Long-term survival following neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer.

The aim of this study was to analyse the long-term survival and the relationships between prognostic factors at presentation, chemoresponsiveness and disease outcome in patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery (RS). Two consecutive studies of neoadjuvant chemotherapy containing cisplatin, bleomycin plus/minus methotrexate followed by radical hysterectomy and systematic aortic and pelvic lymphadenectomy were carried out between January 1986 and September 1990 on 130 patients with > or = 4 cm stage IB2-III cervical cancer. Survival analysis was performed using the Kaplan and Meier test and Cox's multivariate regression analysis. 128 (98%) of the patients enrolled were evaluable for clinical response and survival, 83% (106) of the patients responded to chemotherapy, with a 15% complete response rate. Logistic regression analysis demonstrated that International Federation of Gynecology and Obstetrics (FIGO) stage, cervical tumour size, parametrial involvement and histotype are highly predictive of response. Responding patients underwent laparotomy, but 8% were not amenable for radical surgery. The 10-year survival estimates were 91%, 80% and 34.5% for stage IB2-IIA bulky, IIB and III, respectively (P < 0.001). After Cox's regression analysis, the parameters significantly associated with survival were the same factors predicting response to neoadjuvant chemotherapy. No stage IB2-IIA bulky patient has so far relapsed, while 12% stage IIB and 56% stage III patients recurred. The 10-year disease-free survival estimates are 91% and 44% for stage IB2-IIB and III, respectively (P < 0.001). Metastatic nodes and persistent tumour in the parametria were the only two independent factors for disease-free survival after multiple regression analysis. After a long-term follow-up (median follow-up 98 months (20-129+)), our results give new evidence of the prognostic value of response to neoadjuvant chemotherapy and of a possible therapeutic benefit of the sequential treatment adopted which, however, must be verified in a randomised setting.

Risk factors for ovarian cancer in central Italy.

OBJECTIVE: We conducted a case-control study to analyze risk factors for ovarian cancer. METHODS: Cases included 440 women (age range 13-80 years, median 54) with a histologically confirmed diagnosis of epithelial ovarian cancer who were admitted to the Gynecological Oncological Department of Gynecologic Oncology at the Catholic University Hospital in Rome, Italy. Controls were women admitted to the same hospital where cases were identified for acute nongynecological, nonhormonal, and nonneoplastic conditions. A total of 868 control women (age range 19-80 years, median 55) were interviewed. RESULTS: In comparison with ever married women, the multivariate odds ratios (OR) of ovarian cancers was 2.0 (95% confidence interval, CI 1.3-3.2) for never married women. Cases and controls were similar as regards educational status and body mass index. No clear relation emerged between ovarian cancer and age at menarche, menopausal status, and age at menopause. In comparison with nulliparae, the estimated ORs were 0.8, 0.9, and 0.7, respectively, in women reporting one, two, or three births. Women reporting two or more induced abortions were at decreased risk of ovarian cancer (OR 0.5, 95% CI 0.3-1.0). In comparison with women reporting their first birth before 20 years of age, the multivariate ORs were 1.8, 2.0, and 2.8, respectively, for women reporting their first birth at age 20-24, 25-30, and >/=31 (chi(2) trend = 10.1). Breast-feeding for more than 1 year was associated with an OR of 0.5 (95% CI, 0.4-0.8). Forty-two (9.5%) cases and 164 (18.9%) controls reported ever oral contraceptive use: in comparison with never users, the multivariate OR was 0.4 (95% CI 0.3-0.6) for ever users, and the risk decreased with duration of use. The OR for ovarian cancer was 2.9 (95% CI, 1.5-5.8) for women with a family history of the disease. CONCLUSION: This study, conducted on a relatively low-risk population, confirms the role of oral contraceptive on ovarian cancer risk and the direct association with family history of ovarian cancer. It also indicates that a later age at first birth is directly, and induced abortion and breast-feeding are inversely, related to the risk of the disease.

A combination of platinum and tamoxifen in advanced ovarian cancer failing platinum-based chemotherapy: results of a Phase II study.

The treatment of recurrent or progressive ovarian cancer has limited therapeutic potential. The clinical outcome of second-line therapy largely depends on the potential chemo-sensitivity of the tumor expressed during up-front chemotherapy, as well as on the treatment-free interval from the last course of cytotoxic therapy. However, the identification of agents such as tamoxifen (TAM) at nontoxic doses, able to act synergistically with standard chemotherapy, may be useful to overcome resistance. Fifty patients with recurrent or progressive ovarian cancer following platinum (P)-based chemotherapy (28 platinum-resistant and 22 platinum-sensitive) entered a Phase II trial to evaluate the efficacy and toxicity of P re-challenge with the addition of TAM as a chemotherapy response modulator. The choice of the P compound (100 mg/m2 cisplatin or 400 mg/m2 carboplatin, q3 weeks) was made on the basis of the prior total cisplatin dose and the presence of neurotoxicity. TAM was administered at the doses of 80 mg/day for 30 days followed by 40 mg/day for the remaining period of treatment. Toxicity consisted mainly of mild to moderate nausea and vomiting (76%), peripheral neuropathy (43%), nephrotoxicity (4%), anemia (16%), leukopenia (58%) and thrombocytopenia (16%). The overall response to the P-TAM combination was 50% (complete response 30%; partial response 20%) with a median duration of 8.5 months (3-42). Sixty-four percent of the P-sensitive and 39% of the P-resistant patients responded (59% and 33%, respectively, for those bearing measurable disease). The overall median survival was 23 (3-48) and 19 months for the patients with measurable disease (20 months for the P-resistant group). This phase II trial confirmed the activity for a re-challenge employing a P compound and TAM in clinically defined P-resistant ovarian cancer patients. The mild toxicity profile and the relatively low cost of the treatment render further investigations on the P-TAM regimen worthwhile.