ABSTRACT
PURPOSE: This article presents the long-term results of the international multicenter randomized trial that investigated the use of neoadjuvant cisplatin, methotrexate, and vinblastine (CMV) chemotherapy in patients with muscle-invasive urothelial cancer of the bladder treated by cystectomy and/or radiotherapy. Nine hundred seventy-six patients were recruited between 1989 and 1995, and median follow-up is now 8.0 years. PATIENTS AND METHODS: This was a randomized phase III trial of either no neoadjuvant chemotherapy or three cycles of CMV. RESULTS: The previously reported possible survival advantage of CMV is now statistically significant at the 5% level. Results show a statistically significant 16% reduction in the risk of death (hazard ratio, 0.84; 95% CI, 0.72 to 0.99; P = .037, corresponding to an increase in 10-year survival from 30% to 36%) after CMV. CONCLUSION: We conclude that CMV chemotherapy improves outcome as first-line adjunctive treatment for invasive bladder cancer. Two large randomized trials (by the Medical Research Council/European Organisation for Research and Treatment of Cancer and Southwest Oncology Group) have confirmed a statistically significant and clinically relevant survival benefit, and neoadjuvant chemotherapy followed by definitive local therapy should be viewed as state of the art, as compared with cystectomy or radiotherapy alone, for deeply invasive bladder cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Muscle Neoplasms/drug therapy , Neoadjuvant Therapy/methods , Urinary Bladder Neoplasms/drug therapy , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cisplatin/therapeutic use , Female , Humans , Kaplan-Meier Estimate , Male , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Middle Aged , Muscle Neoplasms/secondary , Neoplasm Invasiveness , Neoplasm Staging , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Vinblastine/administration & dosage , Vinblastine/therapeutic useABSTRACT
BACKGROUND: Women who are positive for thyroid antibodies in early gestation are prone to post-partum depression, apparently independent of thyroid dysfunction, as measured by serum levels of free thyroxine, free triodothyroxine and thyroid-stimulating hormone. This finding may be due to infrequent monitoring of thyroid function, because hyperthyroidism, hypothyroidism and combinations of both may occur post-partum. AIMS: To test the hypothesis that stabilising thyroid function post-partum by administering daily thyroxine reduces the rate of occurrence and severity of associated depression. METHOD: In a randomised double-blind placebo-controlled trial, 100 microg of thyroxine or placebo was given daily to 446 thyroid-antibody-positive women (342 of whom were compliant) from 6 weeks to 6 months post-partum, assessing their psychiatric and thyroid status at 4-weekly intervals. RESULTS: There was no evidence that thyroxine had any effect on the occurrence of depression. The 6-month period prevalence of depression was similar to that reported previously. CONCLUSIONS: The excess of depression in thyroid-antibody-positive women in the post-partum period is not corrected by daily administration of thyroxine.
