CA-125 Proves a Useful Marker to Determine Chemotherapy Response to Relapsed Ovarian Cancer
CA-125 Proves a Useful Marker to Determine Chemotherapy Response to Relapsed Ovarian Cancer
ABSTRACT & COMMENTARY
Synopsis: For relapsed ovarian cancer, investigators have used a variety of clinical measures to determine response to therapy. In this report, CA-125 levels were compared with the usual response criteria for phase II drug investigation. From 19 clinical trials including 25 different treatment groups, the CA-125 was found to correlate well with the standard criteria. Thus, this specific objective measure may be confidently used as a measure of response for treatment of relapsed ovarian cancer.
Source: Rustin GJS, et al. J Clin Oncol 2000;18:1733-1739.
Ca-125 has proven to be a useful biological marker of ovarian cancer, yet there has been some reluctance to use its measurement as a surrogate for the more comprehensive clinical analysis undertaken to determine response to chemotherapy. Thus, Rustin and colleagues at the Cancer Treatment Center and Gray Laboratory in the United Kingdom, performed an analysis on data previously reported from clinical trials of drugs in phase II for ovarian cancer. The purpose was to determine whether precise definitions of response based on serial CA-125 levels could predict the efficacy of the drugs tested.
The analysis included 14 different drugs used in 25 specific treatment groups in a total of 19 clinical trials. Response rates were estimated in 1457 assessable patients according to standard criteria (including CAT scans or ultrasonography) and in 1092 assessable patients according to CA-125. For each specific drug trial, the observed response rates were used as the input data for an evaluation of how the two criteria would perform in a hypothetical Gehan two-stage phase II trial, accepting a target drug efficacy rate of 20% and a rejection error of 5%.
A response based on CA-125 was defined as either a 50% or a 75% reduction in CA-125 levels. The 50% CA-125 response definition required four CA-125 levels, two initial elevated samples, and the sample showing a 50% decrease requiring a confirmation by a fourth sample. The 75% CA-125 response definition required only three CA-125 levels, with a serial decrease of at least 75%. In both 50% and 75% definitions, the final sample had to be at least 28 days after the previous sample.
There was concordance of the determined clinical response with the CA-125 level in 20 of 25 groups, with a less than 5% chance of rejecting the drug in nine groups and greater than 5% in 11 groups. In four groups, the drug had a less than 5% chance of being rejected by CA-125 but greater than 5% chance of being rejected by standard criteria. The difference in the classification of drugs by the standard and CA-125 response criteria was not statistically significant. Response rates using CA-125 were slightly higher than standard response rates, but only by a factor of 1.11.
Rustin et al conclude from this analysis that definitions based on a 50% or 75% decrease of CA-125 levels accurately predict which drugs in phase II trials for relapsed ovarian cancer are active and deserving of further investigation.
COMMENT BY WILLIAM b. ERSHLER, MD
Treatment of relapsed ovarian cancer, especially if the relapse occurs only after a brief cis-platinium regimen-induced remission has been discouraging, and new drugs or better combinations are clearly needed. However, a review of the phase II trial experience (such as that provided in this report) shows that the level of activity of second-line drugs used alone is marginal (from 0 to 40%, but most around 20%). In general, clinical trials in relapsed ovarian cancer are difficult because of the common inability to precisely determine tumor, even with CAT scan or ultrasound.
However, ovarian cancers do frequently express CA-125. In fact, more than 90% of women with relapsed disease will have elevated levels.1 Furthermore, decreasing levels have been shown to be associated with response to therapy,2 and have now been shown to reliably predict response to initial combination chemotherapy.3
Now, with the data presented in this study, investigators can be confident that important decisions about the drug activity in ovarian cancer can be reliably made on the basis of the serum CA-125. This could improve the accuracy of individual studies and reduce the variability observed between trials conducted at different institutions that use variable techniques for determining response. It may also reduce the cost of clinical investigation for phase II trials in relapsed ovarian cancer.
Is it sufficient to extrapolate this finding to the clinical situation in general? Probably not. Certainly a steady increase or decrease in CA-125 level is a useful marker of response; but this still must be combined with performance status, physical exam, other blood tests, and radiological procedures before decisions regarding remission, relapse, and need for additional therapy are made.
The paper set out to establish the correlation of CA-125 with the standard markers of response for this particular clinical setting (relapsed ovarian cancer). In doing so, Rustin et al are to be commended for presenting a thorough review of the published phase II experience for this condition and a very thoughtful discussion of clinical trial design. The paper is one which those learning clinical trial methodology should read.
References
1. Bast RC, et al. N Engl J Med 1983;309:883-887.
2. Tuxen MK, et al. Cancer Treat Rev 1995;21:215-245.
3. Rustin GJS, et al. J Clin Oncol 1996;14:1545-1551.
Which of the following statements about measurement of serum CA-125 in patients with relapsed ovarian cancer is true?
a. The level is elevated in 40% of patients but does not change, even in patients who respond to chemotherapy.
b. The level is elevated in 90% of patients but does not change, even in patients who respond to chemotherapy.
c. The level is elevated in 40% of patients, and a reduction by 50% following chemotherapy is likely to correlate with standard markers of clinical response, such as CT scan or ultrasound.
d. The level is elevated in 90% of patients, and a reduction by 50% following chemotherapy is likely to correlate with standard markers of clinical response, such as CT scan or ultrasound.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.