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|Research Update on PARP Inhibition: Emerging Data in Breast, Ovarian, and Other Cancers|
In this Interactive Virtual Presentation, William J. Gradishar, MD, FACP, reviews the mechanism of PARP inhibition and its rationale as a therapeutic pathway and describes recent data using novel PARP inhibitors.
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Int J Gynecol Cancer. 2010 May;20(4):664-684.
*Psycho-oncology Co-operative Research Group, School of Psychology, daggerCentre for Medical Psychology and Evidence-Based Decision-Making (CeMPED), University of Sydney, Sydney, New South Wales, Australia; double daggerDepartment of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia; section signAustralia New Zealand Gynaecological Oncology Group (ANZGOG), Sydney, New South Wales, Australia; and parallelSchool of Psychology, University of Sydney, Sydney, New South Wales, Australia.
OBJECTIVES:: Researchers wishing to assess the health-related quality of life (HRQoL) of women with gynecologic cancers have a range of questionnaires to choose from. In general, disease-, treatment-, or symptom-specific questionnaires are assumed to be better able to identify between-group differences (sensitivity) and changes over time (responsiveness) than are cancer-specific or generic questionnaires. However, little work has tested this assumption in oncology. We set out to (a) identify all multidimensional HRQoL questionnaires used in studies with women with gynecologic cancer and (b) evaluate their track records in identifying minimal clinically important differences (MCIDs), with a view to making recommendations. METHODS:: We searched MEDLINE using the term quality of life and each gynecologic cancer type, as well as the names of identified questionnaires. We used 10% of the scale range as the threshold for an MCID. RESULTS:: We identified 1 generic (SF-36/SF-12), 3 cancer-specific (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ] C30, Functional Assessment of Cancer Therapy-General [FACT-G], and short-form Cancer Rehabilitation Evaluation System [CARES-SF]), and 1 disease-specific (QOL-Ovarian Cancer Patient Version) HRQoL questionnaires and 5 disease-specific (QLQ-OV28, FACT-O for ovarian, QLQ-CX24, FACT-Cx for cervical and FACT-V for vulvar), 1 treatment-specific (FACT and Gynecologic Oncology Group-Ntx for neurotoxicity), and 2 symptom-specific (FACT-Anemia and Functional Assessment of Chronic Illness and Therapy [FACIT]-Fatigue) modules. Twenty-seven articles reported results from 26 studies in which an MCID had been identified. The FACIT's anemia and fatigue subscales were more sensitive, and the neurotoxicity subscale more sensitive and responsive than the FACT-G on at least 1 comparison. However, we found no evidence for superior performance by the FACT-G compared with the SF-36 or EORTC and FACIT disease-specific modules versus the QLQ-C30 and FACT-G. There was also little evidence to favor EORTC versus FACIT questionnaires or vice versa. CONCLUSIONS:: The evidence we reviewed offered little support for the hypothesis that disease-, symptom-, or treatment-specific instruments are more sensitive and responsive than cancer-specific or generic questionnaires. However, conclusions were limited by the small number of head-to-head comparisons available. We summarize the clinical contexts in which each instrument identified an MCID to inform choice of questionnaire(s), sample size calculations, and interpretation of results in future studies.
Affiliations of authors: Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands (BT); Medisch Centrum Rijnmond Zuid, Rotterdam, the Netherlands (PT); EORTC Data Centre, Brussels, Belgium (PT, CC, KV, AC); Department of Obstetrics and Gynaecology, University of Brescia, Brescia, Italy (SP); Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands (MvdB); Department of Medical Oncology, Hospital Universitario San Carlos, Madrid, Spain (AC)
Correspondence to: Baptist Trimbos, MD, PhD, Department of Gynecology, Leiden University Medical Center, POB 9600, 2300RC Leiden, the Netherlands (e-mail: email@example.com).
A long-term follow-up analysis of the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm (ACTION) from the European Organization for Research and Treatment of Cancer was undertaken to determine whether the original results with a median follow-up of 5.5 years could be verified after longer follow-up with more events. In the ACTION trial, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation (no further treatment). The original analysis found that adjuvant chemotherapy improved recurrence-free survival but not overall survival and found in a subgroup analysis that completeness of surgical staging was an independent prognostic factor, with better recurrence-free and overall survival among those with complete (optimal) surgical staging. After a median follow-up of 10.1 years, we analyzed the more mature data from the ACTION trial and found support for most of the main conclusions of the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy (hazard ratio of death = 1.89, 95% confidence interval = 0.99 to 3.60; overall two-sided log-rank test P = .05). More cancer-specific deaths were observed among nonoptimally staged patients (40 [27%] of the 147 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) than among optimally staged patients (seven [9%] of the 75 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) (two-sided 2 test for heterogeneity, P = .06). Thus, completeness of surgical staging in patients with early ovarian cancer was found to be statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy appeared to be restricted to patients with nonoptimal surgical staging.
|CONTEXT AND CAVEATS|
In the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation. After a median follow-up of 5.5 years, adjuvant chemotherapy was associated with improved recurrence-free survival but not overall survival. In a subgroup analysis, better recurrence-free and overall survival were observed among those with nonoptimal surgical staging than those with optimal staging.
Long-term analysis of data from this trial after a median of 10.1 years of follow-up.
The long-term analysis supported most conclusions from the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy. More cancer-specific deaths were observed among nonoptimally staged patients than among optimally staged patients.
Completeness of surgical staging among patients with early ovarian cancer was statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy was restricted to patients with nonoptimal surgical staging.
The trial was not designed to compare different surgical staging procedures. Patients could not be prospectively stratified by surgical staging category. The study had a limited sample size. Quality of life was not studied.
From the Editors
• Pressure, discomfort or pain in the pelvis, abdomen, back, or legs
• Gas, bloating, indigestion or abdominal distension
• Early satiety or feeling full even if you haven't eaten much
• Nausea, vomiting, loss of appetite or weight loss
• A change in the pattern of urination
• Abnormal vaginal bleeding, including abnormal menstrual periods