The Pharmacology & Experimental Therapeutics (PET) Section focuses on the selection and clinical development of new agents for the treatment of childhood cancers and of genetic tumor predisposition syndromes such as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and medullary thyroid carcinoma. The PET Section uses an integrated research program that includes preclinical models to study the pharmacology and applications of new agents in childhood tumors and an active clinical trials program to study the toxicity, activity, pharmacokinetics and pharmacodynamics of these agents in children and young adults. In collaboration with the Pediatric Neuro-Oncology Section, the central nervous system pharmacology of anticancer drugs is also studied because of the high incidence of primary and metastatic central nervous system cancers in children. Clinical trials are developed with an emphasis on new trial designs and endpoints, and are performed as single institution studies or collaboratively with other children's cancer centers or cooperative groups.
A variety of agents are studied including cytotoxic drugs, molecularly targeted drugs, antiangiogenic agents, and drugs that modulate the therapeutic or toxic effects of anticancer drugs. The PET Section works with the Cancer Therapy Evaluation Program (CTEP) and the pharmaceutical industry to ensure that promising new drugs are studied in children. Dr. Widemann serves as the NCI Pediatric Oncology Branch Principal Investigator of the Children’s Oncology Group Phase I Consortium and the Department of Defense sponsored Neurofibromatosis Consortium. Clinical trials performed through the consortia are thus available to patients referred to the POB for clinical trials.
In addition to the conduct of early clinical trials for children and young adults with refractory cancers, the PET Section has established a program for NF1 related tumor and non-tumor manifestations. Phase I and II trials for NF1 related plexiform neurofibromas, which cannot be easily resected, and for patients with NF1 associated and sporadic malignant peripheral nerve sheath tumors (MPNST) are conducted. In addition to treatment trials, a longitudinal natural history trial for children and young adults with NF1 is open for enrollment. On this study, individuals with NF1 are followed longitudinally for their tumor and non-tumor manifestations. A better understanding of the natural history of NF1 will be helpful for the development of clinical trial designs and outcome measurements to explore novel and effective treatments for the many tumor and non-tumor manifestations of NF-1.
The PET Section uses novel approaches for image analysis of tumors in patients with NF1. The use of volumetric MRI analysis of plexiform neurofibromas was developed at the POB and allows for more sensitive measurements of these complex tumors.
Multiple endocrine neoplasia (MEN) types 2A and 2B are rare genetic diseases, which lead to the development of medullary thyroid cancer, usually in childhood. Surgery is the only standard treatment. Patients with medullary thyroid cancer can be cured only by thyroidectomy, but only when it is performed at a time when the tumor is confined to the thyroid gland. Traditional chemotherapy is not effective in this cancer. The PET Section has developed a clinical trial with the targeted agent vandetanib for children and young adults with medullary thyroid carcinoma and is currently ongoing.