A randomised study of carboplatin vs sequential ifosfamide/carboplatin for patients with FIGO stage III epithelial ovarian carcinoma

In a study designed to compare response rates of patients with stage III epithelial ovarian carcinoma to ifosfamide and carboplatin, 152 patients were randomised to receive either sequential therapy with three cycles of ifosfamide followed by three cycles of carboplatin, or to six cycles of single agent carboplatin. Ifosfamide was given every 3 weeks in a dose of 5 gm m-2 as a 24 h infusion with mesna, 1 gm m-2 by i.v. bolus prior to ifosfamide, 3 gm m-2 with ifosfamide, and 1 gm m-2 as an 8 h infusion after ifosfamide. Carboplatin was given in a dose of 400 mg m-2 by short i.v. infusion every 4 weeks. Sixty-eight evaluable patients were randomised to sequential ifosfamide/carboplatin, and 67 to single agent carboplatin. Median follow-up is 36 months (range 5.5-82.3). After three cycles of treatment two patients in the ifosfamide/carboplatin arm achieved complete remission (CR), and 12 partial remission (PR) for an overall response rate of 29%, whereas in the carboplatin arm ten patients achieved CR, and 23 PR, for an overall response rate of 63% (P = 0.0008). Seven of 15 patients with progressive disease, and nine of 20 patients with stable disease at the initial response evaluation, following three cycles of ifosfamide, subsequently responded to carboplatin therapy so that the final response rate to the complete regimen was 65% for the ifosfamide/carboplatin arm, compared to 71% for the carboplatin arm (NS). For the ifosfamide/carboplatin arm, median recurrence free survival and overall survival were 14.1 months and 18.7 months. Corresponding figures for the carboplatin arm were 14.5 months and 21.5 months (NS). Both treatments were generally well tolerated. However 47% of patients in the ifosfamide/carboplatin arm developed alopecia sufficient to require a wig, compared to only 2% in the carboplatin arm. Ifosfamide is clearly less effective, and more toxic than carboplatin. Ifosfamide failures can however be effectively salvaged by subsequent carboplatin treatment. Ifosfamide cannot be recommended for single agent therapy in ovarian carcinoma, however the combination of carboplatin plus ifosfamide might be a suitable treatment to be tested in a future randomised study against carboplatin alone

Austin Clarke

This is the first book to examine the work of Austin Clarke (1896-1974) in the light of modern critical and theoretical perspectives. Clarke was one of Ireland's major writers whose career was devoted as much to fiction, drama and autobiography as to poetry. The study assesses Clarke's work in its entirety but focuses on key works which reveal how resourcefully Clarke explored themes such as the coherence of the personality, the inner lives of women and the roots of repression

The Internal Chemical Shift. A Key To Bonding In Aromatic Molecules. I. Internal Shift Correlations

The study of proton shift behavior in nine families of disubstituted benzenes has provided quantitative correlations of internal and meta shifts among all families. The equations of correlation are useful in the prediction of shifts to an error of 0.015 ppm. The studies demonstrate shift additivity for the 4-substituted halobenzenes and suggest a chain rule relationship for substituent effects in those compounds. For that reason, previous theories of substituent interactions involving inductive and resonance contributors appear incorrect when applied to proton shift data. In decreasing order of up field shift at the ortho protons the substituents studied include N(CH3)2, NH2, OCH3, OH, F, CH3, CH2CH3, H, Cl, C(CH3)3, Br, CN, COOCH3, COOH, COCI, NO2. © 1973, American Chemical Society. All rights reserved

Innovative financing for health: what are the options for South Africa?

The paper assesses the options for additional innovative financing that could be considered in South Africa, covering both raising new funds and linking funds to results. New funds could come from: i) the private sector, including the mining and mobile phone industry; ii) from voluntary sources, through charities and foundations; iii) and through further expanding health (sin) levies on products such as tobacco, alcohol and unhealthy food and drinks. As in other countries, South Africa could earmark some of these additional sources for investment in interventions and research to reduce unhealthy behaviors and influence the determinants of health. South Africa could also expand innovative linking of funds to improve overall performance of the health sector, including mitigating the risks for non-state investment and exploring different forms of financial incentives for providers and patients. All such innovations would require rigorous monitoring and evaluation to assess whether intended benefits are achieved and to look for unintended consequences