CA 125 Predicts Response to Chemo in Ovarian Ca

SEATTLE--In patients with advanced epithelial ovarian cancer,CA 125 concentrations after two cycles of chemotherapy are a powerfulindependent predictor of survival, a Southwest Oncology GroupStudy (SWOG) has shown.

SWOG statistician Ping-Yu Liu, PhD, and his colleagues obtainedbaseline and follow-up CA 125 levels for 101 patients enrolledin a phase III SWOG study. All patients had suboptimal stage IIIor IV ovarian cancer and were receiving chemotherapy--either cisplatin(Platinol) or carboplatin (Paraplatin) plus cyclophosphamide--every28 days for six cycles.

"We found that patients with lower CA 125 values at 8 weekshad a significantly higher chance of longer term survival,"said Dr. Liu of the SWOG Statistical Center and Fred HutchinsonCancer Research Center.

Of the 101 patients, 51 had a CA 125 level less than 35 U/mL (thecutoff for normal) 8 weeks into the study, ie, 4 weeks after thesecond course of chemotherapy. Median survival for these patientswhose CA 125 levels had normalized by 8 weeks was 26 months, comparedwith 15 months for the other 50 patients whose CA 125 values remainedabove 35 U/mL.

Similarly, for patients whose CA 125 values declined by 50% ormore from their pretreatment level, median survival was 21 monthsversus 10 months for those whose values increased or dropped byless than 50%.

"So overall, patients whose CA 125 values either normalizedor were reduced by 50% or more had an 11 month increase in theirmedian survival," Dr. Liu said.

Further analysis showed that other prognostic factors, such asage, performance status, and disease stage, could not explainthe survival difference between those patients with lower andhigher CA 125 values. "In fact, at 8 weeks, CA 125 turnedout to be the single most significant prognostic factor for survival,"he said.

"We think that an elevated CA 125 value 1 month after thesecond course of chemotherapy is an early indication of poor prognosis,"Dr. Liu said. He recommended that more research be done to evaluatealternative treatments for these patients.

At a media briefing at the American Society of Clinical Oncologymeeting in Los Angeles, where Dr. Liu presented the data, DavidAlberts, MD, deputy director, Arizona Cancer Center, Tucson, providedthe clinician's point of view.

He said that CA 125 allows the physician to make therapeutic decisionsearly on in the course of therapy, for example, to stop chemotherapyin patients who are not responding and seek alternative therapiesthat might be more effective.

"With ovarian cancer, we've had difficulty following patientsbecause the tumor is hidden," Dr. Alberts said. Pelvic examinationis "imperfect, uncomfortable, and extremely subjective,"he said, and imaging techniques such as CT scans have proved tobe "almost worthless."

CA 125, on the other hand, is a quick and inexpensive blood testthat is performed once a month. "CA 125 is probably as gooda marker for ovarian cancer as PSA is for prostate cancer, ormaybe even better, and Dr. Liu and I feel that it's time to giveCA 125 its proper place in ovarian cancer management," hesaid.

Dr. Alberts urged that all the relevant data on CA 125, includingresults of international studies, be presented to the Food andDrug Administration so that the marker can be approved for evaluatingresponse in ovarian cancer. CA 125 is currently FDA approved onlyfor monitoring ovarian cancer patients after treatment, to determinecandidates for second-look surgery, he said.