First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial)

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26–56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m−2 – doxorubicin (D) 75 mg m−2 cycle 1, C: 3 g m−2 – D: 75 mg m−2 cycle 2, C: 3 g m−2 – D: 75 mg m−2 – 5 FU 2500 mg m−2 cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4–1.04) and 0.96 (range 0.25–1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% ± 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3–9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% ± 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome. © 1999 Cancer Research Campaig

Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review

Being male or female is an important determinant of risks for certain diseases, patterns of illness and life expectancy. Although differences in risks for and prognoses of several diseases have been well documented, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. The objective of this umbrella review was to determine whether clinically relevant differences in efficacy and safety of commonly prescribed medications exist between men and women. We retrieved all available systematic reviews of the Oregon Drug Effectiveness Review Project published before January 2010. Two persons independently reviewed each report to identify relevant studies. We dually abstracted data from the original publications into standardized forms. We synthesized the available evidence for each drug class and rated its quality applying the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Findings, based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women. Some clinically important exceptions, however, were apparent: women experienced substantially lower response rates with newer antiemetics than men (45% vs. 58%; relative risk 1.49, 95% confidence interval 1.35–1.64); men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder; women discontinued lovastatin more frequently than men because of adverse events. Overall, for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment. The available body of evidence, however, was limited in quality and quantity, confining the range and certainty of our conclusions