Pfizer Inc. and Novartis AG drugs have helped patients with the same cancer as Apple Inc.’s Steve Jobs live longer in recent studies and Stanford University, near Apple’s home base, is testing new drug combinations.
The Apple chief executive officer took a leave of absence in 2004 after saying he had a neuroendocrine tumor, a malignancy that strikes about 3,000 Americans a year. He left in 2009 for a liver transplant, sometimes done when the cancer spreads.
If Jobs’s third leave, announced to employees Jan. 17, means the malignancy is back, his treatment options now include a wave of new drugs that add months on average to survival rates, even as they carry side effects that can include fatigue, diarrhea, vomiting and low blood counts that can spur infection, doctors say. Jobs has already beaten the odds, according to a 2007 study finding that patients with the tumor die an average of three years after diagnosis.
Since then, “there have been advances that might be applicable to his case,” said John Fung, chairman of the Cleveland Clinic’s Digestive Disease Institute, in a telephone interview. “If he has a recurrence, it isn’t the end of the world.” Fung said he hasn’t been involved in Jobs’s case.
Neuroendocrine tumors create a hormone imbalance that can cause the body to improperly process calories, among other effects, according to pancreatica.org, funded by the Cancer Patients Alliance, based in Pacific Grove, California.
Trouble Gaining Weight
The Apple co-founder has had trouble maintaining weight in recent months, and immunosuppressant medications related to the transplant have made him susceptible to colds and the flu, according to a person with direct knowledge of Jobs’s health who requested anonymity because the matter is private.
Steve Dowling, an Apple spokesman, declined to comment beyond a Jan. 17 company statement that excluded details on Jobs’s health.
The leave isn’t necessarily a sign Jobs’s cancer has returned, said Abhinav Humar, clinical director of the transplantation division at the University of Pittsburgh Medical Center in Pennsylvania.
With a demanding drug regimen and scanning for infections or new tumors, “he could just need time out and recuperation,” Humar said in a telephone interview. “It could be that his medical condition isn’t severe, but the average transplant patient doesn’t have the job he does or the physical or psychological pressures he does.”
If the tumors have recurred, though, Jobs may already be on therapy that could include the cancer drug Sutent, made by New York-based Pfizer, or Afinitor, from Basel, Switzerland-based Novartis. Both have prolonged the lives of patients with advanced tumors by months in human trials.
Additionally, Stanford researchers are testing Avastin and Tarceva, medicines made by Basel-based Roche Holding AG, in combination with other drugs. All four are part of an explosion of so-called targeted therapies that attack cancer at the molecular level, holding the promise of turning intractable malignancies into chronic diseases like diabetes or HIV.
Sutent in 2006 became the first treatment simultaneously approved for two malignancies: gastrointestinal stromal tumors, or GIST, and renal cell carcinoma.
The drug works by choking off a tumor’s blood supply. In 30 percent or more of patients, it also carries side effects that can include fatigue, diarrhea, vomiting, high blood pressure and low blood counts that can lead to infection and anemia, according to Chemocare.com, a website funded by the nonprofit Scott Hamilton CARES group.
Survival Time Doubled
Sutent more than doubled the time neuroendocrine tumor patients lived without the cancer’s worsening, to 11.4 months from 5.5 months. Those figures are an average, meaning that some patients receive no benefit from the drug and die quickly, while others may gain years of added life.
The study of 171 patients, reported in a Dec. 2 Pfizer statement, led to the drug’s approval in Europe last month for use against neuroendocrine tumors.
Afinitor, which carries some of the same side effects as Sutent, works by blocking a protein called mTOR that’s needed for some cancers to grow and spread, and is used at a lower dose to prevent rejection of organ transplants.
Patients given Afinitor had no tumor growth for a median of 11 months compared with 4.6 months for those on standard supportive care, and the medicine reduced the risk of the cancer’s spreading by 65 percent, Novartis said in an Oct. 11 statement. The study was dubbed Radiant-3.
Researchers at Stanford, located near Palo Alto, California, about 20 miles north of Apple’s Cupertino offices, are testing combinations that include pertuzumab, which neutralizes the HER-2 protein that promotes tumors; Tarceva, which blocks a protein called epidermal growth factor that helps cancer cells spread; and Avastin, which hinders a protein needed by the tumor to produce new blood vessels.
Pamela Kunz, an assistant professor of oncology at Stanford, is involved in two of the studies. She said she isn’t working with Jobs and that she couldn’t answer questions about him or his case.
One trial Kunz is working on is looking at 40 patients treated with Avastin, Roche’s Xeloda and the cancer drug oxaliplatin, she said. Since the study began five years ago, 60 percent of the patients had slowed growth of their tumors and 20 percent had some tumor shrinkage.
The results were presented last year at a meeting of the American Society of Clinical Oncology, Kunz said.
A second Stanford study combines the experimental drug pertuzumab with Tarceva, Kunz said. The effects of the drug combination have been difficult to assess so far because only four patients have been treated, and some patients have suffered side effects such as severe rash and diarrhea.
Kunz said she’s still trying to determine how to follow up on the results of the three-drug study with Avastin.
“If we were going to do larger study, it would have to be involve more centers because the patient population for this disease is so small,” she said yesterday in a telephone interview. “These trials take a long time.”
James Yao, deputy chairman of gastrointestinal medical oncology at the University of Texas’s MD Anderson Cancer Center in Houston, led the 2007 study, published in the Annals of Surgical Oncology, that found a median survival of 38 months for 1,310 patients with neuroendocrine tumors. The range of the study ran from 23 months when the disease had spread to 10 years when it hadn’t.
Other researchers have also studied the success of liver transplants as a treatment for neuroendocrine tumors. In 2005, David Metz, associate chief of gastroenterology at the University of Pennsylvania in Philadelphia, published an analysis in the World Journal of Gastroenterology that suggested 60 percent or fewer of patients who underwent transplants for this purpose survive an average of 5 years.
The information, taken from individual medical centers, is of varying quality and hard to interpret, Metz said. The chance of survival may be greater today, he said.
Fourteen of 15 patients whose original tumors were removed before the transplant were still alive in 2009. Eight had lived more than three years, and four had lived five years or longer. One had lived about 15 years, she reported.
Sher is collecting data from more patients who have undergone the procedure to determine which cases are most likely to benefit, she said in a telephone interview.
Jobs’s transplant was performed by James Eason in his transplant unit at Methodist University Hospital in Memphis, Tennessee.
Eason, who declined to comment through a spokesman last week, said after the surgery in 2009 that he performs the procedure only when he is certain he can eliminate all the spreading cancer.
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