Giving children new hope
with new drugs

Dr. Steven D. Weitman

by Joanne Shaw

Oleander, shark cartilage, shark liver, plants from distant lands--these are just a few of the substances that have been tested as potential anti-cancer agents in the Health Science Center's search for new drugs to help patients fight the often deadly disease. That search has brought new drugs and new hope to both children and adults.

About three years ago the Institute for Drug Development (IDD), located in the Texas Research Park, began a pediatric drug development program directed by Steven D. Weitman, MD, PhD, assistant professor of pediatrics. Supported in part by the National Institutes of Health, Dr. Weitman has three different labs and tiers of research at the IDD.

The first tier involves research on new agents' interactions with tumor cells in test tubes or culture dishes. In the second tier, new agents are tested with excised tumors. In the third tier, the newly developed drugs' effects on animals with cancer are studied.

"We start at ground zero with an idea," said Dr. Weitman. "Compounds are sent to us from all over the world for our initial evaluation to look for any signs of anti-tumor activity. The last one was ‘cat's claw'--a plant--sent to us from the Chilean Andes Mountains.

"Each lab is designed to identify any activity," he said. "If there is some, the active substance is moved on to the next lab, until we get to the last stage. The last stage is giving the compound to a child or to an adult to see if everything we've learned so far is really true--if the compound has potential activity against cancers.

"The whole process takes about a year to 18 months to complete, which is much better than it used to be," Dr. Weitman added. "This is an accelerated process in which we're trying to rapidly get new agents to patients who need them."

During the program's short history, Dr. Weitman and his team have helped bring two new pediatric cancer-fighting agents into use, rebeccamycin and MGI 114. During preclinical work, Dr. Weitman discovered that rebeccamycin looked attractive because of its activity against a number of pediatric tumors. "The first patients treated with rebeccamycin were children here in San Antonio," said Dr. Weitman, listing Santa Rosa Children's Hospital and the Cancer Therapy & Research Center (CTRC) as the therapy sites. Now the drug is being tried at numerous health centers throughout the United States.

"Another agent that soon will go through trials in the United States is MGI 114," added Dr. Weitman. "We actually did some of the first laboratory work with MGI 114, and because of the activity we've seen against both adult and pediatric tumors, that agent went into clinical trials in adults and will go into clinical trials here for children."

Trained as an oncologist, pediatrician and pharmacologist, Dr. Weitman said the approach of coupling the pediatric drug development program with a strong adult program lends to its success and makes the Health Science Center's program unequaled. "Our approach is unique, and you can't find it at any other institution. I firmly believe that the only way a pediatric program can be successful in this area is if it's coupled with a very strong adult program," he said. He credits Charles A. Coltman Jr., professor of medicine and president and chief executive officer of the CTRC, and Daniel D. Von Hoff, MD, clinical professor of medicine and director of research at the CTRC, for initiating and supporting the program. The drug development work of Anne-Marie R. Langevin, MD, assistant professor of pediatrics, was also cited.

Most of Dr. Weitman's time is spent working with his research team in a laboratory, looking for new agents. The patients he often sees are those who have been termed "end stage." "You never know how well a new treatment is going to work," Dr. Weitman said. "When you're talking to families about a new therapy, the first question is, ‘How many other patients with this type of tumor have you treated with this therapy?' Many times I have to say, ‘None.'

"About 7 percent to 10 percent of patients termed terminal who go into an early clinical trial will actually have a response," added Dr. Weitman. "That's not a big number, but on the other hand, those patients otherwise would have no hope."


Currently, there are 75 open drug protocols at the Howard A. Britton, MD, Children's Cancer and Blood Disorders Center at Santa Rosa Children's Hospital, the only Minority-Based Community Clinical Oncology Program for pediatrics in the United States as designated by the National Cancer Institute. John H. Drake, RN, assistant professor of pediatrics, oversees compilation of research data for the numerous treatment plans, along with Valerie D. Sellers, RN, and Margaret C. Lewis, RN, both Health Science Center research nurses. All protocols are subject to review by the Institutional Review Boards of Santa Rosa Hospital and the Health Science Center, a process that requires approximately three months. "Because pediatric cancer is relatively rare," explained Drake, "we may have protocols open that we haven't put anybody on--when a patient does qualify for one, though, there's no waiting."

Added Sellers, "Since we're the only Phase 1 institution in San Antonio for pediatric patients, we're able to try any new, approved treatment." In Phase 1 trials new agents are given to humans (in the center's case, children) for the first time.

The nursing team collects data on patients who are being treated according to standardized protocols, in an effort to determine the best way to treat children with cancer, explained Anthony J. Infante, MD, PhD, professor and head of the hematology, oncology and immunology division of the department of pediatrics. "There just aren't enough patients with a specific type of cancer at any one location to accumulate enough data or enough statistical power to really make solid conclusions. That's why the Health Science Center participates in the Pediatric Oncology Group (POG)."

Other member institutions of POG also collect such data, and the group meets biannually to discuss optimum treatment options for various types of children's cancers.

Dr. Weitman concluded, "Hopefully, someday we won't have to do development like this and Phase 1 trials, because we'll be at the point where we're curing everyone right at the very start. When a child is first diagnosed, I want to be able to look mom in the eye and tell her we are going to be able to cure her child."

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