Wednesday, November 9, 2011

Novel Cancer Drug Reduces Neuroblastoma Growth By 75 Percent

ScienceDaily (Apr. 23, 2009) — Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have found a new drug that restricts the growth of neuroblastoma, a childhood brain cancer. The pre-clinical study was presented in the plenary session at the 22nd annual meeting of the American Society of Pediatric Hematology/Oncology.

Alejandro Levy, M.D., fellow at the Children's Cancer Hospital at M. D. Anderson, presented research showing for the first time that the M. D. Anderson-developed drug, 3-BrOP, reduces tumor growth by more than 75 percent as a single agent. The study, conducted with human neuroblastoma cells transplanted into mice, showed how 3-BrOP, a glycolysis inhibitor, starved the cancer cells to death by shutting down their main energy source, glucose.

"We found that neuroblastoma cells, unlike healthy cells, are highly dependent on glycolysis for energy instead of more efficient means of energy production," said Levy. "Glycolysis is a process that breaks down sugar for energy, so by blocking that process with 3-BrOP, we are able to keep the tumors from producing energy, and this disrupts their ability to grow."

According to the American Cancer Society, approximately 650 children, mainly under the age of five, are diagnosed with neuroblastoma in the United States each year. Close to two-thirds of these children are diagnosed after the cancer has metastasized to other parts of the body. For these patients with high-risk neuroblastoma, long-term survival is less than 40 percent because the tumors are often resistant to traditional chemotherapy.

Pre-clinically, 3-BrOP has already been proven effective against other cancers including glioblastoma, colon cancer, lymphoma and acute leukemia. A Phase I clinical trial is planned to open this year for adult patients.

"As we explore alternative options to standard chemotherapy agents, we are finding drugs, like 3-BrOP, that have the potential to destroy cancer cells while leaving healthy cells unharmed," said Patrick Zweidler-McKay, M.D., Ph.D., assistant professor at the Children's Cancer Hospital and senior investigator of the study. "These drugs can often enhance the efficacy of other treatments, potentially leading to more successful combinations and better outcomes for our young patients."

Other investigators on the study were Lauren Akers, D.O., Maurizio Ghisoli, M.D., Timothy Graham, Lizhi Zeng, M.D., Riitta Nolo, M.D., Peter Zage, M.D., Ph.D., Wendy Fang, M.D., Sankaranarayanan Kannan, Ph.D., Anna Franklin, M.D., Peng Huang, M.D., Ph.D., and Patrick Zweidler-McKay, M.D., Ph.D.


Friday, November 4, 2011

Neuroblastoma Awareness: Therapy Reduces Dangerous Side-effects of Cancer Treatment in Children

Children given a hormone growth factor alongside chemotherapy for the aggressive cancer neuroblastoma are less likely to suffer a potentially deadly side-effect, according to a major international study published today in the Journal of Clinical Oncology*.

The hormone, called granulocyte colony-stimulating factor (GCSF), was already known to boost production of white blood cells. But this Cancer Research UK-funded study is the first large randomised trial to show it can reduce the complications associated with low white blood cell count in children treated for advanced forms of neuroblastoma.

Around 100 children are diagnosed with neuroblastoma** every year in the UK, usually under the age of five. Overall six out of ten children are successfully treated, but for children with advanced forms of the cancer it is very difficult to treat successfully.

Children diagnosed with advanced forms of neuroblastoma are given particularly intense treatment that combines surgery, radiotherapy and chemotherapy.

But this treatment often carries the side-effect of ‘neutropenia’ - a low white blood cell count. As white blood cells are key components of the immune system, patients who develop neutropenia during treatment are more susceptible to other diseases and complications.

Professor Andy Pearson, lead author of the paper and Cancer Research UK's professor of paediatric oncology at The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust in Sutton, said: “Patients given GCSF immediately after chemotherapy treatment had fewer problems associated with neutropenia, such as fever, infections, days spent in hospital or on antibiotics and gastrointestinal issues.

“Our team previously identified the high dose chemotherapy regimen that is already saving the lives of many children with high risk neurobastoma, and in this study we report finding a new therapy to reduce side-effects for these patients.

“On the strength of these new trial results, all children receiving intense chemotherapy to treat high-risk neuroblastoma will now be given GCSF.”

The work builds on promising results from an earlier study, also funded by Cancer Research UK and led by Professor Pearson at the ICR , which found that giving doses of five chemotherapy drugs – cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide – more frequently offered the best hope of a cure.

This therapy is now being taken forward as the treatment for children in Europe through the International Society of Paediatric Oncology, Europe Neuroblastoma Group (SIOPEN)***.

Kate Law, Cancer Research UK's director of clinical trials, said: "The results of this promising trial mean that children across Europe diagnosed with neuroblastoma will receive a more effective treatment for this disease.

“Cancer Research UK is the largest single funder of children’s cancer research in the country and is at the heart of an international research effort leading to rapid improvements in children surviving cancer with the fewest possible side effects.”


*Ladenstein et al., Journal of Clinical Oncology (2010), Randomised trial of prophylactic granulocyte colony stimulating factor during rapid COJEC induction in paediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study.

** Neuroblastoma is a form of childhood cancer which starts in the child's developing nerves and often appears as a tumour in the abdomen, adrenal glands or the nerve tissue at the back of the abdomen. About one hundred children are diagnosed in the UK each year, mostly before the age of five, and the high-risk form of the disease is one of the main causes of cancer-related deaths in children.

*** The SIOPEN Group led by Dr Ruth Ladenstein at St Anna Children’s Hospital in Vienna, Austria and Professor Pearson at the ICR carried out a Cancer Research UK-funded trial in 16 European countries that assessed the clinical benefit of prophylactic GCSF use. The scientists monitored side-effects of rapid, intense chemotherapy in 119 patients who were routinely given GCSF with 120 patients who were only given GCSF if a severe infection developed.


Neuroblastoma Awareness: Kids with cancer get innovative treatments at new clinic funded by gift to DeVos Children's Hospital

GRAND RAPIDS -- For 8-year-old Ryan Regan, the checkup at the cancer clinic at DeVos Children's Hospital was fun and games.

He laughed when the doctor tickled his belly, showed off a photo of himself in a Superman costume and wandered down the hall to play with friends.

His mother, Cathy Regan, was amazed at how far he had come since he began treatment for neuroblastoma at a pediatric cancer clinic at Helen DeVos Children's Hospital.

"It's a little miracle," said Regan, who lives in Macomb Township in Southeast Michigan.

A grant announced today (Thursday) will provide funding that will allow the clinic to treat more children like Ryan.

The donation of an undisclosed amount of money from Dick and Ethie Haworth establishes the Haworth Family Pediatric Oncology Innovative Therapeutics Clinic, which uses a personalized medicine approach to treating neuroblastoma and other childhood cancers. The director of the clinic, Dr. Giselle Sholler, is also a researcher at Van Andel Institute.

Through the clinic and the institute, the genetic makeup of tumors is analyzed in an effort to determine the best medications to block the cancer. Doctors and researchers in an 11-hospital research consortium are involved in analyzing the test results and choosing the treatment.

Regan said she brought Ryan to the DeVos Children's clinic after doctors at Memorial Sloan-Kettering Cancer Center in New York said they had no more treatment options for him.

Based on the analysis of Ryan's tumor, which formed in his belly and has spread to his liver, Sholler began treating him with three chemotherapy drugs in mid-September. At that point, Ryan weighed only 36 pounds.

"He couldn't walk," his mother said. "He was vomiting. You couldn't pick him up, his liver was so distended. He was on pain meds around the clock."

Ryan's condition improved after the first treatment. In six weeks, he has gained eight pounds -- and lots of energy. One of the goals of the clinic is to use medications with few side effects, so the children can have good quality of life, Sholler said.

That benefit is much appreciated by Regan. Her son has battled cancer for nearly half his life. At 21 months, he was diagnosed with neuroblastoma, a tumor of the peripheral nervous system that typically strikes children 6 and under. The cancer went into remission six months later, but resurfaced when Ryan was 5.

At times, he was treated with high doses of chemotherapy that required three weeks in the hospital for recovery., Regan said.

"We have to drive here, but it's worth it," she said. "His quality of life is awesome."

The clinic is attracting patients from throughout the country and Canada, said Dr. James Fahner, head of pediatric oncology at the hospital. Six children have been treated so far and, eventually, Fahner expects a half-dozen children a week at the clinic.

The clinic's initial focus is on children whose disease has nor responded to therapy, whose cancer has recurred and those whose cancer is so high-risk at diagnosis that standard treatments are not likely to work.

The Haworths said in a statement they made the donation because they believe in the work of the children's cancer program.

"We want to be an encouragement to Dr. Sholler in advancing the science and we look forward to learning about the results of this new initiative," Dick Haworth said.