The National Cancer Institute failed to tell both government regulators and private doctors that at least four experimental drugs being given to cancer patients had potentially fatal side effects, officials of the Food and Drug Administration charged yesterday.
Dr. Michael Hensley, an FDA investigator, told a Senate hearing that cancer institute officials withheld information in their files showing that one such anticancer drug had caused severe kidney damage in animals. The drug, called MeCCNU, was given to cancer-stricken children in Boston and New York. At least 20 suffered kidney damage, some of it irreversible and fatal.
Hensley said he recommended that criminal charges be brought against some officials at both the cancer institute and the manufacturer, Bristol Laboratories, for allegedly withholding information about the drug's toxic effects. But federal investigators acknowledged that they dropped the case after interviewing only one person.
A spokeswoman for Bristol Laboratories in New York had no comment.
Cancer institute officials said they held back the evidence on kidney damage because they regarded it as preliminary.
The charges came at a hearing of the Senate Labor and Human Resources investigations subcommittee, which follows reports by The Washington Post that the cancer institute frequently has failed to adequately inform cancer patients about the dangers of experimental drugs. The chairman, Sen. Paula Hawkins (R-Fla.), criticized the institute for allowing its chemotherapy program to be eroded by what she called "the cancers of inaction, confusion, frustraton, delay and failure to communicate."
Hawkins also released an internal memorandum in which a top official of the cancer institute warned his superiors in April 1980 that the institute was failing to monitor experimental drug tests in many cases.
The FDA's investigation of the drug MeCCNU began with a letter from Paul Agostino, a retired police officer from Medford, Mass., and his wife. Agostino told the panel that in 1976, when they took their son Kevin to Children's Hospital in Boston after he developed a brain tumor, doctors there told them that MeCCNU might cause nausea and other minor side effects. But, Agostino said, they never said the drug might cause kidney damage.
"There seems to be this notion that if everyone doesn't tell you everything, you'll be better off," Agostino said. "When they tell you your son will likely die of cancer within a year, they might as well throw in the rest of the facts."
Two years later, he said, "all of a sudden, bang, someone says he's got kidney failure."
Their son, now 8, has survived the brain tumor, but both his kidneys have been seriously impaired by the drug. The Agostinos complained to FDA, thus triggering Hensley's investigation.
In early 1979, Hensley said, officials at both the cancer institute and Bristol labs told him they had no knowledge that MeCCNU caused kidney damage. It wasn't until later, he said, that "we discovered that NCI hadn't given us everything they had."
Hensley said he later learned that the cancer institute had published tests in the early 1970s showing that MeCCNU caused kidney damage in animals. Moreover, he said he learned that in May 1978 a private researcher had sent officials at the cancer institute and at Bristol similar results from his own study of the drug. That same day, Hensley said, Bristol withdrew its application with FDA to market the drug.
During the months that the institute was withholding the data, Hensley said, Kevin Agostino's doctors in Boston had no way of knowing the drug was potentially toxic, and therefore didn't monitor their young patients for kidney damage.
Hensley said he referred the case for possible prosecution to the inspector general at the Department of Health and Human Services. Linda S. Little, a special agent in that office, said she thought the allegations were important, but that because her staff was limited she interviewed only one person before the inspector general dropped the case last June.
Dr. Vincent Bono, former chief of the cancer institute's investigational drug branch, said he viewed the evidence against MeCCNU as merely "a suggestion and a hypothesis," and that he felt he had to confirm the data before notifying FDA and the doctors who were using it. NCI Director Vincent T. DeVita, however, acknowledged last week at House hearings on the subject that the institute had been "tardy" in waiting months to notify the FDA.
Bono warned his superiors in an April 1980 memo that researchers were testing such cancer drugs as Mitoxantrone without the institute's approval. "None of these studies have been sent to NCI before they were begun," he wrote. "There are many others like this."
Bono's supervisor at the time, Dr. John McDonald, said that while he didn't condone these unauthorized tests, he tried to resolve the dispute through informal discussions with the researchers because he didn't want to stifle innovation.
Other witnesses told the subcommittee in emotional tones how their families have struggled against both cancer and the drugs used to treat it. At one point, Sen. Edward M. Kennedy's voice quavered when he described his son Teddy's bout against cancer.
Donald Palmadessa, a Richfield, N.J., truck driver, said he was never warned of the dangers of MeCCNU before the drug was given to his 14-year-old son. The boy later died of kidney failure.
"We were really kept in the dark from day one," Palmadessa said. "We weren't told nothing."
"If you had the total information you have now, would you have gone ahead with the chemotherapy?" asked Kennedy, the subcommittee's ranking Democrat.
"No," Palmadessa said. "It was four years of torture."
Other witnesses criticized The Post's series as "sensational" and said it might scare dying patients away from experimental cancer drugs. One of the most optimistic witnesses was Christie Smith, 13, of Dundalk, Md., who told the panel that chemotherapy has helped her survive seven cancer operations in the last four years.
"If the doctors wanted to do anything to me, I made sure they explained exactly what would be done and if there were any side effects," she said. "I was really frightened and scared, but I knew they were doing these tests for a purpose. I didn't know if I would live or die. I just went day by day."
FDA's Hensley criticized the cancer institute for withholding information on Mitoxantrone (also known as DHAD), which he said has been implicated in at least 25 cases of congestive heart failure, including six deaths. Hensley said the institute played down evidence that the drug had killed all the dogs in two separate studies and failed to tell doctors of other studies that found the drug had damaged the hearts of rabbits, mice and rats.
Bono's successor at NCI, Dr. Daniel Hoth, said he never learned of the rabbit study because of "an internal administrative lapse," but he said there is still no conclusive evidence that the drug caused heart failure in human patients.
In a third case cited in The Post series, Dr. Robert S.K. Young, an FDA scientist, said the institute failed to tell his agency that 20 patient deaths might be related to treatment with the cancer drug Deoxycoformycin. Although FDA asked for the information in January 1980, Young said he didn't receive the cancer institute report on the drug until last week.
Another FDA official, Lee Ripper, said the cancer institute has been so lax in allowing experimental cancer drugs for dying patients that it granted several permits for an untested compound called "Jim's Juice" that an unnamed individual made in his backyard, porch and kitchen.
Dr. Rebecca Wood, an FDA chemist, said FDA management has pushed her to approve new drugs before their safety is established. "We are subjected to pressure to compromise our views and approve everything as fast as we can," she said.