Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group.

PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.

Preliminary analysis of the behavior of stage I ovarian serous tumors of low malignant potential: a Gynecologic Oncology Group study.

PURPOSE: From December 1983 through February 1992, a prospective study designed to determine the clinical course of patients with ovarian tumors of low malignant potential (LMP) was conducted by the Gynecologic Oncology Group (GOG). MATERIALS AND METHODS: This protocol was developed to evaluate the following (1) the biologic behavior of ovarian LMP tumors, (2) the effectiveness of melphalan chemotherapy in patients with clinically detectable residual disease after surgical staging and in patients whose tumors progress or recur after surgical therapy, and (3) the response rate to cisplatin in those who failed to respond to melphalan therapy. The study group consisted of 146 assessable patients with stage I serous LMP tumors. All of these women had the affected ovary (or ovaries) removed, and a complete staging operation was performed in each case. While 123 patients had a total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO), 21 retained the uterus and one normal-appearing ovary and fallopian tube. No adjuvant chemotherapy or radiation therapy was administered to any patients in the stage I study group. RESULTS: The median follow-up time was 42.4 months (range, 1.6 to 108). Thus far, no patient with a stage I ovarian serous LMP tumor has developed recurrent disease. CONCLUSION: Stage I ovarian serous LMP tumors rarely, if ever, recur. Limited resection, after meticulous surgical exploration, is adequate therapy for women of reproductive age.

The process of carcinogenesis for endometrial adenocarcinoma could be short: development of a malignancy after endometrial ablation.

Endometrial ablation has been proposed as an alternative to hysterectomy for the treatment of dysfunctional uterine bleeding. We describe what we believe to be the first reported case of an endometrial adenocarcinoma that may have developed shortly after endometrial ablation.

Long-term experience with a totally implanted catheter system in gynecologic oncologic patients.

A significant number of gynecologic oncologic patients require intravenous chemotherapy. Peripheral venous access frequently becomes difficult, necessitating reliable central venous access. This study was done to retrospectively review our experience with completely implanted venous access ports (ports). There were 100 women from 1984 to 1992 who received 115 ports. These ports remained in situ on average 350 +/- 2.3 days for a total of 110 patient years; 38 ports were in place for more than one year. An average of six courses of chemotherapy were given through each port. There was no statistically significant difference demonstrated in the complication rate secondary to site or side of placement (p = 0.5). Catheter performance in 77 percent of the patients was impeccable. We conclude that implantable ports are a safe and reliable method of chronic venous access in gynecologic oncologic patients requiring intravenous chemotherapy. Although ports reduce the number of complications and manipulations associated with percutaneous catheters, they are not devoid of problems.

Vaginal length and sexual function after colpopexy for complete uterovaginal eversion.

OBJECTIVE: Our objective was to evaluate vaginal length and sexual function after colpopexy for complete uterovaginal eversion. STUDY DESIGN: Measurements of postoperative vaginal length were performed on 59 patients having various types of repair for complete uterovaginal eversion. Sexual function was evaluated when possible. Controls were 61 normal premenopausal and postmenopausal patients both with and without a uterus. Anatomic measurements from the introitus to the middle of sacrospinous ligament and to the sacral promontory were obtained from 21 fresh autopsy specimens. RESULTS: Average vaginal length for controls was 9.2 cm in premenopausal patients with a uterus and 8.5 cm for patients without a uterus and averaged 8.5 and 8.2 cm, respectively, for postmenopausal patients with and without a uterus. Vaginal length after posterior culdeplasty was 9.2 cm, 8.2 cm after sacrospinous fixation, and 11.3 cm after sacral colpopexy. CONCLUSION: If maximum vaginal length is the objective, it is best maintained with a sacral colpopexy.

A prospective evaluation of transvaginal sonography for detection of ovarian disease.

OBJECTIVE: Despite the expanding role of transvaginal sonography in routine gynecologic examinations, as well as in screening for ovarian cancer, recent reports have noted problems when using the procedure for detecting ovarian masses and visualizing the ovaries in postmenopausal women. Our study was designed to assess prospectively the capability of transvaginal sonography in evaluating the ovary and detecting adnexal masses. SUBJECTS AND METHODS: Transvaginal sonography was used to examine 113 ovaries in 59 women within 72 hr before gynecologic surgery. Ovarian size and echo texture were assessed, and a search was made for adnexal masses. Sonograms were interpreted without knowledge of the clinical history or results of physical examination, and the sonographic findings were compared with surgical and pathologic data. RESULTS: In the 22 premenopausal patients, 16 (76%) of 21 histologically normal ovaries were identified on sonograms, but only 13 (59%) of 22 adnexal masses. Lesions as large as 177 cm3 were not detected. In the 37 postmenopausal patients, 12 (20%) of 59 normal ovaries and six (54%) of 11 adnexal masses were identified. Five malignant masses (largest, 113 cm3) were not detected. CONCLUSION: In this selected population, our ability to detect normal postmenopausal ovaries and ovarian masses was suboptimal in a number of cases. Practitioners should be aware of potential limitations in the use of this technique alone to evaluate the ovary.

Pseudomyxoma peritonei: treatment with intraperitoneal 5-fluorouracil.

Four patients with pseudomyxoma peritonei associated with mucinous tumors of the ovary were treated with cytoreductive surgery followed by intraperitoneal (IP) 5-fluorouracil (5-FU). CA-125 was elevated in three, and ca cinoembryonic antigen (CEA) in one patient; both fell to within normal levels following treatment. Two patients underwent reassessment laparotomy and one a reassessment laparoscopy with no evidence of disease following chemotherapy. The fourth patient refused surgical reassessment but remains clinically free of disease. Intraperitoneal 5-FU appears to be effective in pseudomyxoma peritonei. Précis: Four patients with pseudomyxoma peritonei associated with ovarian tumors were successfully treated with surgery and intraperitoneal 5-FU.

Teniposide (VM-26) in patients with non-squamous-cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group.

Twenty-three evaluable patients with non-squamous-cell carcinoma of the cervix were treated with teniposide 100 mg/m2 per week administered as a 30-60 min infusion. Escalations of 20 mg/m2 per week to a maximum dose of 160 mg/m2 were performed in patients without toxicity. Thirteen of the 23 patients had no prior chemotherapy. One patient had a partial response (95% confidence intervals for response less than or equal to 19%). Toxicity was minimal. Seven patients had white blood cell counts of less than 2,000/mm3 but only one had less than 1,000/mm3. No patients had platelet counts less than 50,000/mm3, and no bleeding or septic episodes were noted. Two patients had mild nausea and seven had mild nausea and vomiting. Teniposide displays no major activity in patients with non-squamous-cell cervical cancer.

A randomized comparative trial of carboplatin and iproplatin in advanced squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group study.

A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.

Intestinal variant of ovarian endodermal sinus tumor.

A case of ovarian endodermal sinus tumor (EST) with exclusive intestinal differentiation in a 28-year-old black woman is reported. The tumor cells form irregular glands with focal early Paneth cell differentiation resembling intestinal Luberkuhn's crypts. Clinical and pathological features as well as immunohistochemical findings are described.

Repair of old complete perineal lacerations.

Our subjects were 32 patients whose old complete perineal lacerations were repaired in the 10 hospitals in the South Hampton Roads Metropolitan area over a 20-year period. The layer technique of repair (26 patients) and the Warren flap procedure (6 patients) were used. Function improved in 24 of 26 patients (92%) with adequate follow-up. Function was completely restored in 22 of 26 patients (85%). The use of a careful mechanical and antimicrobial bowel prep is emphasized, as is the debatable use of the paradoxical incision (Miller).

Tumor implantation after diagnostic laparoscopic biopsy of serous ovarian tumors of low malignant potential.

Two cases of tumor implants occurring in the abdominal trocar sites after diagnostic laparoscopic biopsies of ovarian papillary serous tumors of low malignant potential are presented. To the authors' knowledge, there have been no previous reports to describe tumor implants in the abdominal trocar sites after diagnostic laparoscopic biopsies of ovarian tumors of low malignant potential.

Malignant melanoma presenting as a unilateral ovarian neoplasm.

A 45-year-old female with a unilateral ovarian melanoma without residual ovarian teratoma or clinical evidence of primary lesion is described. The clinical and pathological differential diagnosis is discussed.

"Posterior culdeplasty": revisited.

A 22-year-old retrospective review was made of 68 cases treated by the technique of posterior culdoplasty. Indications were moderate to large enterocele (40), complete procidentia (18), and complete prolapse of the vaginal vault after hysterectomy (10). Indications, techniques, and complications are presented. The wedge culdoplasty of Torpin gave good results in moderate-sized enteroceles. The "posterior culdeplasty" of McCall gave very good long-term results (2 to 22 years), especially in the group of patients (28) with complete vaginal eversion who were desirous of maintaining their sexual function.

Complications from intraperitoneal radioactive phosphorus in ovarian malignancies.

A retrospective study of the use of phosphorus-32 in the treatment of 73 cases of ovarian malignancy to evaluate the safety and morbidity is presented. The surgically confirmed major complication rate with P-32 alone was 4 of 54 cases (7.4%). The addition of external radiation raised the surgically confirmed complication rate to 4 of 19 cases (21%) and with the addition of those diagnosed and treated only medically the rate rose to 8 of 19 cases (42%). In Stage I cases, Grades 1 and 2, there was only 1 death in 26 patients (96%), whereas for Grade 3 tumors only 6 of 12 patients (50%) were living at the end of 2 years.

Emphysematous pyelonephritis in a patient with diabetes mellitus and total pelvic exenteration.

A case of emphysematous pyelonephritis in a women with diabetes mellitus who previously underwent total pelvic exenteration is presented. The emergency nature of this syndrome and its therapy are discussed.

Normal pregnancy and delivery following conservative surgery and chemotherapy for ovarian endodermal sinus tumor.

Management of younger patients with early stage ovarian endodermal sinus tumor who desire to have children can be a challenging problem. However, after an adequate and thorough staging procedure for the patient's tumor status, a Stage Iai endodermal sinus tumor may be treated with conservative surgery only, followed by chemotherapy. Successful pregnancy and delivery following unilateral adnexectomy and chemotherapy for ovarian endodermal sinus tumor have been reported only once [J. P. Forney, Obstet. Gynecol. 52, 360 (1977)]; the second reported case is presented here. It should be pointed out that strict follow-up and reliability of the patient are mandatory for such conservative therapy.

Radioactivity in blood and urine following intraperitoneal instillation of chromic phosphate in patients with and without ascites.

Systemic distribution of radioactive colloidal chromic phosphate P 32 after intraperitoneal instillation was studied in 10 patients with ovarian or endometrial malignancies. Seven patients without ascites received chromic phosphate P 32 for positive peritoneal washings, rupture of the capsule of the cyst during operation, or minimal Stage III disease. Three patients received chromic phosphate P 32 for recurrent ascites after multiple abdominal paracenteses. Blood and urine radioactivity measurements were performed at selected intervals. There was a clear statistically significant difference (p less than 0.01) between chromic phosphate P 32 activity levels in whole blood, red blood cells, and plasma in patients with and without ascites.