Lack of protective effect of thromboxane A2 synthetase inhibitor (CGS-13080) on radiated canine intestine

112

SOCIETY OF GYNECOLOGIC

Survival of ovarian carcinoma patients undergoing second-look laparotomy after primary surgery and adjunctive chemotherapy was evaluated by retrospective chart review. From August 1976to August 1987, 103patients with stage I-IV disease underwent reexploration. All patients were clinically free of disease. Patients with ovarian tumors of low malignant potential or other synchronous gynecologic malignancies were excluded. Forty-nine patients with a negative second-look had a 2- and S-year actuarial survival of 91 and 80%, respectively. Prognostic factors contributing to a negative second-look included early (stage I or II) disease and an optimal tumor debulking (P < 0.01). Fifteen of the 49 patients with a “negative” second-look demonstrated recurrent tumor from 12.5 to 52.5 months after reexploration. Ten of the 15 patients had recurrence documented more than 24 months after secondlook. Overall, 14of the 28 patients with stage III disease and a “negative” second-look have developed recurrence. Fifty-four patients with a positive second-look had 2- and 5-year actuarial survival of 47 and 34%, respectively. Although type of initial chemotherapy and adequacy of primary debulking surgery were not significant factors, the size of the residual tumor was correlated with survival after a positive secondlook. Patients with smaller implants had statistically longer survivals and disease-free intervals than those with large tumors (>2 cm). Fortyfour percent of 16 patients with microscopic disease have survived more than 5 years after reexploration. However, only 1 of 19 patients with bulky (>2 cm) disease could undergo a successful secondary debulking of tumor. 75. Transvaginal Sonography (TVS) as a Screening Method for Ovarian Cancer. R. V. HIGGINS, B. ENDICOTT, C. WOODS,J. R. VAN NAGELL, JR., E. S. DONALDSON, H. H. GALLION, AND E. J. PAVLIK, University

of Kentucky, Lexington, Kentucky 40536. Real-time ultrasonography, using a 5 MHz endovaginal transducer from a Phillips SDR 1550 Ultrasound Unit, was performed on 501 asymptomatic women age 40 or over. Women with a palpable pelvic mass on clinical examination, pelvic symptoms, or a history of pelvic radiation were excluded from the study. Two hundred forty-six patients (pts) were premenopausal and 255 were postmenopausal. The clinical characteristics of the pts were as follows: gravidity, 2.8 (O-IO); weight, 152 Ibs (95-318); and height, 64.5 in. (58-73). Ovarian volumes were calculated for each ovary using the prolate ellipse formula: length x width x thickness x 0.523. In addition, each ovary was examined for the presence of cystic or solid components, internal septations, or excrescences. An abnormal scan was defined by an ovarian volume 2 8 cm’ in postmenopausal women or 2 18cm3 in premenopausal women. Seven premenopausal pts (2.8%) and five postmenopausal pts (2.0%) had abnormal scans. The mean ovarian volume in premenopausal pts with abnormal scans was 40 cm’ (15-70) and 184 cm’ (13-570) in postmenopausal pts. To date, four of five postmenopausal pts with abnormal scans have undergone surgery with the following findings: ovarian adenocarcinoma, 1, and ovarian serous cystadenoma, 3. Likewise, histologic findings in five of seven premenopausal pts with abnomal scans undergoing surgery were ovarian cystic teratoma, 2, and endometrioma, 3. TVS is a painless, noninvasive method which provides accurate assessment of ovarian size and morphology. Its value as a screening method for ovarian cancer is discussed. 76. A Prospective, Randomized Trial of Topical Intet$eron-a (INF) Gels for the Treatment of Vulvar Intraepithelial Neoplasia III (VIN III). N. M. SPIRTOS, L. H. SMITH, AND N. N. H. TENG, Division

of Gynecologic Oncology, Stanford University School of Medicine, Stanford, California 94305-5317. Twenty-one patients were prospectively randomized into a blinded double-armed cross-over study comparing INF-(r (lo6 IU in a 3.5% aqueous methycellulose base) + 1% nonoxynol-9. Ten and 11 pattents

ONCOLOGISTS-ABSTRACTS were randomized to arms with and without 1% nonoxynol-9, respectively. Patients in each arm applied the gel to the affected areas q 8 hr on a daily basis and were seen biweekly. If the lesions failed to decrease in size over 8 weeks, the patient was rebiopsied and crossed over onto the other arm of the study. For the purposes of evaluation, 17 patients were treated with INF-(Y alone. Seven of 17 (41%) achieved complete responses (biopsy proven with at least I year follow-up). One additional patient achieved a partial response with at least a 50% reduction in the total surface area of all lesions present (PR). Of the 6 patients crossed-over onto this arm, only l/6 (17%) had PR. Thirteen patients were treated with INF-a plus 1% nonoxynol-9. Two of 13 (15%) had CRs and 4/13 (31%) had PRs. Two patients in this group were found to have invasive cancer on subsequent biopsy, with 1 of these succumbing to metastatic disease. Two of 3 (67%) crossed-over onto this arm also had PRs. Overall 9/21 (43%) treated had CRs and 8/21 (38%) had PRs. Thus 17/21 (41%) of patients demonstrated some response to INF-(Y applied topically. One of 21 (5%) patient complained of fever, chills, or had a significant change in her CBC or differential. These data support the conclusion that INF-c~ is an active agent in the treatment of VIN III. Further work is needed to determine if better results can be achieved by modifying either the dose or schedule of the drug. 77. Results of Radiotherapeutic Management of Primary Carcinoma of the Vagina. S. REDDY, V. S. SAXENA, S. REDDY,* M. S. LEE, E. L. YORDAN, J. E. GRAHAM, R. PHILLIPS,? AND G. D. WILBANKS,

Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois 60612; tLutheran General Hospital, Park Ridge, Illinois 60068; and *Albany Medical College, Albany, New York 12208. Forty-five previously untreated patients (pts) with primary carcinoma of the vagina were treated with curative radiotherapy from 1965through 1985. All pts were staged according to the FIG0 system. One pt was classified as stage 0, I5 as stage I, 22 as stage II, 6 as stage III, and I as stage IV. Treatment consisted of intracavitary radiation alone in stage 0 pts. Stage I pts received intracavitary/interstitial radiation alone or in combination with external pelvic radiation. All pts with higher stage disease than above received a combination of external radiation and an implant when feasible. All pts except one were followed either until death or for a minimum of 2 years. The absolute 2-year survival rates were 100% for stage 0, 87% for stage I, and 77% for stage II pts. None of the pts with stage III or IV disease survived. Of the pts who failed, all except one did so within 16 months after diagnosis. Pelvic failure as the first site of failure occurred in 86% of the pts who failed. Distant failure as a component occurred in 20% of all failures. Complications as a consequence to therapy occurred in 18% of the pts. Vaginal necrosis that healed with conservative treatment was seen in 4 pts and the other 4 pts had rectal complications. Two were of Grade I severity, 1 was of Grade II, and the other was of Grade III severity. Thus, curative radiotherapy is an effective method of treatment, with acceptable morbidity, in pts with early stage primary carcinoma of the vagina. 78. Lack of Protective Effect of Thromboxane (CGS-13080) on Radiated Canine Intestine. R. KAMATH, J. HARBERT, J. TORRISI,M. NEWSOME, AND G. DELGADO, Georgetown

A2 Synthetase Inhibitor J. BARTER, D. MARLOW, FOEGH, W. BARNES. J.

Medical Center, Wash-

ington, D.C. 20007. Thromboxane A2 is a component of the arachidonic acid cascade that causes vasospasm with platelet aggregation and, therefore, may be a likely agent in radiation-induced injury. To test this hypothesis we treated one group of five canines with a thromboxane A2 inhibitor (CGS-13080).Another group of five untreated dogs served as the control. Both sets were subjected to radiation of the ileum. Six weeks later the animals were sacrificed and specimens were obtained for blood flow

-------I SULIC

--=‘=‘---^“‘y I Y UC CI Y N CLULUUII

analysis. Blood flow was determined by using the radioactive microspheres cerium (Ce14’) and chromium (C?‘). The Cr” data show the blood flow in nonradiated bowel segments was 31.0 ml/min/lOO g, significantly greater than the 19.46 ml/min/lOO g in radiated bowel segments (P < 0.01). The blood flow in CGS-13080-treated subjects was 18.3 ml/min/lOO g in the control (no significant difference). The Ce”’ data reveal similar findings, but also indicate a washout phenomenon. Using this blood flow model in radiated canine intestine, we could show no protective effect by thromboxane A2 synthetase inhibitor (CGS-13080) in the dimunition of blood flow following radiation. 79. Plationol (P)f5FU (F) for Ovarian Epithelial Cancer (OC) Patients (pts) Failing after P-Based Combination Therapy. W. GROSH, W. ANDERSON, P. TAYLOR, R. HEIDER, AND P. UNDERWOOD, University of Virginia, Charlottesville, Virginia 22908. Twenty-four pts with OC, progressing after prior P-based combination therapy, were treated with P/F and were retrospectively reviewed to assess clinical response, toxicity, and response indicators. Twenty-two of 24 pts had initial Stage III/IV disease. Seventy-one percent had poorly or undifferentiated OC. Eleven of 24 pts received P/F as primary salvage after relapsing despite P-based treatment. Fourteen of 24 pts received P/F on relapse of other secondary salvage programs, including 7/24 pts relapsing after radiation salvage therapy. Median number of cycles of P prior to P/F was 8 (range 3-12). Twenty-three of 24 pts received at least 50 mg/M* IV of P q 4 weeks; and at least 500 mg/M’ F IV continuous 24-hr infusion x 24 hr q 4 weeks. Nine of 24 pts had unusual disease sites at the initiation of P/F (4 liver; 1 liver/spleen; 1 lungs; 1 lung/paracardium; 1 supraclavicular node; 1 skin). One of 24 pts had a CR (19+ mos) on P/F; 7/24 had a PR; 9124 had stable disease; and7124 had progressive disease. There was only l/4 pts who responded to P/F salvage when they progressed on initial treatment. The response rate after X-ray salvage was 2/7. Response to P/F was unassociated with initial stage, grade, type of prior therapy, or dose of P given with F. Responses tended to be associated with sustained initial CR, or response to initial treatment. Toxicity, none life-threatening, was severe enough to alter therapy in 14/24 pts, and consisted of neurotoxicity (9/24); hematologic (9/24); renal (2/24); GI (2/24); and fatigue (2/24); multiple toxicity was often expressed in individual pts. Toxicity was not more likely in pts with prior RT. We conclude that P/F retains respectable activity when compared to more toxic regimens among these pts with OC failing after heavy and prolonged prior treatment. 80. Eficacy of the Metastatic Survey in the Staging of Gestational Trophoblastic Disease. V. HUNTER, E. RAYMOND, C. CHRISTENSEN, G. OLT, J. SOPER, AND C. HAMMOND, Duke University Medical Center, Durham, North Carolina 27710. Between 1965 and 1987, 192 patients (pts) with normetastatic and 134pts with metastatic gestational trophoblastic disease (GTD) underwent initial metastatic survey. These pts were evaluated for characteristics which might predict the presence of “high risk” metastasis before a full radiographic survey is obtained. Minimal staging evaluation of all patients included history and examination, quantitative hCG level, chest X-ray, and evaluation for brain and liver metastasis with radioclide or CT scans. High risk metastasis was defined as metastasis outside lungs, vagina, or pelvis. Fifteen pts had high risk sites of metastasis; all of these also had metastasis in lungs or vagina. Eleven of fifteen had at least one other high risk factor and 13/15 had obvious symptoms or signs related to high risk metastasis. Based on this data we recommend that asymptomatic pts be screened at presentation for therapy of GTD with examination, hCG level, and chest X-ray. Further radiographic imaging is used only for pts with signs or symptoms, identifiable lung or pelvic metastasis, or other high risk clinical factors. Using this

ONCOLOGISTS-ABSTRACTS

113

criteria pts with high risk metastasis can be identified with sensitivity of 100% or specificity of 63%. Aproximately 60% of pts do not require further radiographic evaluation. 81. Surgical Staging in Advanced Cervical Cancer. V. HUNTER, C. CHRISTENSEN,T. BLAZCK, J. SOPER,W. CREASMAN, AND D. CLARKEPEARSON,Duke University Medical Center, Durham, North Carolina 27710. Between July 1978and December 1986,64 patients underwent staging laparotomies for assessment of retroperitoneal lymph node metastases. These patients had Stage Ic to IVa cervical cancer. Surgical approach was transperitoneal (n = 17) or retroperitoneal (n = 47). Patients with positive paraaortic nodes were subsequently treated with extended field radiation. The purpose of this review is to compare perioperative and postoperative complications of type of surgical approach and to assess long-term survival between standard and extended field treatments. No significant differences were found between type of surgical approach and operative time, estimated blood loss, hospital stay, and time to radiation treatment. In the perioperative need for blood transfusion, a significant difference was found with transperitoneal approach greater than retroperitoneal approach. No other significant differences were found between type of surgical approach and perioperative or longterm postoperative complications. Nine patients had positive paraortic nodes. Seven of nine received extended field radiation to the paraaortics. One of seven was alive at 2 years. Surgical staging in advanced cervical cancer resulted in peri- and postoperative complications similar to all exploratory laparotomies. Surgical staging delayed onset of radiation therapy by 19 days. Extended field radiation in patients with positive paraaortic nodes offered no benefit to survival. 82. Impact of CIN Diagnosis and Treatment on Self-Esteem and Body Image. T. MCDONALD, J. NEUTENS, AND L. FISCHER, University of Tennessee Medical Center at Knoxville, Knoxville, Tennessee 37920. The purpose of this investigation was to ascertain the impact of CIN (cervical intraepithelial neoplasia) on the self-concept and body image. Twenty-one subjects were recruited from a colposcopy clinic at a university medical center. They were interviewed using the adjective generation technique initially without knowledge of colposcopic results. Subsequent interviews occurred upon receiving the results, the day of surgery, and follow-up visits. Data analyses include t tests, one-way ANOVA, and correlations. Pertinent results show significant differences between how the patient sees herselfand the anxiety she is experiencing; between self-concept and femininity; between anxiety about the body and about the medical condition; between degree of femininity and body image; between how one feels about oneself and how one feels about one’s body; and between how one feels about oneself and how anxious one is about her body. Greatest concerns were for cancer, STD spread, medical procedures, sexual functioning, loss of attractiveness, reproductive functioning, and partner rejection. One hundred percent of the subjects were concerned about cancer and almost threequarters of the subjects were concerned about sexual functioning. Further, while personal anxiety was high, self-esteem was quite low. The patients did see themselves as feminine even though their body image was poor. These findings and others provide specifics to the health care professional in dealing with the psycological stresses associated with CIN. 83. Placental Site Trophoblastic Tumor (PUT): A Clinical and Therapeutic Assessment. J. LATHROP, S. LAUCHLAN, I. LATHROP, R. NAYAK, AND M. AMBLER, Women & Infants Hospital, Rhode Island Hospital and Brown University, Providence, Rhode Island 02903. PST-I’, an unusual variant of trophoblastic disease, has been recognized