From a cause, a cure

An allied ship carrying liquid mustard gas sank during World War II off Bari, the Italian Adriatic port. Many sailors rescued at sea later died of bone marrow failure, after they were exposed to the toxic compound that spilled into the ocean along with them.

Based on these findings, the US Defense Department sponsored reseach to determine if such chemicals could treat cancers arising in lymph nodes or blood.

The definitive experiment was first performed at Yale in the mid-1940s, on a patient with Hodgkin's disease, which regressed dramatically after treatment with nitrogen mustard, a related compound.

Welcome to chemotherapy.

Bruce Chabner, who is the clinical director of the Massachusetts General Hospital Cancer Center, tells this story to remind us that the the poisons doctors now put in our bodies to kill cancerous cells have their roots in a deadly toxin.

After the work at Yale, Chabner continues, came the experiments here in the late 1940s of Sidney Farber to repress leukemia with folic acid: ''From there emerged the whole era of looking at ways to treat cancer using drugs."

Today, chemo is part of the human condition. Most of us know someone -- a parent, a spouse, a friend, a child -- who has, or is, or will be undergoing the nightmare. Depending on the kind of cancer, some receive the poisons and leave the hospital the same day.

Others remain for 10 days or more until the drugs leave their systems. Some fare reasonably well; many others are utterly dismantled by the ordeal.

At least now, patients seem to know what they're dealing with. ''Early on, cancer medicine was a charade," says Jerome Groopman, chief of experimental medicine at the Beth Israel Deaconess Medical Center. ''Patients would be told, 'You've got a problem with your blood.' Yeah, leukemia."

Still, the question about chemo in 2006 is this: They put men on the moon, and we're still being poisoned. What gives?

It depends. ''Sometimes, not often, chemotherapy is miraculous,"says Groopman, who cites the success beginning in the '70s in the treatment of testicular cancer: ''The platinum here is Lance Armstrong."

''Ask a man in his 30s with testicular cancer if he'll put up with nausea, hair loss, risk of kidney damage, and other side effects, he'll say, 'yes,' " Groopman continues. ''Then there's the other extreme. Look at cancers like pancreatic cancer. The sound bite on a chemotherapy drug for it was 'extended life.' The fine print on the label said 'six weeks.' "

The action today is with ''targeted therapies" -- drugs that, separate from the chemo, attack cancerous cells in a variety of specific ways -- ''smart bombs versus carpet bombing," in Groopman's words.

''The whole focus now is to unravel the inner machinery of the cancer cell, to look at the distinct vulnerable pieces of that machinery," he says. ''Most of the major cancers have three or four gears that are not sequential but parallel. You throw a monkey wrench in one and the other three keep rolling."

Why not can the poisons? First, many of the targeted therapies are in early development. More important, says Chabner, ''By themselves, the targeted therapies are very weak at killing cells. Chemotherapy works better when used with these other drugs because they lower the threshold for killing these cells with chemotherapy."

So, folks, expect to be poisoned for the foreseeable future. At least the accompanying nausea has been tamed.

But with more of these targeted therapies looms the specter of cost. ''The question is, will we be able to afford the medical care involved?" asks Chabner.

Many of the new drugs are given intravenously and will be covered by most insurance plans. But they're extraordinarily expensive. Some, he says, run in the $10,000 range per monthly treatment, and can reach as high as $15,000. ''We've never really resolved the issue of controlling the cost of drugs," he adds. ''There are no price controls in the US."

One answer, he suggests, is to select more tightly those patients who can benefit most from them.

Meanwhile, Groopman notes a rise in the number of people undergoing chemo who, faced with a brutal protocol for minimal life extension of low quality, are bailing. ''There is more opportunity to make that choice because it's been aired in the culture as acceptable if not reasonable," he says. ''Also, the infrastructure exists now. There is the option of hospice care at home. This changes everything."

''People think once they've committed to chemo they have to do it," he adds. ''This is not true. I tell them this is a train they can always get off."

Such decisions raise the issue of failure for high-powered oncologists bent on success. The very definition of success, he says, has shifted from a clinical one to a spiritual one. Groopman remembers a feisty woman suffering from widespread breast cancer. ''There were no more drugs that could meaningfully help her," he recalls. ''I said, 'I have no more medicine to give you.' She said, 'No, that's wrong. You have the medicine of friendship.' "

Sam Allis's email address is: allis@globe.com