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Chair of Children’s Oncology Group (COG) discusses career, drug development

Host Dr Tim Cripe of  ”This Week in Pediatric Oncology” podcast interviews Dr Peter Adamson, new COG Chair. Co-hosts for this episode are Dr Jim Geller, Dr Raj Nagarajan, and Dr Lionel Chow. This conversation includes Dr Adamson’s background and interest in pediatric oncology, and openly addresses the much-needed advances in drug development for pediatric tumors that are distinct from adult tumors.  On the heels of the remarkable ch14.18 development story in neuroblastoma, Dr Adamson explains the need for a “virtual” drug company that consists of a public-private partnership to develop drugs in a similar narrow venue, which is underway.

Reference:

Making Better Drugs for Children with Cancer. Institute of Medicine Consensus Report. Peter C. Adamson, Susan L. Weiner, Joseph V. Simone, and Hellen Gelband, Editors. April 18, 2005

Background:

Dr Adamson was elected by principal investigators of more than 200 Children’s Oncology Group sites. COG includes more than 5,000 experts in childhood cancer at leading children’s hospitals, universities and cancer centers across North America, Australia, New Zealand and Europe.

In 1999 Dr. Adamson came to The Children’s Hospital of Philadelphia (CHOP) from the National Cancer Institute (NCI), and is the director of Clinical and Translational Research and chief of the Division of Clinical Pharmacology and Therapeutics at Children’s Hospital. He also is a professor of Pediatrics and Pharmacology at the University of Pennsylvania School of Medicine. He remains on the staff of Children’s Hospital and on the Penn faculty while serving as Children’s Oncology Group chair.

Dr. Adamson’s previous roles at COG include leading the 21-site phase 1 consortium. During the eight years that Dr. Adamson led this effort, the collaborating sites conducted more than 25 studies designed to test the safety of novel anticancer drugs.

Says Dr Adamson, “I hope to fully leverage the emerging discoveries being made at a rapid pace by transforming how research moves from the bench to the bedside in a very large collaboration.”

Dr. Adamson received his MD from Cornell University and completed his residency at CHOP in 1987. He then spent 10 years at the NCI where he finished his fellowship in Pediatric Hematology/Oncology and Biotechnology, and worked as an investigator and an attending physicians before coming to CHOP.

Please send questions or comments to twipo@solvingkidscancer.org

July 23, 2011 ~ Neuroblastoma Children’s Cancer Alliance (NCCA) Parent Meeting in Central London, UK

An open meeting for parents to meet and discuss NB topics. Donna Ludwinski will present history of frontline NB treatment, relapse therapies, and current research in US and Europe. Other speakers TBD. See meeting poster for details: NB Parent Meeting London 23 July 2011

http://www.childrenscancer.org.uk/

http://j-a-c-k.org/

Travel supported by NCCA and J-A-C-K Foundation

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An oncolytic virus for a common childhood brain tumor

In this eighth episode of “This Week in Pediatric Oncology” podcast hosts Dr Tim Cripe, Dr Lars Wagner and Dr Lionel Chow discuss a recent publication by researchers at Baylor/Texas Children’s in Houston that shows remarkable results of Seneca Valley virus SVV-001 on orthotopic mouse models of medulloblastoma.

The TWiPO hosts raise many interesting points about this research and highlight the strengths as well as limitations of this work. This exciting research provides new evidence of promise for oncolytic virus therapy for childhood tumors.

For more information about oncolytic virus trials for pediatric cancers, see a recent webinar “Oncolytic Virotherapy for Pediatric Solid Tumors” presented by the principal investigators of five clinical trials in children and sponsored by Solving Kids’ Cancer.

The article discussed in this episode can be found here:

A single intravenous injection of oncolytic picornavirus SVV-001 eliminates medulloblastomas in primary tumor-based orthotopic xenograft mouse models. Yu L, Baxter PA, et al. Neuro Oncol. 2011 Jan;13(1):14-27. Epub 2010 Nov 12.

Another related article by the same group:

Treatment of invasive retinoblastoma in a murine model using an oncolytic picornavirus. Wadhwa L, Hurwitz MY, et al. Cancer Res. 2007 Nov 15;67(22):10653-6. [fulltext]

Please send questions or comments to twipo@solvingkidscancer.org

Dr Ruth Ladenstein presents data in Plenary Session on randomized trial comparing BuMel vs CEM for transplant after Rapid COJEC induction

Considering that neuroblastoma accounts for 7% of pediatric cancers, and pediatric cancers comprises only 1% of adult cancers (that is .07% of all cancers, and high-risk NB makes up only half that number), it is really quite remarkable when highlighted presentations at ASCO focus on neuroblastoma.  This is on the heels of the ch14.18 results which was also big news at ASCO in 2009.

The European SIOPEN trial accrued 1,577 high-risk children since 2002.  Only 43% of these children were randomized for transplant regimen. The randomization was stopped after review showed superiority of BuMel (busulfan + melphalan) over CEM (carboplatin + etoposide + melphalan) in survival. Toxicity was greater in CEM arm, although more VOD (veno-occlusive disease) was observed in BuMel arm.

Dr Julie Park presented data as discussant comparing outcomes with the COG CEM transplant regimen. Clearly BuMel is better than CEM after Rapid COJEC induction, but a question remains if this would be true for the COG induction, which is very different (21 day schedule vs 10 day schedule which presents a different toxicity profile, higher cisplatin use in SIOPEN and no carboplatin is used in COG induction).

This treatment is now standard in SIOP, and COG is incorporating BuMel in a pilot trial.

For more information, see “Can New Standard of Care in Neuroblastoma Be Used in the US?” by Medscape.

http://abstract.asco.org/AbstView_102_79897.html

Abstract:

Background: The HR-NBL1 trial of the European SIOP Neuroblastoma Group randomised 2 MAT regimens with the primary aim to demonstrate superiority based on event free survival (EFS).

Methods: At randomisation closure, 1,577 high-risk neuroblastoma patients (944 males) had been included since 2002; with INSS stage 4 disease (1,369 pts) > 1 year, infants (65 pts) and stage II and III (143 pts) of any age with MYCN amplification. Response eligibility criteria prior to randomisation after Rapid COJEC Induction (J Clin Oncol, 2010) ± 2 courses of TVD (Cancer, 2003) included complete bone marrow remission and ≤ 3, but improved, mIBG positive spots. The MAT regimens were BuMel (oral busulfan till 2006, 4x150mg/m² in 4 equal doses, or after 2006 intravenous use according to body weight and melphalan 140mg/m²/day) and CEM (carboplatin ctn. infusion [4xAUC 4.1mg/ml.min/day], etoposide ctn. infusion [4x338mg/m²day or 4x200mg/m²/day*], melphalan [3x70mg/m²/day or 3x60mg/m²/day*. *reduced if GFR<100ml/min/1.73m²]). A minimum of 3x10E6 CD34/kgBW PBSC were requested. VOD prophylaxis included ursadiol, but not prophylactic defibrotide. Local control included surgery and radiotherapy of 21 Gy. A total of 598 patients were randomised (296 BuMel, 302 CEM). The median age at randomisation was 3 years (1-17.2) with a median follow up of 3 years.

Results: At the last analysis, the Peto rule of p<0.001 was met. A significant difference in EFS in favour of BuMel (3-years EFS 49% vs 33%) was observed as well as for overall survival (3-years OS 60% vs 48%, p=0.004). This difference was mainly related to the relapse and progression incidence, which was significantly (p<0.001) lower with BuMel (48% vs 60%). The severe toxicity rate up to day 100 (ICU and toxic deaths) was below 10%, but was significantly higher for CEM (p=0.014). The acute toxic death rate was 3% for BuMel and 5% for CEM (NS). The acute MAT toxicity profile favours the BuMel regimen in spite of a total VOD incidence of 18% (grade 3:5%). Based on these results and following advice from the DMC, the randomisation was closed early.

Conclusions: BuMel was demonstrated to be superior to CEM and hence is recommended as standard treatment.

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Advances in Target Discovery and Drug Development in Pediatric Cancers

In this seventh episode of “This Week in Pediatric Oncology” TWiPO podcast, host Dr Tim Cripe interviews Dr E. Anders Kolb and Dr Andrew Napper from Nemours in Wilmington, Delaware.

This informative discussion covers the strategies, scope, and challenges of target discovery, drug development, and preclinical testing for pediatric cancers, a complex process that has been accelerated by high throughput screening technology that has only recently become available in academic settings.

Dr Kolb is the Director of Blood and Bone Marrow Transplantation at Alfred I. duPont Hospital for Children, and Head of the Cancer Therapeutics Laboratory at Nemours Biomedical Research. He is also a Principal Investigator in the Pediatric Preclinical Testing Program (PPTP), a comprehensive program to systematically evaluate new agents against childhood solid tumor and leukemia models.

Dr Andrew Napper joined the research team at the Nemours Center for Childhood Cancer Research (NCCCR) in 2009 to establish its High Throughput Screening and Drug Discovery Laboratory. Dr. Napper came to Nemours from the University of Pennsylvania, where he was the Director of High Throughput Screening for the Penn Center for Molecular Discovery, one of the original ten centers established as part of the National Institutes of Health’s Roadmap initiative to discover drugs for neglected diseases.

For more information on this program and technology:

Lab Offer Hope for Kids with Cancer, Wilmington News Journal (8/24/09)

Academic screening goes high-throughput, Nature Methods 7, 787–792 (2010)

This podcast is sponsored by Solving Kids’ Cancer. Please send questions and comments to twipo@solvingkidscancer.org