Objective:This study investigated the prognostic significance of age at diagnosis, stage, tumor subtype, pelvic lymph node metastasis (PLNM), lymph-vascular space involvement (LVSI), presence or absence of deep cervical stromal invasion (DCSI) in stage ⅠB-ⅡA cervical cancer patients. It also investigated the inter-relationship among these factors. Methods: 152 patients treated with radical hysterectomy plus pelvic lymphadenectomy were followed up for a median of 49 months and were evaluated retrospectively. Results: The 5-year overall survival rate was 84.8%. The distribution of age at diagnosis is of bimodal shape, peaking at 42 and 68 years, respectively. Tumor subtype, PLNM, DCSI, and LVSI were found to be significant prognostic factors individually. After multivariate analysis, only tumor subtype and PLNM were found to be independent, significant prognostic factors for survival. The prognostic importance of LVSI appeared to be eclipsed by the presence of PLNM. DCSI was statistically related with FIGO stage, LVSI and PLNM. Conclusion: Tumor subtype and PLNM are the two most important independent prognostic factors for stages ⅠB-ⅡA cervical cancer. Some prognostic factors are inter-related and may reflect different facets of tumor progression.
Objective:To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice.Methods: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg×2, 3.0 mg/kg×2, 6.0 mg/kg×2 or 10.0 mg/kg×1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg×2 or 10.0 mg/kg×1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis.Results: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation.Conclusion:The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.
