Early Chemotherapy to Prevent Ovarian Cancer Recurrence Fails to Increase Survival
Adapted from the NCI Cancer Bulletin.
A large study has found that women in remission for ovarian cancer who started chemotherapy to prevent a recurrence based on blood levels of the protein CA125 did not live longer than women who started chemotherapy only after symptoms of the disease arose.
The findings, several gynecologic cancer experts said, should influence clinical practice and make clinicians rethink how they monitor patients for recurrence and initiate additional treatments, or salvage therapies.
In an international, multicenter randomized clinical trial of more than 500 women, survival was identical between women whose treatment for recurrence was initiated based on CA125 levels and those who were treated at the onset of symptoms. CA125 can be an early indicator that their cancer has returned.
The findings of the trial were presented at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting. (The results were subsequently published October 2, 2010, in Lancet; see the journal abstract).
Most women diagnosed with advanced ovarian cancer will suffer a relapse after initial treatment, said the trial's lead investigator, Gordon Rustin, M.D., from Mount Vernon Cancer Centre in the United Kingdom. As a result, many of these women undergo regular blood tests after treatment to monitor CA125. Many women, Dr. Rustin said, become "addicted" to CA125 screening, "and it causes great anxiety."
The results of this trial, he stressed, show that "chemotherapy can be safely delayed until there are signs or symptoms of recurrence."
Women in the trial had achieved complete remission after initial treatment for advanced ovarian cancer. Half were then randomly assigned to receive treatment once their CA125 levels reached more than twice the upper limit of normal levels; the others were not informed of their CA125 levels, and treatment for recurrence was only begun when there were clinical symptoms of relapse.
Women with advanced disease tend to have multiple relapses and undergo repeated rounds of chemotherapy. In this trial, in fact, women in the CA125 arm averaged 12 more rounds of chemotherapy than those in the symptoms arm, 30 rounds versus 18. Women in the CA125 arm also began second-line chemotherapy 4.8 months earlier than those in the symptoms arm, and third-line chemotherapy 4.6 months earlier.
Because CA125 monitoring has become so ingrained in the treatment of advanced ovarian cancer, this trial "is the kind of research that's very difficult to do," said Eric Winer, M.D., chief of the Division of Women's Cancers at Dana-Farber Cancer Institute, during a press briefing. The results have the potential to improve patients' quality of life, he said.
For women in remission, a doubling of CA125 levels, even if they remain in the normal range, has been shown to herald disease relapse up to 24 months before clinical symptoms appear, said Beth Karlan, M.D., director of the Division of Gynecologic Oncology at Samuel Oschin Comprehensive Cancer Institute, following the presentation of the trial results at the meeting's plenary session.
Even so, she continued, "If early intervention with added chemotherapy does not improve overall survival and may in fact impair [patients'] quality of life, then why are we doing it?"
Because CA125 monitoring leads to more chemotherapy, Dr. Karlan noted, it may worsen cumulative toxicities, and could even impair response to future salvage treatments by hastening resistance to chemotherapy.
However, CA125 monitoring should not become obsolete, she said, noting that clinicians and patients need to be educated about the trial's results. She also recommended less frequent monitoring of CA125 in asymptomatic patients and that clinicians consider delaying palliative chemotherapy until clinical recurrence.