Cellular and humoral responses after multiple injections of unconjugated chimeric monoclonal antibody MOv18 in ovarian cancer patients: a pilot study.

PURPOSE: Chimeric antibody MOv18 (c-MOv18) mediates antibody-dependent cellular cytotoxicity (ADCC) in vitro. To study the toxicity of c-MOv18 and its immunological effects, five ovarian cancer patients received intravenous injections for 4 weeks. METHODS: ADCC activity of c-MOv18 was tested in a (51)Cr-release assay using IGROV1 and KB cells. Patients' peripheral blood mononuclear cells (PBMC) were phenotyped for CD3, CD4, CD8, and CD25 by FACS analysis and tested for T-cell proliferation in vitro in the presence of c-MOv18 with and without IL-2. RESULTS: Toxicity was mild and transient. No human anti-chimeric antibodies were found. Increased ADCC levels corresponding with a slight increase in CD4+ and CD8+ fractions were observed after the first injection, while the CD4/CD8 ratio and the levels of CD25 remained unchanged. c-MOv18 did not have a mitogenic effect on patients' PBMC and adding IL-2 did not change the degree of proliferation. In three patients stable disease was achieved for up to 4 months, 9 months and 14 months, respectively. CONCLUSION: Immunotherapy aiming at the patient's immunological capacity has minor effects in ovarian cancer patients that have been heavily pretreated with chemotherapy. Such strategies should be evaluated in patients who are more immunocompetent, i.e., before excessive chemotherapy and after achieving microscopic or small volume disease.

Clinical and technical evaluation of the ACS:OV serum assay and comparison with three other CA125-detecting assays.

BACKGROUND: In this study the clinical and technical performance of the CA125- detecting Bayer ACS:OV immunoluminometric serum assay was compared with three other well-established CA125-detecting assays. METHODS: A total of 1112 serum samples was included in this evaluation: 462 from apparently healthy women, 153 from patients with benign ovarian disease, 163 from patients with malignant ovarian disease, 10 from patients with borderline ovarian malignancies and 78 samples from 12 ovarian cancer patients during monitoring of disease. Serum samples from women with malignant endometrial (n = 68) and colon (n = 32) diseases were also included. Moreover, serum samples from women with benign uterine disease and endometriosis (n = 136) plus 10 serum samples from men (n = 7) and women (n = 3) with human anti-mouse antibodies (HAMA) after immunoscintigraphy were included. All samples were tested in duplicate with the Bayer ACS:OV, the Centocor CA125 II, the Abbott IMx CA125 and the Roche (formerly Boehringer Mannheim) Enzymun-Test CA125 II assays. RESULTS: The clinical performance of the Bayer ACS:OV assay, assessed in various patient groups, was similar to that of the two other automated assays. In serum from patients with benign diseases the highest values were found in patients with benign ovarian tumours. In the ovarian cancer patients followed during the course of disease we found similar marker patterns with all four assays. In contrast to the Roche Enzymun-CA125 II assay and to a lesser extent the Centocor CA125 II assay, the Bayer ACS:OV assay was less sensitive to interference from HAMA. CONCLUSION: The Bayer ACS:OV assay is a precise and reliable test for the quantification of CA125 in serum.

Vaginal electrical stimulation of the pelvic floor: a randomized feasibility study in urinary incontinent elderly women.

BACKGROUND: To evaluate the effectiveness of intravaginal electrical stimulation (ES) of the pelvic floor for urinary incontinence in elderly women, and to determine whether ES of the pelvic floor is a preferable treatment for urinary incontinence in elderly women. METHODS: Postmenopausal women (age 65 years or older) were enrolled in a randomized clinical trial and underwent every-other-day ES of the pelvic floor, or a daily Kegel exercise (KE) program. Objective outcome variables were: (1) Urinary leakage (during a standardized PAD test), (2) pelvic muscle strength (measured by a perineometer), and (3) detrusor instability (on ambulant urodynamic registration). Subjective outcome variables were women's subjective assessment of change in urinary symptoms based on the PRAFAB score. Twenty-four women treated with ES and 11 women treated with Kegel exercises completed the 8-week study program. The Chi-square test was used for statistical analysis. RESULTS: No significant improvement in objective outcome variables was observed in the population treated with ES compared with the population treated with KE (with 29.2% vs. 36.4% of the women showing objective improvement in measured urinary leakage). Neither was subjective improvement significant, with 29.2% vs. 27.3% of the women reporting improvement in the amount of urinary leakage. CONCLUSIONS: Although the number of enrolled women was very small this study shows that: 1. Treating elderly women with vaginal ES of the pelvic floor has a high physical and emotional cost for the individual. 2. The effectiveness of ES of the pelvic floor in urinary incontinent elderly women is low. 3. There is no great discrepancy between objective amelioration (PAD test) and subjective amelioration (PRAFAB score/quantity of urinary leakage), if the objective improvement is adequately defined. 4. It is not reasonable to advise elderly women with urinary incontinence to undertake this treatment procedure. The effectiveness of treatment does not compensate for the long-lasting and intense treatment protocol. 5. We terminated this study because of the negative outcome with ES.

The differential diagnostic potential of a panel of tumor markers (CA 125, CA 15-3, and CA 72-4 antigens) in patients with a pelvic mass.

OBJECTIVE: The purpose of this study was to assess the differential diagnostic potential of a combination of CA 125, CA 15-3, and CA 72-4 antigens in the definition of malignant disease, especially ovarian carcinoma in patients with a pelvic mass. STUDY DESIGN: A total of 412 patients were evaluated in a multicenter, retrospective study. RESULTS: Two hundred twenty-six malignant, 171 benign pelvic tumors (of which 129 were benign ovarian tumors), and 15 borderline tumors were evaluated. One hundred thirty-three patients had ovarian carcinoma. In 76 cases (55%), the International Federation of Gynecology and Obstetrics stage was III or IV. Borderline tumors (n = 15) were excluded from the statistical calculations. CA 125 antigen was the most sensitive marker for ovarian carcinoma (81%). The highest specificity and positive predictive value was obtained with CA 15-3 antigen (95% and 92%, respectively). Considering a concomitant elevation of all 3 markers as positive, a positive predictive value of 97% was found. However, only 28% of the patients in the total group and 41% of the patients with ovarian carcinoma had a concomitant elevation of all 3 markers. The combination of all 3 markers with levels below the cut-off resulted in a (false-positive) positive predictive value for malignancy between 12% and 36%. With the use of logistic regression analysis, we found a correct prediction in 73% of the cases. CA 15-3 antigen makes the most significant (P <.0001) contribution to the logistic model in the prediction of malignancy in the total group, with all pelvic masses with an odds ratio of 3.86. CONCLUSION: The combination of a simultaneous elevated level of CA 125, CA 15-3, and CA 72-4 antigens was predictive for malignant disease in almost all cases. However, such concomitant elevation was found in few of the malignant masses. Logistic regression analysis revealed that CA 15-3 antigen makes the most significant contribution to a model for the prediction of malignancy in the total group. The logistic model gave a correct prediction in 73% to 83%. The present tumor marker panel seems inferior to combinations with other test modalities, which include ultrasonography and/or physical examination and/or menopausal status or age.