Paolo Guarnerio

Reproductive factors and risk of uterine fibroids

We analyzed the relation between reproductive history and risk of uterine fibroids using data from a case-control study. Cases were 621 women with histologically confirmed diagnosis of uterine fibroids. Controls were 1,051 non-hysterectomized patients. Compared with nulliparae, parous women had a relative risk (RR) of fibroids of 0.5 [95% confidence interval (CI) = 0.4-0.6], and the risk declined with number of births. The risk of fibroids also decreased with number of induced abortions (RR = 0.8 and 0.6 for women reporting one or two or more abortions, respectively). A total of 24 cases (3.9%) and 19 controls (1.8%) reported a history of infertility (RR = 2.0; 95% CI = 1.1-3.7).

Paclitaxel 175 or 225 mg per Meters Squared With Carboplatin in Advanced Ovarian Cancer: A Randomized Trial

PURPOSE To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer. PATIENTS AND METHODS Patients with histologically confirmed epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized, multicenter study. Women were randomly assigned to treatment with (1) carboplatin at the dose (in milligrams) corresponding to the following formula: target area under the free carboplatin plasma concentration versus time curve (AUC) = 6 x (glomerular filtration rate + 25) mg/m(2) (AUC6) plus paclitaxel 175 mg/m(2) for six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m(2) for six cycles every 21 days. A total of 502 women entered the study. RESULTS Pathologic complete response was documented in 132 patients (63.8%) in the 175 mg/m(2) group and in 127 cases (55.7%) in the 225 mg/m(2) group (chi(2) P =.090). The 4-year progression-free survival rate was 41.5% (SE = 3.5) in the 175-mg group and 39.2% (SE = 3.5) in the 225-mg group. The corresponding 4-year survival rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths), respectively. CONCLUSION This randomized trial suggests that paclitaxel 175 mg/m(2) plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m(2) plus carboplatin AUC6.

Survival and prognostic factors of early ovarian cancer

Survival and prognostic factors were analysed in 150 patients with histologically confirmed epithelial ovarian cancer stage IA-IIA. The relapse-free and overall survival rates were, respectively, 81% and 88% after 3 and 74% and 84% after 5 years. The analysis of various prognostic factors indicates as the main factor the grade differentiation of the tumour.

A phase I–II trial of fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer

We conducted a phase I-II study with escalating paclitaxel doses plus carboplatin at a fixed dose for previously untreated patients with advanced ovarian cancer in order to define the maximum tolerated dose. Eligible for the study were women with a histologically confirmed diagnosis of ovarian cancer stage III-IV according to the FIGO classification. In the first phase of the study, 6 patients were allocated escalating paclitaxel doses with fixed-dose carboplatin in order to establish the maximum tolerated dose. The starting dose of paclitaxel was 150 mg/m2 given after carboplatin (300 mg/m2) every 4 weeks for a total of six courses. The paclitaxel dose step was 25 mg/m2 up to 250 mg/m2. The study then progressed to a phase II trial using the maximum tolerated paclitaxel dosage reached during the escalating dose phase. A total of 27 patients entered phase I and 23 phase II. Neurotoxicity was observed in 47 patients (94%; 29 grade 1, 17 grade 2, 1 grade 3, according to the WHO classification). The intensity of neurotoxicity tended to be dose related: out of the 15 patients who received < or = 200 mg paclitaxel, a total of 14 grade 1, but no grade 2 or 3 neurotoxicities, were observed. The frequency of grade 1, 2 and 3 neurotoxicity was 15, 17 and 1, respectively, in the 35 women who received > or = 225 paclitaxel +300 mg carboplatin. There was no clear relationship between median WBC and platelet nadir and dose level. Among other toxicities, alopecia was observed in all 50 cases, hypersensitivity in two (4%) and myalgia in 41 (82%; 34 grade 1 and 7 grade 2). These frequencies tended to increase with the dose, but the relationship was not statistically significant. The overall response rate was 78% (39/50) with a complete response rate of 62% (31/50). In conclusion, this study suggests that carboplatin and paclitaxel can be administered safely to patients with advanced ovarian carcinoma. The maximum dose reached was 250 mg/m2 paclitaxel and 300 mg/m2 for carboplatin, but from a clinical point of view the maximum paclitaxel dose we would consider safe is 225 mg/m2.

Oral contraceptives and risk of gestational trophoblastic disease.

Clinical reports suggested that the use of oral contraceptives (OC) after a molar pregnancy may increase the risk of persistent throphoblastic disease. However, few epidemiologic studies have analyzed the effect of OC use on the risk of developing gestational trophoblastic disease (GTD). To give further information, we have analyzed data from a case-control study on risk factors for GTD. Cases were 268 women with a histologically confirmed diagnosis of complete or partial mole referred to the participating Trophoblastic Disease Centers. A total of 268 subjects were interviewed; 79 cases were classified as partial and 159 as complete mole. Controls were randomly selected women who gave birth to healthy infants at term on randomly selected days in the same network of hospitals in which cases had been identified. A total of 104 cases and 130 controls reported ever OC use, and the corresponding odds ratio (OR) was 1.5 (95% CI, 1.1-2.1). The risk of GTD increases with duration of OC use: the OR was 1.7 (95% CI 1.2-2.6) for ever-users reporting >or=12 months of use. No consistent pattern of risk was observed with time since last OC use. We have analyzed separately the association between OC use and risk of complete and partial moles: no statistically significant difference emerged, but the OR for partial moles was higher (OR 3.0, 95% CI 1.6-8.4) than for complete mole (OR 1.0, 95% CI 1.8). In conclusion, we observed a weak association between OC use and GTD; such a weak association could be explained by factors other than causality.

Role of secondary surgery in relapsed ovarian cancer

In recurrent ovarian cancer secondary surgery may be an important opportunity to improve survival and quality of life. In order to give a general overview of the available evidence, we discuss published data on the role of secondary surgery in relapsing ovarian cancer. The median survival after secondary surgery has been reported ranging from 16 to 29 months, and seems to be longer in subjects with optimal debulked disease. However, as with front-line debulking, it is difficult to establish whether the secondary debulking itself has a therapeutic, or even a lasting palliative effect, or whether the patients in whom the procedure is successful are those who have more indolent disease. Any benefit of treatment must be compared with potential morbidity. Post-operative complications are reported in about 25--30% of cases, with a potential impact on hospital stay. During the natural course of the disease, most patients with ovarian cancer develop intestinal obstruction, without impairment of other vital organs or pain. Reported series have suggested that palliative surgery for bowel obstruction is generally feasible in most patients. Some prognostic factors have been suggested to identify patients likely to benefit most from palliative surgery: young age seemed to be associated with longer survival after successful surgery for bowel obstruction, though this finding was not statistically significant. The site of obstruction does not seem to be related to survival after surgery.