Age contrasts in clinical characteristics and pattern of care in patients with epithelial ovarian cancer

OBJECTIVE: The objective of this study was to document and highlight aspects of ovarian cancer treatment that pertain, especially, to elderly women. METHODS: Data were collected retrospectively from all epithelial ovarian cancer patients who were diagnosed in the Gynecologic Oncology Unit at Meir Hospital, Kfar-Saba, Israel, from January 1994 to December 1998. RESULTS: The study group comprised 143 patients (<70 years n = 97, > or =70 years n = 46). Both groups presented with the same distribution of stages. The elderly group had fewer primary debulking surgical interventions (54.3%) than the younger group (84.5%) (P = 0.001)). Age was not a limiting factor in achieving optimal debulking in those patients who did undergo surgery (older 53%, younger 54%). Almost 92% of the younger patients entered a first-line chemotherapy regimen compared to 65.2% of the older patients (P = 0.001). The elderly patients were more likely to receive neoadjuvant chemotherapy (43.3.3% vs 13.4%, P < 0.01) and hematological toxicity was significantly more common (75% vs 36.3%; P = 0.001), although no significant difference was noted between the groups in Grade 3-4 patients (> or =70 years, 62.5% vs <70 years, 45.5%; P = 0.2). The elderly patients were more likely to have dose reductions and treatment delays compared to the younger patients (60% vs 22.4%; P < 0.001, and 46.6% vs 19.1%; P = 0.004, respectively) and they had similar overall response rates (RR) and complete response (80% vs 87.6% and 60% vs 71.9%, respectively). CONCLUSIONS: Older women who present with the same distribution of stages as their younger counterparts are likely to be treated more conservatively than younger ovarian cancer patients. In this study, however, when surgery was performed, the optimal tumor debulking rates were similar in each group. Although high morbidity, most often hematological toxicity, occurs in elderly patients following chemotherapy, the overall RR compared favorably with that of younger patients.     

口服耐受对实验性卵巢早衰抗透明带抗体的抑制作用研究

目的:探讨应用口服耐受的方法抑制抗透明带抗体的产生,为卵巢早衰的治疗提供一种新途径。方法:将100只小鼠随机分为对照组、模型组、小剂量治疗组、中剂量治疗组和大剂量治疗组。各治疗组小鼠给予透明带多肽灌胃,剂量分别为每次1μg、10μg和100μg,共7次。灌胃4次后,经皮下注射免疫原建立小鼠自身免疫性卵巢早衰模型。免疫荧光法检测小鼠外周血和卵巢中抗透明带抗体的表达。结果:中剂量和大剂量治疗组小鼠外周血中抗透明带抗体的阳性率分别为15%和45%,明显低于模型组的80%,具有统计学意义(P<0.01)。中剂量治疗组小鼠卵巢中抗透明带抗体的阳性率为20%,明显低于模型组的70%,具有统计学意义(P<0.01)。结论:适当剂量的透明带多肽能够很好地诱导口服耐受、抑制机体抗透明带抗体的产生。     

Clinical features and outcomes of uterine and ovarian carcinosarcoma

BACKGROUND: The objective of this study was to compare the clinical presentation and outcomes of women with ovarian and uterine carcinosarcoma (CS). METHODS: We performed a retrospective review of patients treated for uterine or ovarian CS from 1952 to 2003. Fisher's Exact Test was used to compare patient characteristics. Survival curves were estimated using the Kaplan-Meier method and compared using the log rank test. RESULTS: We identified 87 patients with uterine CS and 18 with ovarian CS. There was no difference in age, body mass index, parity, menopausal status, family history of cancer, history of pelvic radiation, diabetes or hypertension between the two groups. 43% of women with uterine CS presented at stage I/II, compared to 28% of women with ovarian tumors (P = 0.0003). 82% of patients with ovarian tumors received adjuvant chemotherapy with or without radiation; 51% of the patients in the uterine CS group received adjuvant radiation therapy. The median length of follow-up was 13 months. There was no difference in the Kaplan-Meier estimates of overall survival between the two disease sites. The median survival for uterine CS patients was 16 months, compared to 11 months in the ovarian CS group; HR = 0.991 (95% CI = 0.534, 1.839). CONCLUSIONS: We found no differences in patient demographics between the two groups. Despite differences in stage and initial treatment, there was no difference in survival between women with uterine and ovarian CS.     

Screening for insulin resistance in women with polycystic ovarian syndrome.

INTRODUCTION: Insulin resistance is implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). Insulin-sensitizing agents are increasingly used in the treatment of infertility and hirsutism in PCOS. However, not all women with PCOS are insulin-resistant. OBJECTIVE: To assess the degree of insulin resistance within a clinic population of women referred for treatment of oligomenorrhoea or infertility. DESIGN: We evaluated 25 consecutive PCOS outpatients referred for treatment of menstrual dysfunction/infertility and a matched control group. All underwent a standard oral glucose tolerance test (OGTT) with serial insulin measurements. Insulin sensitivity was calculated using homeostasis model assessment (HOMA). RESULTS: Five of the 25 clinic patients had abnormal glucose handling (two had previously unknown type 2 diabetes and three had impaired glucose tolerance). Fasting and 2-h insulin levels were significantly higher in the PCOS women. Mean HOMA-S (insulin sensitivity) was even lower for PCOS women with normal GTT status (mean (95% confidence interval): 0.53 (0.34-0.72)) than for controls (0.94 (0.84-1.04)) (F = 4.2, p < 0.001). HOMA-B (pancreatic beta-cell function) was nearly tripled for normal GTT status PCOS women at 273 (205-342) versus 105 (70-139) for controls (F = 6.8, p < 0.001). CONCLUSIONS: The results suggest a role for routine measurement of HOMA-S in identifying women with PCOS with insulin resistance with a view to targeting them with insulin-sensitizing agents.     

Meta-analysis of surgery in advanced ovarian carcinoma: is maximum cytoreductive surgery an independent determinant of prognosis?

OBJECTIVE: If maximum cytoreductive surgery benefits the survival of women with advanced ovarian cancer, the median survival time of groups of such women will improve as the proportion of women undergoing maximum cytoreductive surgery is increased. STUDY DESIGN: Fifty-eight suitable studies that encompass 6962 patients with advanced ovarian cancer were identified. Multiple linear regression was used to analyze the effects on median survival time of the following variables: the proportion of each cohort undergoing maximum cytoreductive surgery, the use of platinum-containing chemotherapy, the dose intensity of chemotherapy, the proportion of each cohort with stage IV disease, and the year of publication of the study. RESULTS: Maximum cytoreductive surgery was associated with only a small improvement in median survival time, but platinum-containing chemotherapy improved median survival time substantially. Increased dose intensity also conferred a useful survival benefit. CONCLUSION: Cytoreductive surgery probably has only a small effect on the survival of women with advanced ovarian cancer. The type of chemotherapy used is more important.     

Is age a barrier to the aggressive treatment of ovarian cancer with paclitaxel and carboplatin?

OBJECTIVE: The objective of this study was to determine whether the toxicities associated with chemotherapy are age related in women treated for ovarian cancer. METHODS: Patients with stage II-IV epithelial ovarian cancer underwent cytoreductive surgery. Adjunctive therapy was given to each patient consisting of intravenous (IV) paclitaxel 175 mg/m(2) over 3 h with a subsequent 30-min IV infusion of carboplatin. Carboplatin dose was calculated to achieve a targeted area under the curve (AUC) of 5.0-7.5. Treatment was repeated at 21- to 28-day intervals for six cycles. Toxicities were graded after each dose of chemotherapy. Results were analyzed using the Wilcoxon rank sum test and log likelihood ratio to compare toxicities in women age <60 years old to women >/=60 years old. RESULTS: Fifty-three women, 22 of whom were >/=60 years old, were treated with 309 cycles of chemotherapy. Forty-eight patients (92%) completed all six cycles. AUC dosing of carboplatin was equivalent for both groups. Carboplatin dose reduction occurred in 75% of patients for grade 4 neutropenia or thrombocytopenia. No patient required a reduction in the paclitaxel dose. Neutropenia was less frequent in women >/=60 years old than in women <60 years old (P = 0.02). There was no difference between women <60 years old and women >/=60 years old in the incidence of anemia, thrombocytopenia, or the use of growth factors. A 68% complete clinical response rate was observed in women >/=60 years old compared to a 74% complete response rate for women under age 60 (P = 0.22). CONCLUSION: Age is not a barrier to the aggressive treatment of ovarian cancer with this regimen of paclitaxel and carboplatin.     

Age-specific differences in treatment and survival of ovarian cancer patients in the province of Limburg, the Netherlands, 1986–92

de Rijke JM, Schouten LJ, Volovics A, van der Putten HWHM. Age-specific differences in treatment and survival of ovarian cancer patients in the province of Limburg, the Netherlands, 1986–92. Int J Gynecol Cancer 1998; 8 : 150–157.
The objective of this study was to investigate age-specific differences in treatment and survival of patients with epithelial ovarian cancer diagnosed in the period 1986–92 in Middle and Southern Limburg, the Netherlands.
Data about the treatment of epithelial ovarian cancer patients were derived from the population-based Maastricht Cancer Registry and retrospectively evaluated. Observed and relative survival rates were calculated according to age, stage, period of incidence and histology. Differences in survival between three age groups were explored with univariate and multivariate analyses. The patients were followed until January 1, 1994.
The total study group comprised 367 epithelial ovarian cancer patients; 86 were younger than 55 years at diagnosis, 152 were 55–69 years and 129 were aged 70 years or older. Stage III (FIGO) was the most common stage at diagnosis in the three age groups. Older women (70 +) were more likely to have received no treatment or only one treatment modality than were younger women ( P < 0.001). Five-year relative survival decreased with age: 54%, 34% and 17% in the three age groups 0–54, 55–69 and 70 + years, respectively ( P = 0.000). Multivariate regression analysis revealed that age at diagnosis was an independent significant prognostic factor.
Several exposure factors in elderly women may explain the differences in treatment and survival, such as additional comorbid conditions, more aggressive tumor growth, physicians' reluctance to treat elderly patients and less favorable social conditions.     

Long-term survival in advanced ovarian carcinoma following cytoreductive surgery with standard peritonectomy procedures

The impact of cytoreductive surgery with standard peritonectomy procedures has not been extensively assessed in the treatment of advanced ovarian cancer. The aims of the study are to report the long-term results of patients with advanced ovarian cancer undergoing cytoreductive surgery with standard peritonectomy procedures and to identify the prognostic indicators that may affect outcome. The records of 74 women with advanced ovarian cancer were retrospectively reviewed. Clinical indicators were correlated to survival. The hospital mortality and morbidity rates were 13.5% and 28.4%, respectively. Complete or near-complete cytoreduction was possible in 78.4% of the patients. Overall 10-year survival rate was 52.5%. Complete cytoreductive surgery, small-volume tumor, low-grade tumor, the absence of distant metastases, the use of systemic adjuvant chemotherapy, performance status >70%, and limited extent of peritoneal carcinomatosis were favorable indicators of survival. Complete cytoreduction (P= 0.000) and treatment with systemic chemotherapy (P= 0.001) independently influenced survival. Recurrence was recorded in 37.8% of the patients and was independently influenced by the tumor grade (P= 0.037). Cytoreductive surgery with standard peritonectomy procedures followed by adjuvant chemotherapy offers long-term survival in women with advanced ovarian cancer who have limited peritoneal carcinomatosis and no distant and irresectable metastases.     

The influence of age and co-morbidity on treatment and prognosis of ovarian cancer: a population-based study

OBJECTIVES: With the rising mean age, more patients will have one or more other serious diseases at the time of diagnosis of ovarian cancer (co-morbidity). In this study, the independent effects of age and co-morbidity on the application of treatment guidelines and prognosis were evaluated. METHODS: All patients with epithelial ovarian cancer diagnosed between 1995 and 2001 in the southern part of The Netherlands (N = 1116) were included. RESULTS: The prevalence of co-morbidity increased from 34% of the age group <70 to 63% of the older age group. Eighty-three percent of the patients with FIGO stage II or stage III younger than 70 years underwent the advised treatment (combination of surgery and chemotherapy) compared to only 45% of the patients aged 70 or older. In a multivariable analysis age, FIGO stage, presence of co-morbidity, and year of diagnosis seemed to be independent predictors of receiving the advised treatment. In multivariable analyses age 70 + (HR = 1.3, 95% CI = 1.03-1.7) and the use of both surgery and chemotherapy (HR = 0.4, 95% CI = 0.3-0.6, reference is only surgery) were independent prognostic factors for overall survival. CONCLUSIONS: Even in the absence of co-morbidity, standard combination therapy was prescribed significantly less often for elderly patients with FIGO II or III ovarian cancer. Age and combined treatment of surgery and platinum-based chemotherapy were independent prognostic factors. Co-morbidity did not seem to have a prognostic effect.     

Clinical outcomes of pregnancy with one elevated glucose tolerance test value.

OBJECTIVE: To evaluate clinical outcomes of pregnancies with one elevated glucose tolerance test. METHODS: We performed a 50 g glucose challenge test (GCT) in 5,019 pregnant women at 24-28 weeks of gestation. In 1,170 women with plasma glucose levels over 130 mg/dl, a 100 g oral glucose tolerance test (OGTT) was performed at 28-32 weeks of gestation. During follow-up, 282 patients were lost and in the 888 cases that were followed-up, 189 were excluded because of GDM. Therefore 699 study patients were divided into four groups: No Elevated group (NE, N = 577) with all four normal 100 g OGTT values, and Groups 1 (N = 16), 2 (N = 35), and 3 (N = 71) with one elevated 100 g OGTT value after 1, 2 and 3 h, respectively. RESULTS: Poor maternal outcomes (NE group, Group 1, Group 2, Group 3: 17.5%, 37.6%, 22.9%, 25.3%) with pre-eclampsia, cesarean delivery for cephalopelvic disproportion, failure to progress, or fetal distress, was highest in Group 1 (odds ratio 2.94; 95% confidence interval 1.02-8.42). Poor perinatal outcomes (15.8%, 43.1%, 14.3%, 21.1%) with any one of the following; fetal distress, Apgar score of < 7 at 5 min, hypoglycemia, respiratory distress syndrome, small for gestational age and perinatal death, was also highest in Group 1 (odds ratio 4.24; 95% confidence interval 1.02-17.52). CONCLUSION: Pregnancies with one elevated glucose tolerance test value after 1 h exhibited increased adverse maternal and perinatal outcomes compared with the group with all normal OGTT values or the groups with an elevated glucose tolerance test value after 2 or 3 h.     

A phase II double-blind randomized study of the simultaneous administration of recombinant human interleukin-6 and recombinant human granulocyte colony-stimulating factor following paclitaxel and carboplatin chemotherapy in patients with advanced epithelial ovarian cancer

PURPOSE: Recombinant human interleukin-6 (rhuIL-6) is a glycosylated cytokine with hematopoietic stimulatory effects. In particular, preclinical studies suggest the agent can stimulate thrombopoiesis, even in conjunction with chemotherapy. We attempted to determine whether higher dose chemotherapy for ovarian cancer was possible given the pharmacologic use of this important growth factor. METHODS: We conducted a randomized, double-blind phase II study of IL-6 plus granulocyte colony-stimulating factor (G-CSF) versus placebo plus G-CSF in combination with a standard chemotherapy regimen. Patients with epithelial ovarian cancer, stages Ic to IV, were eligible. All patients were previously untreated with chemotherapy and had Karnofsky performance status >/=60. rhuIL-6 (Escherichia coli, SDZ ILS 969) 1.0 micrograms/kg or placebo was given subcutaneously on days 2-8 every cycle together with G-CSF 5.0 micrograms/kg subcutaneously days 2-15, following administration of paclitaxel 175 mg/m2 as a 3-h infusion and carboplatin given to a desired AUC of 7.5 on day 1 every 21 days. RESULTS: Fifty patients were entered in this study, although the study was temporarily suspended by the FDA in midstudy over manufacturing concerns. Therefore, 37 patients were evaluable for efficacy of growth factor; 19 patients received placebo plus G-CSF and 18 rhIL-6 plus G-CSF. There was no difference in prognostic variables between these two groups. Platelet nadirs were lower in the first cycle for the placebo group (P = 0.004, Wilcoxon sum-rank test) but not in other cycles. There was no statistically significant difference in cycle treatment delays, carboplatin dose delivered, number of patients with grade 4 thrombocytopenia, or platelet transfusion. Nonetheless, the trend of the data favored IL-6 in all cases. CONCLUSIONS: This study demonstrated a minimal effect (statistically significant in the first cycle only) on thrombopoiesis in women undergoing paclitaxel and carboplatin therapy of ovarian cancer. No clinically significant effect on actual chemotherapy delivery was demonstrated, however. Future studies, if warranted, to ameliorate thrombocytopenia should be carried out with regimens producing even greater thrombocytopenia than the current regimen in the control arm.     

Premature ovarian failure in patients affected by oncohematological disease

AIM: Premature ovarian failure (POF) can be considered a consequence of chemotherapy performed in patients affected by oncohematological disease. The aim of this study was to evaluate the administration of GnRh analogs (aGnRh) to prevent gonadal toxicity associated with cancer treatment. METHODS: From April 1996 to May 2002 a total of 49 fertile women affected by oncohematological diseases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute leukemia) and treated with chemotherapy were evaluated. Ovarian function was studied through a 40.7 month observation period, after chemotherapy, in 3 different groups: women treated with aGnRh, oral contraceptives treatment and no preventive-treatment. The differences in these groups as to menstrual cycle, blood ovarian hormones, age at diagnosis, type and dosage of chemotherapy administered were evaluated. Statistical analysis was performed by chi2 test with Yates correction and Fisher test. RESULTS: All patients treated with aGnRh and chemotherapy achieved a good ovarian function. A normal ovarian function was also obtained in 75% of patients treated with oral contraceptives and only in 59.3% of women with no preventive treatment. Significant difference was found comparing aGnRh group with no preventive-treatment group (P<0.05). No significant differences were found between other groups. CONCLUSIONS: Use of GnRh analogs administered before beginning chemotherapy prevents from gonadal damage in all cases observed. Higher chemotherapy toxicity and older age at diagnosis time decrease ovarian function.     

"Dose dense" chemotherapy in ovarian cancer

Abstract.   Vasey PA. "Dose dense" chemotherapy in ovarian cancer. Int J Gynecol Cancer 2005; 15(Suppl. 3): 226–232.
In essence, dose densification is "accelerated therapy" (a commonly used phrase in radiotherapeutics) and is a form of dose intensification because the amount of drug per unit time (dose intensity = mg/m²/week) is increased. There is general consensus that increasing platinum dose intensity in ovarian carcinoma has not been proven despite a dozen or more randomized trials evaluating up to twofold increases in dose intensity. Few randomized trials in ovarian carcinoma have compared weekly "dose dense" chemotherapy with more conventional dosing schedules although there are plenty of phase II studies. In these, dose densification of single agent therapy, for some drugs at least, appears to be relatively well tolerated, with encouraging levels of activity in patients purportedly refractory to the same agents when scheduled in the standard way. However, many studies ostensibly evaluating "dose density" do not actually evaluate this entity, but actually split the standard 3-weekly dose into weekly fragments thus maintaining the same dose intensity. Furthermore, as the aim of treatment in recurrent ovarian cancer is palliation, weekly treatments are less convenient, are probably less cost effective, and have different dose-limiting toxicities. This article will review the clinical data supporting dose density as a therapeutic maneuver in ovarian cancer.     

Predictive power of clomiphene citrate challenge test for failure of in vitro fertilization treatment

BACKGROUND: To evaluate the impact of ovarian reserve on the outcome of in vitro fertilization (IVF) treatment in 140 women, in a total of 279 treatment cycles. METHODS: All women underwent a clomiphene citrate (CC) challenge test to assess their ovarian reserve before IVF treatment. One hundred and eighteen women (84%) had normal basal follicle stimulating hormone (FSH) levels (3.1-10.0 IU/l) and 22 women (16%) had elevated FSH levels (> 10.0-24.0 IU/l). The FSH levels measured on cycle day 10 showed that 106 (76%) of the women could be regarded as having a normal ovarian reserve and 34 (24%) a diminished ovarian reserve. RESULTS: In the group with diminished ovarian reserve, pregnancies and live births were dramatically lower than in the group with normal ovarian reserve. Counting only the first cycle (n = 140), the number of ongoing pregnancies and live birth rate were highly different between the two groups: 3% vs. 36% (1/33 vs. 28/78). Counting all treatment cycles (n = 210 + 69) the clinical pregnancy rate in the diminished ovarian reserve group was 6%-31% compared with the normal woman (4/69 compared 65/210). The number of started treatment cycles per woman were similar in the two groups. The length of the ovarian stimulations were slightly longer in the group with elevated FSH compared with the group with normal FSH levels. The number of cancellations resulting from insufficient ovarian response was significantly higher in the group with diminished ovarian reserve (n = 38, 55%) compared with the normal women (n = 32, 15%) (p < 0.0001). In addition, the average E2 levels before oocyte pick up were significantly lower in the group of women with diminished ovarian reserve compared with normal women (p < 0.0001). Calculation of the sensitivity and specificity of the CC test showed that an abnormal test has a high probability for a negative treatment outcome. The number of retrieved, fertilized oocytes, the number of divided oocytes, and the number of embryo transfers in the first as well as in all cycles differed significantly between the two of groups women (p < 0.001-0.009). CONCLUSIONS: We found that the CC challenge test is a useful tool in assessing a woman's ovarian capacity before infertility treatment. The predictive value of the test for a negative outcome of IVF treatment was strong. We recommend performing the test before infertility treatment. This may prevent unnecessary treatment trials and unrealistic expectations from both patients and doctors.     

Meta-analysis of cisplatin, doxorubicin, and cyclophosphamide versus cisplatin and cyclophosphamide chemotherapy of ovarian carcinoma.

OBJECTIVE: To compare the survival with cisplatin, doxorubicin (Adriamycin), and cyclophosphamide versus that of cisplatin and cyclophosphamide in women with advanced epithelial ovarian cancer, to evaluate the effect of dose intensity, and to evaluate meta-analysis methodology. METHODS: Meta-analysis was done on 30 studies of 2060 women with stages III and IV epithelial ovarian cancer. All had 3-year survival data, adequate follow-up, no other chemotherapy, no radiation therapy, and had information for various prognostic variables (age, stage, grade, and residual disease). We used four different methods of meta-analysis: pooled published data and modified effect-size analyses of the entire group (30 studies), and pooled published data and effect-size analyses of the subset of five prospective randomized studies. RESULTS: Three-year survival for the entire group was 43% for cisplatin, doxorubicin, and cyclophosphamide versus 36% for cisplatin and cyclophosphamide; for the five prospective randomized studies, the rates were 46 and 35%, respectively. The survival advantage of cisplatin, doxorubicin, and cyclophosphamide was statistically significant when analyzed by the pooled published data and modified effect-size meta-analysis of the entire group and the pooled published data meta-analysis of the five prospective randomized studies. The effect-size meta-analysis of the five prospective studies did not reach statistical significance. Total dose intensity and doxorubicin dose intensity were not significantly associated with survival advantage in cisplatin, doxorubicin, and cyclophosphamide use. CONCLUSIONS: There seems to be a survival advantage to treatment with cisplatin, doxorubicin, and cyclophosphamide versus treatment with cisplatin and cyclophosphamide. We believe this to be due to the properties of multiagent chemotherapy (the addition of doxorubicin) rather than to increased dose intensity. In addition, we believe that physicians need to familiarize themselves with meta-analysis methodology.     

Neoadjuvant chemotherapy in advanced ovarian cancer: a case-control study

The aim of this study was to compare the outcome of patients with advanced ovarian carcinoma treated with neoadjuvant chemotherapy (NACT) with those treated conventionally with primary debulking surgery. From 1994 to 2003, all consecutive cases of advanced-stage epithelial ovarian carcinoma treated with NACT at the University of Bari were identified. A well-balanced group of women who underwent primary debulking surgery followed by platinum-based chemotherapy was selected as controls. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Thirty women with advanced-stage epithelial ovarian carcinoma were treated with NACT and compared to 30 patients who underwent primary debulking surgery. Patients in the NACT were significantly older and had a poorer performance status compared to the controls. However, no statistical difference was observed in overall disease-specific survival (P= 0.66) and disease-free survival (P= 0.25) between the two groups. Although patients in the NACT group are significantly older and have a poorer performance status, this treatment modality does not compromise survival. Prospective randomized trials comparing NACT to conventional treatment to determine the quality of life and cost/benefit outcomes are now appropriate for women presenting advanced epithelial ovarian cancer.     

An immunoscintigraphic evaluation of the engineered human monoclonal antibody (hCTMO1) for use in the treatment of ovarian carcinoma.

OBJECTIVE: To assess the safety and targeting ability of the engineered human antibody (hCTMO1) in women with ovarian carcinoma. DESIGN: The monoclonal antibody labelled with Indium-111 was administered to women with suspected primary or recurrent ovarian carcinoma six days pre-operatively. The first group of women was given a dose of 0.1 mg per kg body weight of radiolabelled antibody. A second group of women received 1 mg per kg body weight and finally a third group was given 1 mg per kg body weight of unlabelled antibody followed one hour later by 0.1 mg per kg body weight of radiolabelled antibody. All the women were then imaged using a gamma camera one hour and up to 96 hours after injection. PARTICIPANTS: Fourty-four women in whom there was a high suspicion of primary ovarian carcinoma on the basis of ultrasound or CT imaging and serum CA125 and those in whom there was a suspicion of recurrent ovarian carcinoma after being treated for histologically confirmed carcinoma. SETTING: The Queen's Medical Centre, Nottingham and University Hospital Vrije Universiteit, Amsterdam, The Netherlands. RESULTS: At the low dose of antibody the sensitivity for detection of ovarian carcinoma was 70%. After increasing the dose of antibody and also after pre-dosing with unlabelled antibody the sensitivity increased to 100%, but there was a large number of false positive results at the higher dose, and therefore the specificity was low. The liver and bone marrow were the organs with the highest activities. CONCLUSION: The genetically engineered antibody hCTMO1 is safe for use in women. This antibody effectively targets ovarian carcinoma and has greater potential as a vector for therapeutic use than as a diagnostic agent.     

The Evidence for Increasing Cytotoxic Dose Intensity in the Treatment of Advanced Ovarian Cancer

Summary: There is a body of conflicting evidence regarding the place of dose intense chemotherapy for advanced ovarian cancer. It remains unproven whether dose intensity is more important than total dose delivered, and measures of drug delivery to the tumour itself are absent or crude. There are various methods under evaluation for reducing the toxicity of chemotherapeutic drugs, thus enabling larger doses to be given. However, we must not lose sight of the fact that current treatment is palliative for the majority of women, making the quality of life an important issue. The place of dose intense cytotoxic chemotherapy, for the treatment of advanced ovarian cancer, must be evaluated in large, carefully designed, prospective trials which, if possible, should include a quality of life assessment.     

Treatment patterns by decade of life in elderly women (> or =70 years of age) with ovarian cancer

OBJECTIVE: Elderly patients are less likely to receive surgery and platinum-based combination chemotherapy than younger patients. We evaluated multi-institutional management of ovarian cancer in the elderly. METHODS: Charts of women with ovarian, primary peritoneal or fallopian tube cancer from 1/1996-6/2004, age > or =70 years were reviewed. Age, stage, medical co-morbidities, surgery, chemotherapy, treatment modification, toxicity and survival were analyzed. Chi-square, logistic regression and survival analysis were used. RESULTS: Of 131 patients, 90 were ages 70-79 (group 1 = G1) and 41 were >80 years of age (group 2 = G2). Surgery was performed in 80 patients in G1; 25 patients in G2 (P = 0.001). Among patients who underwent surgery, optimal debulking and post-operative complications did not differ between groups. Ninety-five percent of patients received platinum-based therapy and 83% received combination platinum/paclitaxel in G1, compared to 90% and 41%, respectively, in G2 (P < 0.001). Of those receiving platinum therapy, 36% in G1 and 41% in G2 required dose reductions or termination of therapy. Forty percent of G1 and 50% of G2 required a delay of therapy; the majority occurring in patients receiving combination therapy. Hematological toxicity increased with use of combination therapy, but not with advancing age or Charlson score. Successful debulking surgery significantly impacted survival, and when controlling for this factor, age was not a significant variable. CONCLUSION: The extreme elderly had a decreased likelihood of receiving surgery and combination chemotherapy despite equivalent co-morbidities. In this analysis, optimal surgical cytoreduction had the greatest impact on survival.     

The usefulness of ovarian volume, antral follicle count and age as predictors of menopausal status.

OBJECTIVE: To compare the accuracy of ovarian volume, antral follicle count and age in predicting menopausal status in healthy women. METHODS: The cross-sectional study was set in the Gynecology Division at the Leonor Mendes de Barros Maternity Hospital, S?o Paulo, Brazil. The subjects of this study were premenopausal (n = 121) and postmenopausal (n = 71) healthy women aged between 40 and 55 years. They were submitted to a medical interview and transvaginal ultrasound examination. The ovarian volume (cm3), antral follicle count and chronological age were recorded in both groups and the accuracies of these parameters in predicting menopausal status were compared. RESULTS: Premenopausal women presented larger ovaries than postmenopausal women (p < 0.01). Premenopausal women had a higher number of antral follicles than postmenopausal women (p < 0.01). The receiver operating characteristic curves showed that ovarian volume, age and antral follicle count had similar sensitivities and specificities in predicting menopausal status. The best cut-off points were observed when ovarian volume was <4 cm3, age was > or =48 years and antral follicle count was < or = two follicles. CONCLUSIONS: Ovarian volume, antral follicle count and chronological age are all individually predictive of menopausal status, with similar accuracies.