Today's astonishing disease-fighting drugs and therapies are giving hope—and the possibility of a long, healthy life—to thousands of patients. Go behind the scenes with oncologists, drug companies, and the science of optimism.
Carol Turtur, 55, would rather be skiing. Or better yet, heading down the Danube by boat. But this January morning in 2006, all vacation plans are on hold. The former flight attendant is reporting to the University of Texas M.D. Anderson Cancer Center in Houston to test an experimental cancer treatment. As one of the patients in a preliminary trial, she will be helping doctors and a drug company determine whether human milk fat globule-1 antibody is safe and, if so, at what dose. She is also hoping for a miracle. For the past ten and a half years, Turtur has been battling breast cancer. “You keep waiting for the one treatment that is going to work. You want to be the one,” she says, caught up in the enthusiasm of science's new high-tech push to find a cure.
A look at Turtur's treatment itinerary shows she has tried mightily to be that pioneer. In 1995 she underwent a double mastectomy and six months of chemotherapy. But just shy of the five-year mark, a routine chest X-ray revealed inoperable breast cancer that had spread to her lungs. She refused more chemotherapy, so Francisco Esteva, MD, PhD, her physician at M.D. Anderson, treated her first with tamoxifen, the warhorse drug that inhibits estrogen's ability to promote breast cancer cell growth, and when that didn't work, with two aromatase inhibitors to lower estrogen levels. After a few months on each, with little progress against the disease, Esteva put her on a new medication called Herceptin.
Herceptin, introduced in 1998, was a revolution in the treatment of cancer—arguably the first “targeted” drug on the market. While radiation and chemotherapy indiscriminately destroy cancerous and healthy cells alike in a scorched earth policy against disease—often leaving the patient miserable and struggling into remission if she is lucky enough to live—targeted drugs elegantly block specific pathways involved in cancer cell growth. Herceptin, for example, binds to HER-2, a protein that, when present in excessive quantities on the surface of certain cells, causes a particularly virulent form of breast cancer. The drug works by attaching to those cells and halting their growth while, theoretically, healthy cells remain intact. For Turtur it had an immediate effect, reducing her cancer by half in only two months.
About six months passed before the cancer began progressing again, but this time so slowly, she didn't feel the symptoms for almost five years. In July 2005, with more than one-third of her lungs affected, she started getting winded climbing stairs. Luckily, a therapy that slows the growth of tumors by targeting their blood supply had been approved just a year earlier for colorectal cancer. At Esteva's suggestion, Turtur began taking the drug, Avastin, with Herceptin to see if it might hobble her cancer as well. This time, too, the results were astounding. By November 2005, her tumors had noticeably diminished.
Last year, when the cancer started advancing again, she hoped for the same results with human milk fat globule-1 antibody (designed to get the immune system to start attacking breast cancer cells). Unfortunately, that didn't work; nor did a second experimental targeted drug called RAD001. So last fall, Turtur started back on chemo (with Herceptin), but in a new formulation that uses nanoparticles and “is a little more targeted, if you will,” says Esteva. Amazingly, her tumors have shrunk again, her symptoms vanished.
Learning from Results
For a metastatic breast cancer patient, whose median survival rate is two to three years, she's not kidding when she says, “I feel like I've been very successful in this little war.”
Unbelievable as Carol Turtur's story is, she's not alone. While advances in oncology today can seem like a lot of little skirmishes, a new revolution in smart therapies is turning what was once a death sentence into a manageable disease.
The greatest triumph has been with chronic myelogenous (or myeloid) leukemia (CML). That story started one spring day in Oregon, the same year Herceptin arrived on the market, as Brian Druker, MD, lingered by the hospital bed of Robert “Bud” Romine, who was rapidly dying of CML. Romine, a 68-year-old former conductor on the Southern Pacific railway, had volunteered to be the “first guinea pig” two years earlier and had no further treatment options available. Neither fact, however, calmed Druker's nerves as he administered the experimental drug, Gleevec, designed to target a specific protein in leukemia cells.
Druker spent most of that day by Romine's bedside, watching his patient's every reaction. Romine's blustery humor stood him in good stead. He had already outlived his original prognosis by a year, holding on so he could try the new “miracle.” When Druker tested his vitals every few hours, Romine would assure him, “Don't worry. I'm still here.”
Romine didn't explode or expire on the spot, but the drug also didn't decrease his abnormally high white blood cell count, a telltale sign of CML. Druker couldn't believe he had let down this man who'd had so much faith in him, but was forced, according to the study's protocol, to move on to the next patient and to give a higher dose. Twelve subjects along, white blood cell counts began dropping to healthy levels and staying there. “By February or March, my patients were sharing stories of hope being restored,” Druker says. “They were planning for the future again. There were tears, including my own.”
Because of the startlingly positive success, Druker was able to convince Novartis, the makers of Gleevec, to let Romine back on the drug. Three weeks after the first treatment at the new dosage, Druker couldn't sit still while he waited for the results, pacing around, leaning against the wall. Finally, he left the room and came in again grinning ear to ear. He handed the blood count printout to Romine's wife, Yvonne. She couldn't make sense of the numbers. “What?” she asked.
“He's in the normal range,” Druker told them.
Studies would soon show that Gleevec keeps a whopping 83 percent of patients in full remission at five years—and it helped Romine for even longer. “Hell's bells,” he said when asked about Druker. “He brought me back to life.” When Romine died last May, it was from heart disease.
To date, at least 14 targeted therapies have been approved, and dozens more are in the pipeline. Challenges remain. Given that the oldest of these drugs is only nine years old, doctors still don't fully understand the long-term effects. Thanks to recent research, we now know that heart failure can be a complication in about 2 to 4 percent of subjects taking Herceptin, and a reduction in heart function in 10 percent. Heart trouble might also be a rare side effect of Gleevec, according to new research, although Druker hasn't observed it in any of his patients. (“We think Bud had early heart failure before he started the Gleevec,” he says.) And for a very few, Avastin and chemo (now approved for lung cancer) can cause fatal bleeding in the lungs.
Resistance is also a problem: Similar to the AIDS virus, cancer cells often mutate to outsmart the new drugs. Pharmaceutical companies are already working to stay one step ahead by developing an arsenal of treatments that might be given as cancer cocktails. For example, with CML, two new targeted therapies are available now to treat patients who relapse on Gleevec; several others are in development.
A cure for cancer will probably elude scientists until they better understand what causes the disease. But a new test—the MammaPrint, which predicts how likely breast cancer will reoccur—although still crude, heralds the day we've all been waiting for: when the doctor can say, “This cancer will never kill you” versus “That tumor is aggressive.”
Until then, considering the frenzy of research, cancer patients might ask their doctors if it's appropriate to join a clinical trial (listed at www.cancer.gov ). You could just be on the receiving end of a miracle.
Elizabeth Mitchell is the author of Three Strides Before the Wire: The Dark and Beautiful World of Horse Racing (Hyperion).
Printed from Oprah.com on Tuesday, March 11, 2014
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