Affiliations of authors: Division of Gynecologic Oncology, Oregovomab (OvaRex) Phase 3 Collaborative Trial (IMPACT II) (PTT); Division of Clinical Pathology, University of Virginia Health System, Charlottesville, VA (DMH)
Correspondence to: Peyton T. Taylor, MD, Division of Gynecologic Oncology, P. O. Box 800712, Charlottesville, VA 22908 (e-mail:ptt9y{at}virginia.edu)
Rustin et al. (1) have summarized a simplification of the guidelines for the definition of response in ovarian cancer clinical trials proposed by the Gynecologic Cancer Intergroup. The guidelines state that "Patients are not evaluable by CA125 if they have received mouse antibodies...." We believe this advisement deserves careful scrutiny and further consideration (2).
Depending on the assay, the presence of human anti-mouse antibodies (HAMA) in the serum of patients can affect the accuracy of CA125 measurements to different degrees, as determined in several pilot studies (3,4). We used samples containing varying levels of potentially interfering HAMA to assess the performance of two commonly available automated clinical CA125 assay platforms. The ImmuLite 2000 CA125 assay (Diagnostic Products, Los Angeles, CA) uses a murine anti-CA125 monoclonal antibody to capture the CA125 in the serum sample and detects bound CA125 with a polyclonal rabbit anti-CA125 antibody. The AxSym CA125 assay (Abbott Laboratories, Abbott Park, IL) uses a sheep anti-CA125 polyclonal antibody to capture CA125 in the serum and detects CA125 with a monoclonal murine anti-CA125 antibody. Both assays incorporate a wash step before quantifying CA125 in the residual sample. We posited that increasing concentrations of HAMA were more likely to influence the ImmuLite platform because of the possible binding of HAMA to the murine capture antibody.
A residual pooled serum sample from an oregovomab clinical trial (2) with a known high HAMA concentration was used to test the level of interference in both assays. This sample was serially diluted in normal human serum and enough purified CA125 (5) was added to each sample to yield a final CA125 concentration of approximately 100 U/mL. CA125 was quantified in parallel by two independent clinical pathology diagnostic laboratories. The assay results are shown in Table 1.
|
REFERENCES
1 Rustin GJ, Quinn M, Thigpen T, du Bois A, Pujade-Lauraine E, Jakobsen A, et al. Re: New guidelines to evaluate the response to treatment in solid tumors (ovarian cancer). J Nat Cancer Inst 2004;96:4878.
2 Berek JS, Taylor PT, Gordon A, Cunningham MJ, Finkler N, Orr J Jr., et al. Randomized placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. J Clin Oncol 2004;22:350716.
3 Davelaar EM, Schutter EM, von Mensdorff-Pouilly S, van Kamp GJ, Verstraeten RA, Kenemans P. Clinical and technical evaluation of the ACS:OV serum assay and comparison with three other CA125-detecting assays. Ann Clin Biochem 2003;40:66373.[CrossRef][ISI][Medline]
4 Roth HJ, Zahn I. ACS OV: an alternative to well established tests also measuring CA 125? Clin Lab 1997;43:51526.
5 Schultes BC, Baum RP, Niesen A, Noujaim AA, Madiyalakan R. Anti-Idiotype induction therapy: anti-CA125 Antibodies (Ab3) mediated tumor killing in patients treated with Ovarex mAb-B43.13 (Ab1). Cancer Immunol Immunother 1998;46:20112.[CrossRef][ISI][Medline]
Response to this Correspondence
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |