Mature results of a randomized trial of two doses of cisplatin for the treatment of ovarian cancer. Scottish Gynecology Cancer Trials Group.

PURPOSE: In 1992, we reported the first results of a randomized study in ovarian cancer, comprising two doses of cisplatin and indicated a significant difference (P = .0008) in median survival. Four years later, we now describe the results of this trial. PATIENTS AND METHODS: After a median follow-up of 4 years and 9 months, 115 of 159 cases of advanced ovarian cancer, originally randomized to receive six cycles of cyclophosphamide 750 mg/m2 and either a high dose (HD) of 100 mg/m2 cisplatin or a low dose (LD) of 50 mg/m2 (LD) cisplatin, have now died. RESULTS: The overall survival for HD and LD patients is 32.4% and 26.6%, respectively, and the overall relative death rate is 0.68 (P = .043). This represents a reduction in overall benefit with longer follow-up compared with the first 2 years (relative death rate of 0.52). Toxicity, particularly neurotoxicity, is still evident in the fourth year (10/31 on HD compared with 1/24 on LD). CONCLUSION: Our recommended dose of cisplatin in combination schedule is therefore 75 mg/m2, representing the optimal balance between efficacy and toxicity.

Effective destruction of cervical intraepithelial neoplasia (CIN) 3 at 100 degrees C using the Semm cold coagulator: 14 years experience.

A total of 1628 women with CIN 3 treated with the Semm cold coagulator between 1975 and 1989 was followed primarily by cytology. The standard suitability criteria for ablation were adhered to except that patients were treated at their first visit when the colposcopist expected that the diagnosis would be no worse than CIN 3. Overall 97% of the women were treated at their first visit. In 30 women (2%) the histology was glandular or worse than expected, but 22 of these showed no persistent cervical disease subsequently. Follow-up was achieved for 87% at 10 years. In actuarial terms the primary success rate was 95% at 1 year and 92% at 5 years, it was similar for all age groups. Repeat cold-coagulation for persistent/recurrent CIN 3 was less successful and is not advised. The outcome for 226 pregnancies established after treatment is known. The rates for miscarriage, preterm or operative delivery were not increased. Cold-coagulation of CIN 3 at 100 degrees C as performed by us is as effective as any other treatment and calls into question the need for more expensive practices.

Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer.

Cisplatin is generally accepted to be the most active cytotoxic agent for the treatment of ovarian cancer but the optimum dose remains unclear. We have performed a randomised trial to assess the importance of cisplatin dose in the treatment of advanced epithelial ovarian cancer. Patients were randomly assigned treatment with 50 mg/m2 (low dose) or 100 mg/m2 (high dose) cisplatin plus 750 mg/m2 cyclophosphamide, for a maximum of six cycles with intervals of 3 weeks. We planned to recruit 300 patients, but an interim analysis on the first 165 indicated a highly significant survival difference (p = 0.0008). Recruitment was therefore stopped and the trial patients were followed-up for 12 months longer. The relative progression rate (high-dose/low-dose) after 12 months' extra follow-up was 0.55 (95% confidence interval 0.37-0.81, p = 0.003) and the relative death rate 0.53 (0.34-0.81, p = 0.003). Overall median survival was 69 weeks in the low-dose group and 114 weeks in the high-dose group. Residual disease extent before chemotherapy had an important influence--patients with lesions of less than 2 cm did best; if given high-dose cisplatin their median survival was 3 years. 56 low-dose and 45 high-dose patients completed six cycles of chemotherapy; 15 and 9 patients, respectively, were withdrawn early because of progressive disease and treatment was stopped in 6 and 25, respectively, because of unacceptable side-effects or patient refusal. Toxic effects were significantly greater in the high-dose group, especially those on the nervous system and ears, alopecia, vomiting, and anaemia. Although the higher dose of cisplatin clearly leads to better results in terms of survival, its overall clinical benefit in the management of ovarian cancer will depend on further improvements in measures to alleviate toxic effects.