Evaluating CA-125 Levels
CA-125 is a tumor marker often utilized for assessing disease progression or treatment response in ovarian cancer.1
CA-125 is one means of evaluation of disease progression. It should be considered along with other assessments.2
Decreases in CA-125 generally reflect a response to treatment, but are not always indicative of radiographic regression.1,3-5
- Many conditions, including endometriosis, pelvic inflammatory disease, menstruation, pregnancy, cirrhosis, and previous history of cancer, can contribute to elevated CA-125 levels1,6,7
- A single CA-125 measurement is not always definitive when predicting disease progression. Serial testing may be more reliable8
CA-125 may not always correlate with disease progression
- In a retrospective analysis of women with advanced epithelial ovarian cancer, date of progression according to clinical or radiologic criteria was compared with the date of progression according to CA-1259
- Original trial was a phase III clinical study comparing treatment with cyclophosphamide plus cisplatin versus paclitaxel plus cisplatin
- 680 patients were evaluated in this study, of whom 628 were assessable according to CA-1259

- Among patients predicted by CA-125 not to have progressed, 54% (128/239) had clinical disease progression at the last available assessment9
- One year after clinical progression was established, the false-negative rate with CA-125 was estimated (expected) to be 12.1% (1 in 8 patients)9
CA-125 changes did not always translate to response with DOXIL®
- Several studies have investigated the association of early treatment cycle CA-125 levels and response to DOXIL® for the treatment of recurrent ovarian cancer
- A retrospective analysis of one study examined changes in CA-125 relative to objective response in patients receiving DOXIL® versus topotecan; the following results were found among DOXIL®-treated patients who responded to therapy (n=40) after cycle 1:
- 50% of patients who went on to achieve a complete response (CR) (n=8) had increases in CA-125 versus baseline10
- 41% of patients who went on to achieve a partial response (PR) (n=32) had increases in CA-125 versus baseline10
- 23% of patients who went on to achieve a CR or PR had a >25% increase in CA-125 versus baseline11

- After cycle 2, 10% (4/40) of DOXIL®-treated patients who went on to achieve a CR or PR, 35% (25/71) of DOXIL®-treated patients who went on to achieve stable disease, and 55% (31/56) of DOXIL®-treated patients with progressive disease had a >25% increase in CA-125 levels versus baseline10,11
Early CA-125 elevations may not necessitate DOXIL® discontinuation
- The patient should be dosed once every 4 weeks, for as long as the patient does not progress, shows no evidence of cardiotoxicity, and continues to tolerate treatment. A minimum of 4 courses is recommended because median time to response in clinical trials was 4 months.
- In a recent retrospective study of patients with recurrent ovarian cancer, CA-125 levels were assessed at baseline and after every cycle to determine whether early changes in CA-125 were predictive of ultimate response4
- 58 were treated with DOXIL®, 99 were treated with topotecan, and 45 were treated with both agents
- Results after cycle 1 indicated that CA-125 changes were not predictive of clinical response to DOXIL®4
- Among patients who ultimately had a complete response or partial response to DOXIL® (n=17), nearly 50% actually had an increase in CA-125 after cycle 1
- After cycle 2, a decrease in CA-125 was strongly predictive of ultimate response, with 71% of DOXIL® patients showing a decrease in CA-1254
- The majority of responders to DOXIL® (10/17) had elevating CA-125 from baseline before achieving response criteria in a median 3 cycles (range, 2-6)4
- DOXIL® patients who failed to exhibit a negative drop in CA-125 levels by cycle 3 typically did not ultimately respond4
Time to CA-125 decline may vary among treatments
- In another retrospective study—a single-institution chart review—differences in CA-125 patterns with DOXIL®, topotecan, and carboplatin were assessed in populations with recurrent ovarian cancer12
- 110 patients were identified who received carboplatin (n=21) or DOXIL® and topotecan (n=89)12
- Of these, 59 DOXIL®, 60 topotecan, and 17 carboplatin patients had evaluable CA-125 levels
- Results showed that the most prominent delay in CA-125 decline was seen with DOXIL®12

- In cycle 1, CA-125 increases occurred in 69% (41/59) of DOXIL®-treated patients12
- DOXIL® patients were more likely to receive only 1 or 2 cycles of therapy than patients receiving either of the other therapies12




