Peyton T. Taylor

Randomized, Placebo-Controlled Study of Oregovomab for Consolidation of Clinical Remission in Patients With Advanced Ovarian Cancer

PURPOSE To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study. PATIENTS AND METHODS Patients with stage III/IV ovarian cancer who had a complete clinical response to primary treatment were randomly assigned to oregovomab or placebo administered at weeks 0, 4, and 8, and every 12 weeks up to 2 years or until recurrence. The primary end-point was time to relapse (TTR). RESULTS One hundred forty-five patients were treated with oregovomab (n = 73) or placebo (n = 72). For the population overall, median TTR was not different between treatments at 13.3 months for oregovomab and 10.3 months for placebo (P =.71). Immune responses were induced in most actively treated patients. This was associated with prolonged TTR. Quality of life was not adversely impacted by treatment. Adverse events were reported with similar frequency in oregovomab and placebo groups, indicating a benign safety profile. A long-term survival follow-up is ongoing. Cox analysis of relapse data identified significant factors: performance status, CA-125 before third cycle, and baseline CA-125. Further evaluation identified a subpopulation with favorable prognostic indicators designated as the successful front-line therapy (SFLT) population. For the SFLT population, TTR was 24.0 months in the oregovomab group compared with 10.8 months for placebo (unadjusted hazard ratio of 0.543 [95% CI, 0.287 to 1.025]), a hypothesis-generating observation. CONCLUSION Consolidation therapy with oregovomab did not significantly improve TTR overall. A set of confirmatory phase III studies has been initiated to determine whether the SFLT population derives benefit from oregovomab treatment.

Oregovomab Maintenance Monoimmunotherapy Does Not Improve Outcomes in Advanced Ovarian Cancer

PURPOSE This phase III study tested the hypothesis that the CA-125-specific murine monoclonal antibody, oregovomab, administered as a monoimmunotherapy after front-line therapy in a selected ovarian cancer population would prolong time to relapse (TTR) and, ultimately, survival. PATIENTS AND METHODS Patients with stage III to IV ovarian cancer with preoperatively elevated CA-125 and objectively defined characteristics were randomly assigned 4 to 12 weeks after front-line carboplatin and paclitaxel chemotherapy to maintenance monoimmunotherapy in a fully blinded protocol. Two mg of oregovomab or placebo was infused over 20 minutes at weeks 0, 4, and 8 and then 12 weeks until recurrence or up to year 5. Patients were evaluated with serial imaging and clinical evaluation for evidence of recurrence at quarterly visits. TTR was the primary end point. RESULTS Three hundred seventy-three patients were accrued at more than 60 centers; 251 patients were assigned to oregovomab and 120 patients were assigned to placebo. The treatment arms were well balanced. There were no differences in the clinical outcomes between treatment groups. Median TTR measured from randomization after completion of chemotherapy for the integrated study was 10.3 months (95% CI, 9.7 to 13.0 months) for oregovomab and 12.9 months (95% CI, 10.1 to 17.4 months) for placebo (P = .29, log-rank test). The treatment was well tolerated. Grade 3 to 4 toxicity was reported in 24.6% of patients in the placebo group and 20.1% of patients in the oregovomab group, respectively. CONCLUSION Although oregovomab has demonstrated bioactivity, the strategy of monoimmunotherapy is not effective as maintenance therapy after front-line treatment of a favorable subset of patients with advanced ovarian cancer. Future studies of this or other tumor-antigen specific immunization strategies should seek ways to further augment induced immunity.

Gastrointestinal complications associated with pelvic exenteration

Between October, 1969, and August, 1981, 125 pelvic exenterations were performed by gynecologic oncologists at the University of Alabama in Birmingham. One hundred twenty patients underwent an exenterative procedure that required urinary diversion and a gastrointestinal anastomosis. Gastrointestinal complications accounted for 60% of all nonmalignant indications for reoperation after exenteration. The common factor in the majority of gastrointestinal complications was the presence of an anastomosis in previously irradiated small bowel. Other preoperative factors, such as significant medical disease, previous laparotomy, or malnutrition, had little apparent effect on the rate of gastrointestinal complications. Avoidance of a small bowel anastomosis by means of a colon conduit, use of an omental pedicle to bring new blood supply into the pelvis, and hyperalimentation have reduced the risk of small bowel obstruction and fistula to 2.2%, while alteration in surgical technique has decreased the rectovaginal fistula rate to 5.3%.

Paget's disease of the vulva: A report of 18 cases

Abstract Eighteen patients with Pagets disease of the vulva are reported. The frequency is approximately 19 per 1000 carcinomas of the vulva. The symptoms were present for an average of 22 mo before advice was sought, and the clinical picture was often confused with benign cutaneous lesions. This was reflected in the 20.6 mo mean delay between the first medical consultation and the definitive diagnosis and treatment. Affected margins in 9 of 15 surgical specimens indicate a more extensive spread than is usually recognized by the surgeon. The lesions often involved the labia minora, but were never limited to hairless areas. Two distinct prognostic groups were found: (1) patients with co-existing carcinoma in the vulva, and (2) patients in whom no co-existing carcinoma could be demonstrated. The Pagets cells were similar in the two groups. Five of six patients with co-existing carcinoma died of cancer 4–156 mo after the first attempt at definitive therapy. Patients without co-existing carcinoma and treated by wide surgical excision have done well. There has been no recurrence of Pagets disease in six patients in whom the margins were unaffected.

Urinary diversion in patients undergoing pelvic exenteration

Between October, 1969, and April, 1981, gynecologic oncologists at the University of Alabama Medical Center in Birmingham have performed 119 pelvic exenterations. One hundred fifteen of these patients had a concurrent supravesical urinary diversion. Fifty-six patients (48.7%) had an anterior exenteration and 59 patients (51.3%) had a total exenteration. An ileal segment was used as a conduit in 97 patients while the segment of transverse colon was used in 16 patients. Two patients had sigmoid conduits. Eighty-five patients (73.9%) had the intestinal anastomosis and conduit constructed with gastrointestinal staplers. Stapler use shortened the mean operating time for the exenterative procedure by approximately 30%. No increase in postoperative gastrointestinal complications was noted. Urinary diversion preformed as part of a pelvic exenteration has been associated with short- and long-term complications. The use of ureteral stents and the gastrointestinal staplers shortens the procedure without predisposing the patient to major urologic complications. The use of a segment of unirradiated bowel (transverse colon) in conjunction with these techniques constitutes the preferred method of supravesical urinary diversion in patients undergoing a pelvic exenteration.

Surgical staging endometrial cancer.

Nothing improves the subsequent care of a woman with endometrial cancer more than the accurate determination of the extent of her disease. A significant number of women whose malignancy is apparently confined to the uterus will have extrauterine disease after careful, complete surgical staging. The failure to detect and effectively treat unrecognized metastatic disease can have fatal consequences; the decision to prescribe potentially harmful therapy to women who do not have metastatic disease also has deleterious effects. Although the optimal surgical management of any patient must be individualized, careful and complete surgical staging at the time of hysterectomy offers the most complete data for future management.

CA125 velocity at relapse is a highly significant predictor of survival post relapse: results of a 5-year follow-up survey to a randomized placebo-controlled study of maintenance oregovomab immunotherapy in advanced ovarian cancer.

This report presents final survival survey results from a previously reported study using oregovomab immunotherapy in patients with advanced ovarian epithelial cancer. Follow-up surveys to 5 years from randomization were collected for the cohort of stage III/IV ovarian cancer patients achieving initial remission who received subsequent maintenance immunotherapy with oregovomab or placebo. The relationship of time-to-relapse, survival postrelapse, and overall survival was analyzed. One hundred forty-five patients in the intent-to-treat population and the hypothesis generating subset of 67 patients (debulked to ≤2 cm, CA125 ≤65 U/mL before cycle 3, normal CA125 and no evidence of disease postchemotherapy) previously reported were evaluated for long-term outcomes. Patterns of relapse and survival were consistent in both groups for the intent-to-treat population. Median survival time was 57.5 months for oregovomab and 48.6 months for placebo with an adjusted hazard ratio of 0.72 (95% confidence interval, 0.41-1.25). Median survival has not been reached in the hypothesis generating subset of patients receiving oregovomab. Cox multivariate regression analysis identified velocity of CA125 rise at relapse to be a highly statistically significant predictor of postrelapse outcome (P=0.006). Although time-to-relapse may be a useful surrogate of survival in ovarian cancer immunotherapy studies, 5 years of follow-up has proved insufficient to permit a definitive survival analysis and it has been extended in ongoing phase III studies of oregovomab. Velocity of CA125 rise at relapse is a highly significant predictor of survival after relapse.

Hemodynamic parameters following pelvic exenteration

Hemodynamic parameters were prospectively studied in 31 patients who underwent pelvic exenteration. With the use of a thermistor-tipped pulmonary artery catheter, hemodynamic parameters were calculated during the intraoperative and acute (less than 48 hours) postoperative interval. The mean operative time was 5.5 +/- 0.8 hours, and volume replacement (mean, 21.6 ml/kg/hr) consisted of crystalloid, colloid, and blood. Postoperative urine production (mean, 1.9 ml/kg/hr) was maintained with crystalloid (mean, 2.5 ml/kg/hr), colloid (0.2 ml/kg/hr), and blood (0.4 ml/kg/hr). Despite individual variations, the important parameters of cardiovascular function were maintained in the physiologic range. No patient developed cardiovascular or respiratory failure. We believe that the lack of perioperative morbidity and mortality was related, in substantial part, to this type of cardiovascular monitoring, which allows for the prompt diagnosis of potential problems and enables the physician to make appropriate interventions to correct these problems.

Selective arterial embolization for control of bleeding in gynecologic malignancy

Abstract Fifteen selective arterial embolizations with Gelfoam pledgets were utilized to control bleeding in 13 gynecologic oncology patients. Complications and morbidity were minimal. Embolization of neoplastic vasculature and/or major arteries supplying the pelvis controlled bleeding even when no distinct bleeding site could be determined, and proved effective in managing both acute and chronic bleeding. Methodology is outlined, and indications are discussed.

Clinical presentation of relapse in a cohort of patients (pts) with complete response to initial treatment of advanced epithelial ovarian cancer (EOC)

5048 Background: Most pts with advanced EOC experience complete response following initial surgery and platinum/taxane based chemotherapy; however, disease recurrence is common. Subsequent interventions are typically palliative. An optimal postreatment surveillance strategy to has not been established. This report evaluates the relapse patterns in a cohort of pts recently participating in a randomized phase II consolidation trial with oregovomab vs placebo [Berek JCO 22:3507]. Methods: Clinical outcomes for a cohort of 145 pts with stage III/IV EOC were assessed for the role of physical examination, CT scan and CA125 in the diagnosis of relapse. Results: 98 of 145 pts (68%) experienced clinical relapse during the observation period. Relapse was identified by physical exam in only 19% of cases (17 pelvic findings, 2 non-pelvic) and by CT in absence of physical findings in 75%. 2 pts were diagnosed on a second look laporatomy and one patient on incidental surgery. CA125, which was not used for diagnosis of ...