Alberto Manetta

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.

Malignant germ cell tumors of the ovary

Objective To evaluate the efficacy of adjuvant therapy for ovarian germ cell tumors. Methods We reviewed records of women who had malignant germ cell tumors of the ovary from 1977–1997. Results Seventy-two women had surgical resections of malignant ovarian germ cell tumors and most received adjuvant therapy. Fifty-six women (78%) presented with stage I disease, and 16 (22%) had more advanced disease. Tumor subtypes included dysgerminoma (n = 20), yolk sac tumor (n = 8), immature teratoma (n = 29) and mixed germ cell tumor (n = 15). Surgical management of the 56 with stage I disease consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, and extensive surgical staging in ten women, whereas a conservative surgical approach, consisting of unilateral adnexectomy with or without comprehensive surgical staging, was adopted in later years (n = 46). Fifty-six women were treated with postoperative chemotherapy, predominantly platinum-based regimens. The 5-year actuarial survival rate was 93%. None of the 36 women who presented after 1984 have died of disease. Conclusion These data confirmed that platinum-based adjuvant treatments allow most women with ovarian germ cell malignancies to have conservative surgery without compromising survival.

Comparison of adenocarcinoma and squamous cell carcinoma of the uterine cervix: A population-based epidemiologic study

OBJECTIVE Our objective was to compare epidemiologic and clinical characteristics of adenocarcinoma with those of squamous cell carcinoma of the cervix, with respect to risk by ethnic group, age at diagnosis, stage of disease at diagnosis, and survival. STUDY DESIGN All data were obtained from the Cancer Surveillance Program of Orange County, California, from 1984 through 1989. A total of 152 cases of adenocarcinoma and 457 of squamous cell carcinoma of the uterine cervix were included. RESULTS Adenocarcinoma of the cervix was diagnosed at a younger age and an earlier stage than squamous cell carcinoma. Hispanics have the highest risk for squamous cell carcinoma, whereas Asians have the highest risk for adenocarcinoma compared with whites. No differences were observed between the two histologic types in prognosis and survival. CONCLUSION Differences between the two histologic types of cervix cancer were found in the age at diagnosis, the extent of disease, and the ethnic distribution. In spite of these differences, prognosis and survival were not affected by histologic type.

Bowel obstruction in patients with ovarian carcinoma: Analysis of prognostic factors

A retrospective study was performed in which patients with both bowel obstruction and ovarian carcinoma admitted to the gynecologic oncology service at the Milton S. Hershey Medical Center between July 1, 1980, and June 30, 1987, were examined. Thirty-three patients were identified who fulfilled the inclusion criteria for bowel obstruction that did not occur in the postoperative period. Historical, physical, nutritional, and laboratory variables thought to contribute to patient survival were evaluated by a retrospective chart review. Survival time was not significantly related to presence or absence of tumor at obstruction, type of intervention whether medical or surgical, patient age, or interval from initial diagnosis of ovarian cancer to obstruction. Survival time was found to be significantly related to the prognostic index initially proposed by H. B. Krebs and D. R. Goplerud [Obstet. Gynecol. 61, 327-330 (1983)], P = 0.002. This prognostic index incorporates a multifactorial assessment of patient status including age, nutritional status, tumor spread, ascites, and prior chemotherapy and radiotherapy and can be used to evaluate patients at the time of presentation with intestinal obstruction and to help select optimal treatment for palliation.

Management of malignant, mixed mesodermal tumors of the uterus

Forty-two patients with malignant, mixed mesodermal tumors of the uterus were identified by retrospective chart review. Only 2 patients were premenopausal at the time of diagnosis. Six of the patients had previously received pelvic radiotherapy. Surgical/pathologic findings were inconsistent with clinical staging in 17 of the patients. Patients with stage I tumors were found to have extrauterine extension of tumor in 39% of the cases. Overall, 2- and 5-year actuarial survival rates were 40 and 18%, respectively. The surgical extent of disease was a major prognostic factor in patient survival (P = 0.006). Patients with tumors showing no invasion or invasion limited to the inner two-thirds of the myometrium also demonstrated a significant survival advantage as compared to those with deeper myometrial invasion (P = 0.02). However, no statistically significant relationship was demonstrated between survival and patient age, the nature of the sarcomatous element (homologous or heterologous), or the presence of cervical involvement. Patients with recurrent or persistent disease did poorly; only 4 patients have survived more than 1 year after documentation of recurrent disease. Two patients had prolonged disease stabilization with radiotherapy and cisplatin. Another patient with pulmonary metastases had a 6-month, complete response to cisplatin.

Prevention of cervical intraepithelial neoplasia and cervical cancer.

We review the current status of prevention trials in the management of cervical intraepithelial neoplasia (CIN) and cervical cancer. Two large, randomized controlled trials have shown that folic acid is inactive in reversing low to moderate grade CIN. A large randomized trial of locally applied beta-trans retinoic acid showed that the agent was effective in reversing moderate but not severe CIN. Results from a pilot trial involving 30 patients with CIN I (mild dysplasia) and CIN II (moderate dysplasia) indicate that beta-carotene can suppress CIN; a large ongoing randomized trial will answer the question more definitively.

Self-Sampling for Human Papillomavirus in a Community Setting: Feasibility in Hispanic Women

Background: The aim of the study was (a) to assess sensitivity and specificity of self-sampling in a community setting for identifying high-risk human papillomavirus (HPV) infection and abnormal Papanicolaou (Pap) smears and (b) to assess satisfaction with this collection method among Hispanic women. Methods: Lay health workers distributed self-collection kits to Hispanic women in the community. Participants collected an unsupervised vaginal sample at home or in the place and time of their preference. Results: A total of 1,213 Hispanics were included and provided a self-sample for HPV testing and were invited for a Pap smear; 662 (55%) of them had a Pap smear and the first 386 of these also had a physician-collected sample for HPV retesting. Using physician collection as the gold standard, unsupervised self-collection had a sensitivity of 90% and specificity of 88% for identifying high-risk HPV. Compared with physician sampling, self-sampling in a community setting had comparable sensitivity for identifying a low-grade lesions or greater in the Pap smear (50% versus 55%; P = 0.45) but lower specificity (94% versus 79%). Overall experience with self-sampling was reported as excellent or very good by 64% and only 2.6% reported a poor or fair experience. Conclusions: Unsupervised self-collection of vaginal samples for HPV testing in a community setting has a high sensitivity for identifying high-risk HPV and a high satisfaction among Hispanics. This approach may benefit populations with limited access to health care or with cultural barriers to cervical cancer screening. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2163–8)

Radical hysterectomy in the elderly patient : analysis of morbidity

Summary OBJECTIVE : This study compares the perioperative morbidity and mortality following radical hysterectomyof patients older than 65 years with a younger age group who underwent radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma stage IB or IIA. STUDY DESIGN : A retrospective analysis of morbidity and mortality for the first 60 postoperative dayswas conducted. The study population of 45 women >65 years of age with cervical cancer treated by radical hysterectomy was compared with a control population of 90 women RESULTS : In the elderly group, 31 of 45 and 12 of 15 were American Society of AnesthesologistsPhysical Status II and III respectively; 68/90 and 19/90 were American Society of Anesthesiologists status I and II in the younger age group ( p = 0.001). Transfusions of >2 units were required in 14% of the elderly and 35% of younger patients ( p = 0.02). No statistical differences were observed between groups for other parameters examined. CONCLUSION : Age alone should not be a contraindication for radical hysterectomy in the elderly patientwith American Society of Anesthesiologists Physical Status I to III

Pelvic exenteration: A morbidity and mortality analysis of a seven-year experience

Twenty patients have undergone pelvic exenteration at the University Hospital of the Pennsylvania State University from 1979 to 1985. The majority of operations were performed for cancers of the cervix or vagina that recurred following radiotherapy. Operative mortality was 5.0%. Of those surviving the procedure, 16 patients (84%) were rehospitalized for complications that occurred more than 30 days after exenteration. The majority of these involved the gastrointestinal or urinary tracts. Fifty-eight percent of the complications requiring surgical intervention occurred more than 1 year after surgery while 74% of the complications managed conservatively occurred within 1 year of surgery. The 2-year survival for all patients was 70%; survival decreased to 58% at 5 years. The most important risk factor for reduced survival was the extension of tumor laterally into the surgical margins.

Serum CA125 regression in epithelial ovarian cancer: Correlation with reassessment findings and survival

Findings at reassessment laparotomy and disease-free survival are reported for a group of patients with advanced-stage epithelial ovarian cancer who have had a complete clinical response to cytoreductive surgery and multiagent platinum-based chemotherapy. The predictive value of the number of chemotherapy cycles to achieve a serum CA125 of < 35 U/ml is compared to the predictive value of s, the rate of achieving a normal serum CA125. s is generated from an exponential regression model. This study suggests that s accurately predicts which patients have residual disease at reassessment laparotomy, who will be free of disease, and, of those in the latter group, who are at greatest risk to recur, as well as overall survival. If these observations are confirmed, physicians may base further therapeutic intervention on the basis of a calculated parameter following complete clinical response to first-line treatment rather than relying on findings at reassessment laparotomy.