Starting chemotherapy when first signs reappear not especially effective, study finds
New research finds that women with ovarian cancer relapse who start chemotherapy as soon as levels of a biomarker for the cancer rise don’t live significantly longer than women who wait until symptoms begin to reappear.
Blood levels of the marker, known as CA125, often precede the reappearance of symptoms in an ovarian cancer relapse, but there has been some debate on the usefulness of monitoring CA125 levels.
“I think the main outcome of this study is going to be to give people confidence that we’re not compromising anybody’s treatment [if we delay chemotherapy],” said Dr. Andrew Berchuck, director of the division of gynecologic oncology at Duke University Medical Center in Durham, N.C.
And the test cost is miniscule (about $50) compared to tens of thousands of dollars for many other tests, he added.
When the results of the study were first released at a large cancer gathering, The Society of Gynecologic Oncologists issued a statement saying that “although there may not presently be a major survival advantage to the use of CA125 monitoring for earlier diagnosis of recurrence, patients and their physicians should still have the opportunity to choose this approach as integral to a philosophy of active management that includes participation in trials of novel therapies. Other patients, particularly those with a less robust performance status, might be more suitable for watchful waiting with an emphasis on quality of life.”
This paper, the first randomized trial to look at the timing of chemo in women with recurring ovarian cancer, appears in the Oct. 2 issue of The Lancet, a special themed issue on cancer.
The study involved 529 women who were in remission from ovarian cancer and who were having their CA125 levels checked every three months.
Participants were randomized either to have chemotherapy early (as soon as CA125 levels doubled to twice the upper limit of normal) or later (when symptoms appeared).
Survival was about the same in both groups: 25.7 months in those who were treated early and 27.1 months in those treated later, the researchers reported.
But many of the patients in the study relapsed earlier than average, suggesting that they might have higher-risk disease, meaning one more resistant to chemotherapy, said Dr. Robert A. Burger, professor of surgical oncology and director of the Women’s Cancer Center at Fox Chase Cancer Center in Philadelphia.
“In this therapy-resistant subgroup, it may be reasonable to hold off on treatment until patients become symptomatic or to treat with a non-toxic agent, such as tamoxifen, or to enroll such patients in a clinical trial evaluating biologic therapies rather than cytotoxics,” he said. “This trial has not answered the question for patients who relapse at 12 months or later.”
Burger also pointed out there are differences in patterns of care and the availability of a wider range of drugs to treat ovarian cancer in the United States than in Europe on average. Also, treatments have improved since the study was conducted.
In the study, however, quality of life was found to be much higher among those who started chemo only after symptoms of the cancer’s recurrence, something Berchuck has seen in his own practice.
“I’ve had patients with CA125 levels going up and I know it, but I try to tell them we can’t cure cancer and there’s no evidence that treating sooner is better so they should just stay on a chemo holiday with the knowledge that they will have to go back at some point. They’ll have improved quality of life,” he explained.
Berchuck said he himself would rather know CA125 levels, even if women don’t want the results passed on, “so I know what’s going on with the disease. The key thing is not the CA125 levels, it’s what you do with the information.”
“For the first time, women can be given evidence-based advice and can make informed choices about follow-up,” the researchers wrote in the study. “The results of this trial suggest that they can opt to forgo routine CA125 monitoring if their disease is in complete remission after first-line treatment.”
Burger added, “Patients and their physicians should still have the opportunity to choose CA125 monitoring as a philosophy of active management.”
Another study in the same issue of the journal found that the chemotherapy drug cabazitaxel allowed men with metastatic prostate cancer who have not responded well to other therapies to survive a median 2.4 months longer than docetaxel.
And a third study found that adding the monoclonal antibody rituximab to chemotherapy extended the lives of patients with chronic lymphocytic leukemia.
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