'Disappointing' results may yet be reversed with longer-term study, researchers say
SATURDAY, May 30 (HealthDay News) -- The cancer drug Avastin, widely used for lung, breast and metastatic colorectal cancers, appears ineffective for patients with early stage colon cancer, a result the trial's lead author called "disappointing."
"There's no sense of building up a false sense of anticipation and drama. We failed to provide patients with a novel intervention which would increase the cure rate," said that author, Dr. Norman Wolmark, chairman of the department of human oncology at Allegheny General Hospital in Pittsburgh and chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which conducted the study.
But at a news conference, held Saturday at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Fla., Wolmark pressed the point that Avastin (bevacizumab) did bring an improvement while it was given to patients. However, this benefit vanished once patients stopped taking the drug.
"The hoped-for endpoints of the trial -- to increase the cure rate of early stage colon cancer -- were simply not met," he said. "Having said that, it is clear that there was a statistically significant transient benefit in disease-free survival during the time that [Avastin] was given, so it was effective. But, that efficacy disappeared after the year that it was given."
At one year, there was an absolute difference in disease-free survival of only 3.6 percent in favor of Avastin. And the jury may still be out on whether or not Avastin's benefits might last if patients receive it for a longer period of time. "Clearly, strong consideration should be given to clinical trials that use [Avastin] for periods of time beyond the one year that was used in this protocol," Wolmark said.
The trial, a large one involving 2,710 patients from 245 institutions, was funded by the U.S. National Cancer Institute. Drug makers Genentech and Sanofi-Aventis provided the treatment drug; Wolmark has consulted for Genentech.
Participants were randomly chosen to receive either standard chemotherapy for six months, or chemotherapy for the same period of time plus Avastin. Some patients then went on to receive six more months of Avastin.
After a follow-up of about three years, 77.4 percent of volunteers receiving Avastin were disease-free versus a very similar 75.5 percent of patients in the control group.
Other experts inserted notes of caution.
"Avastin in an adjuvant setting in this trial did not meet its endpoint which is a good surrogate endpoint for overall survival," said Dr. Vincent Chung, assistant professor of medical oncology at City of Hope Cancer Center in Duarte, Calif. "We need to tease out if any subgroups are responding better."
"With biological agents [such as Avastin], we definitely see improvements with metastatic cancer if we continue giving the drug," Chung added. "In adjuvant settings when the disease is gone, the question is how to we use biologics.''
"I would be concerned about side effects," added Dr. Otis Brawley, chief medical officer of the American Cancer Society.
Despite its vaunted status in treating a number of different tumor types, Avastin has been associated with a number of troublesome side effects, including arterial clots, heart attacks, stroke and bowel perforations.
Wolmark said his group hoped to start a trial soon looking at Avastin in the same population over two years.
A second study, also presented Saturday at ASCO, essentially discarded the notion that patients newly diagnosed with metastatic colorectal cancer should get surgery right away. Instead, the trial found that these patients can simply receive standard chemotherapy and wait until the tumor is actually causing problems -- such as a bowel perforation, intestinal blockage or bleeding -- before initiating any surgery. Early surgery is often performed in these patients to deal with complications, not to cure the disease, the researchers noted.
In the trial, "the vast majority -- 89 percent of these patients -- never developed symptoms from their colon tumor that required urgent surgical intervention," said study senior author Dr. Philip B. Paty, attending surgeon and vice chairman of clinical research at Memorial Sloan-Kettering Cancer Center in New York City. "We believe this non-surgical approach should be regarded as the standard approach for this patient population."
Other research looking at gastrointestinal cancers also turned up largely negative results.
One trial found no difference in survival for pancreatic cancer patients who received the chemotherapy regimen Gemzar (gemcitabine) or 5-FU/FA (fluorouracil/folinic acid) after surgery.
Gemzar, however, did have fewer side effects, which is "extremely important," said study lead author Dr. John Neoptolemos, head of surgery and oncology at the University of Liverpool in Great Britain. "There had been a tendency to reject 5-FU/FA and now it's very much back on stage," he said at the press conference.
And the standard of care for anal cancer -- radiation therapy plus 5-FU and mitomycin-C chemotherapy -- remains the best bet for patients with this rare malignancy. Chemotherapy with cisplatin showed no superior benefit, according to researchers at the National Cancer Research Institute in Britain. The authors also concluded that maintenance chemotherapy resulted in no added benefit. In either case, however, the prognosis was excellent, with about an 85 percent survival rate at three years.
Finally, Italian researchers from E.O. Ospedali Galleria in Genoa reported that for patients battling rectal cancer, adding another chemotherapy regimen to the standard radiation-plus-chemotherapy protocol did not shrink the tumor any further, although some initial data suggested that it may reduce the spread of the cancer.
There's more on digestive and gastrointestinal cancers at the U.S. National Cancer Institute.
SOURCES: May 30, 2009, American Society of Clinical Oncology news conference with Norman Wolmark, M.D., chairman, department of human oncology, Allegheny General Hospital, Pittsburgh; Philip B. Paty, M.D., attending surgeon and vice chairman of clinical research, Memorial Sloan-Kettering Cancer Center, New York City; John Neoptolemos, M.D., head, division of surgery and oncology, University of Liverpool, Liverpool, U.K.; study abstracts
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