Notes: Objective To study whether intervention debulking surgery improves survival in patients with advanced ovarian cancer who have bulky (〉 2 cm) residual disease after primary surgery.Design A prospective multicentre randomised study.Setting Hospitals in the West Midlands.Subjects Ovarian cancer patients with bulky residual disease after primary surgery who are considered well enough to receive cis-platinum based chemotherapy and further surgery.Methods Eligible patients were randomised to receive combination chemotherapy alone or combined with intervention debulking surgery.Main outcome measure Survival was assessed using product limit method and log-rank test.Results Seventy-nine patients were entered into the study. Thirty-seven patients were randomised to intervention debulking surgery, 25 (67%) of whom underwent intervention debulking surgery, which was performed a median of 13 weeks after primary surgery. The median survival for the intervention debulking surgery group was 15 months (95% CI 10–20 mo) and that of those randomised to chemotherapy alone, which was 12 months (95% CI 8–16 mo), were not significantly different (hazard ratio = 0.71; 95% CI 0.44–1.13).Conclusion Intervention debulking surgery may not improve survival in patients with advanced ovarian cancer.

Notes: Summary Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy. Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy, but many patients are treated with radical radiotherapy. At present there is no method of accurately identifying patients at high risk of recurrence in the latter group. A retrospective analysis of 141 surgically managed cases with state I/IIa cervical cancer is presented. The study aims were to characterize patients at high risk of relapse, identify independent prognostic variables predicting for relapse and, using these variables, develop a model, that would accurately predict high-risk patients. Univariate analysis identified depht of invasion, substage, lymph node involvement, lymphatic and blood vessel invasion and tumour differentiation as significant prognostic variables. After stratification for depth of invasion, which did not conform to the proportional hazards assumption implicit in the Cox model, Cox regression analysis showed substage, lymphatic and vascular invasion and histological tumour type to be independent prognostic variables. Using these variables, classification models were constructed that would be applicable to patients treated with either surgery or radiotherapy. Applying the models to 110 cases with 〉18 months follow-up, 11/18 (61%) and 11/19 cases (58%) predicted as being at high risk of relapse have developed recurrence. Highly active chemotherapy is now available for this disease. We have demonstrated that combined bleomycin, ifosfamide and cisplatin (BIP) is one of the most active regimens in this disease. BIP produces cytoreduction in around 70% of patients with recurrent and primary advanced disease. Responses are achieved rapidly and acute radiotherapy toxicity is not enhanced by giving chemotherapy prior to radical local radiotherapy. A multicentre, prospective randomized trial testing the role of BIP as adjuvant therapy in patients with positive nodes at radical hysterectomy is now in progress. A complementary study testing the role of adjuvant chemotherapy in high-risk patients treated with radical radiotherapy is in preparation.

Notes: Summary The cytotoxic drug mitozolomide has been found to cause unpredictably severe thrombocytopenia during phase I and II clinical trials. In an attempt to relate dose and pharmacokinetic parameters to toxicity, we measured plasma concentrations of mitozolomide in 14 patients with a range of malignancies. There were significant correlations (Spearman rank correlation test) between drug clearance and AUC and white blood cell nadir. The pharmacokinetic and toxicity data were not normally distributed; therefore, it was not possible to construct predictive nomograms for toxicity based on linear regression analysis.