The Pharmacology &Experimental Therapeutics (PET) Section focuses on the selection and clinical development of new anticancer drugs for the treatment of childhood cancers, neurofibromatosis (led by Dr. Brigitte Widemann) and cancers that occur in children with genetic cancer predisposition syndromes (Dr. Widemann). The Section has an active clinical trials program to study the toxicity, activity, pharmacokinetics and pharmacodynamics of these agents in children. Clinical trials are performed as single institution studies or collaboratively with other children's cancer centers or cooperative groups. A variety of agents are studied, including molecularly targeted drugs such as vandetanib and R1507, cytotoxic drugs such as trabectedin, antiangiogenic agents such as cediranib, monoclonal antibodies and drugs that modulate the therapeutic or toxic effects of anticancer drugs such as olaparib, talabostat and tariquidar. The Section works with the Cancer Therapy Evaluation Program and the pharmaceutical industry to ensure that promising new drugs are studied in children. The Section is a non-funded member of the COG Phase1/Pilot Consortium and COG. This has allowed the movement of agents studied in phase I trials in the Section (e.g., ABT-751, ixabepilone) into phase II trials in the cooperative groups. For example, the phase I trial of ABT-751 led by Dr. Elizabeth Fox evaluated two dosing schedules and enrolled a total of 76 patients, including 50 patients with neuroblastoma. The preliminary data suggesting that the drug had clinical activity in neuroblastoma resulted in a COG phase 2 trial in this disease also led by Dr. Fox. This study has enrolled patients ahead of schedule and is close to completion. The Section has also opened a novel phase 1/2 trial of vandetanib in children with MEN and medullary thyroid carcinoma. This is the first trial to include an extramural investigator (Dr. Sam Wells) as an adjuvant PI, and it has accrued patients from around the world, primarily with MEN 2B. Overall, vandetanib has been well tolerated and most patients enrolled on this trial have experienced tumor shrinkage during treatment with vandetanib. The Section has a collaborative initiative to manufacture a drug development tissue microarray to aid in selecting the new molecularly targeted drugs that are best suited for development in childhood cancers.
