Early Changes in CA125 After Treatment with Pegylated Liposomal Doxorubicin or Topotecan Do Not Always Reflect Best Response in Recurrent Ovarian Cancer Patients

Abstract

Key Words. CA125 • Biomarkers • Ovarian cancer • Response to therapy • Pegylated liposomal doxorubicin Topotecan ABSTRACTPurpose. To examine early changes in CA125 relative to objective response in patients with recurrent ovarian cancer treated with pegylated liposomal doxorubicin (PLD) or topotecan and to compare the CA125 trends between the two chemotherapeutics. Patients and Methods. Patients with recurrent ovarian cancer, all of whom had measurable or evaluable disease, were randomized to receive 50 mg/m 2 PLD every 28 days (n ‫؍‬ 239) or 1.5 mg/m 2 topotecan for 5 days every 21 days (n ‫؍‬ 235) as part of a previously reported multicenter study. CA125 measurements were obtained prior to therapy and with each cycle of administration. Assessable patients underwent radiographic evaluation for response after two cycles of therapy. Objective responses were compared to trends in CA125 values at the end of cycles 1 and 2. CA125 changes were categorized as baseline (؎10%), ؎10%-25% variance, and >25% variance.Results. Among patients treated with PLD, 50% of complete responders (CR) and 41% of partial responders (PR) had increases in CA125 from baseline to cycle 1. Increases in CA125 were also seen in topotecantreated patients; however, fewer patients had increases (20% and 8%, respectively). Overall, 15% of responding patients (CR ؉ PR) receiving PLD and 6% receiving topotecan had elevated CA125 after two cycles of therapy. For those patients achieving a partial response, 19% of PLD-treated patients and 8% of topotecantreated patients had CA125 levels above baseline at cycle 2.Conclusions. Considerable intrapatient variation in CA125 values is present among responding patients. Early increases in CA125 may not predict ultimate outcome, especially in PLD-treated patients. The Oncologist

Lack of reliability of CA125 response criteria with anti‐VEGF molecularly targeted therapy

“…[5][6][7][8][9] There has been considerable interest in biologic therapeutic strategies in epithelial ovarian cancer. However, CA125 has not yet been validated as a marker of outcome in patients treated with biological therapies.…”

“…Moreover, there have also been published reports that have questioned whether CA125 overestimates responses or disease progression compared with imaging. 9,33 It is controversial whether CA125 criteria or objective imaging criteria are the more important response criteria when assessing patient disease on therapy. Our study would have a similar response rate if CA125 criteria or RECIST imaging criteria were used exclusively (53% vs 47%); the elevation in response rate to 67% (10 of 15) occurred with the use of both criteria together.…”

CA125-related Measures of Tumor Kinetics and Outcome of Patients with Recurrent Ovarian Cancer Receiving Chemotherapy: A Retrospective Evaluation

“…A more precise timing for assessing CA125-related tumor response than that of currently used GCIG criteria could allow a more simple comparison among trials. Furthermore, TR8 could allow to bypass the problem of a transitory increase of CA125 that occurs after treatment with some drugs, such as pegylated liposomal doxorubicin (PLD), and does not correlate with a radiologic progression by RECISTs or by GCIG criteria (10). A CA125 early pseudo-progression occurred in a patient of the present study after the first cycle of CT with PLD.…”

Predicting the Response of Advanced Cervical and Ovarian Tumors to Therapy

“…This considerable interpatient variation adds to the difficulty in predicting eventual outcome (95).…”