Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer.

OBJECTIVE: New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis. METHODS: Asymptomatic patients with relapsed ovarian cancer who had responded to chemotherapy were enrolled and had CA125 measurements taken every 4 weeks, then more frequently when rising. Once levels reached 4 times the upper limit of normal or nadir, they started continuous tamoxifen 20 mg daily, as well as fortnightly CA125 measurements until symptomatic progression. Because of the potentially nonlinear relationship of CA125 over time, it was felt that to enable normal approximations to be utilized a natural logarithmic standard transformation [ln(CA125)] was the most suitable to improve linearity above the common logarithmic transformation to base 10. RESULTS: From 235 recruited patients, 81 started tamoxifen and had at least 4 CA125 measurements taken before and 4 CA125 measurements taken after starting tamoxifen, respectively. The mean regression slopes from using at least 4 1n(CA125) measurements immediately before and after starting tamoxifen were 0·0149 and 0·0093 [ln(CA125)/d], respectively. This difference is statistically significant, P = 0·001. Therefore, in a future trial with a novel agent, at least as effective as tamoxifen, using this effect size, the number of evaluable patients needed, at significance level of 5% and power of 80%, is 56. CONCLUSIONS: Further validation of this methodology is required, but there is potential to use comparison of mean regression slopes of ln(CA125) as an interim analysis measure of efficacy for novel cytostatic agents in relapsed ovarian cancer.

Management of asymptomatic patients on follow-up for ovarian cancer with rising CA-125 concentrations.

In most women who have been treated for ovarian cancer, serum concentrations of the tumour marker cancer antigen (CA)-125 will serially rise on average 4 months before they develop symptoms or signs of relapse. Whether or not early reintroduction of treatment produces a survival advantage is unclear. Although a high chance exists that tumour response can be achieved with chemotherapy, complete cure of these patients is rarely possible. Potential advantages of early treatment of relapse include delaying cancer-related symptoms; psychological reassurance; and, possibly, improved survival. Potential disadvantages include loss of time without treatment and the associated toxic effects. Patients should be counselled on these advantages and disadvantages before deciding whether to have their CA-125 concentrations routinely measured during follow-up. In this review, we make suggestions, on the basis of the extent and duration of response to previous treatment, as to how to manage patients once their CA-125 concentrations start rising. Our suggestions range from close observation if scans are clear to various chemotherapy regimens, hormonal treatment, and surgery. Asymptomatic patients with rising CA-125 concentrations provide an ideal group in which to test new investigational agents that might have potential as maintenance treatment.