David K et al. (2017) Long-term Visual and Ocular Sequelae in Patients With Congenital Cytomegalovirus Infection. Pediatr Infect Dis J 36:877-882
Oh, Sam S; Du, Randal; Zeiger, Andrew M et al. (2017) Breastfeeding associated with higher lung function in African American youths with asthma. J Asthma 54:856-865

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