Carol M. Moinpour

Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of Patients With Advanced Non–Small-Cell Lung Cancer: A Southwest Oncology Group Trial

PURPOSE This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non--small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS Two hundred two patients received VC (vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m(2) over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P =.002) and neutropenia (P =.008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P =.001, P =.007), and grade 3 peripheral neuropathy was higher on the PC arm (P <.001). More patients on the VC arm discontinued therapy because of toxicity (P =.001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.

Quality of life in survivors of colorectal carcinoma

Colon carcinoma is a common malignancy that accounts for a substantial share of all cancer‐related morbidity and mortality. However, little is known with regard to general and disease specific quality of life in survivors of colorectal carcinoma, particularly from community‐based samples of cases across stage and survival times from diagnosis.

Intermittent versus Continuous Androgen Deprivation in Prostate Cancer

BACKGROUND Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. METHODS Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization. RESULTS A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events. CONCLUSIONS Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).

A randomized clinical trial of home nursing care for lung cancer patients

A randomized clinical trial was conducted to assess the effects of home nursing care for patients with progressive lung cancer. One hundred sixty‐six patients were assigned to either an oncology home care group (OHC) that received care from oncology home care nurses, a standard home care group (SHC) that received care from regular home care nurses, or an office care group (OC) that received whatever care they needed except for home care. Patients were entered into the study 2 months after diagnosis and followed for 6 months. Patients were interviewed at 6‐week intervals across five occasions. At the end of the study, there were no differences in pain, mood disturbance, and concerns among the three groups. There were significant differences in symptom distress, enforced social dependency, and health perceptions. The two home nursing care groups had less distress and greater independence 6 weeks longer than the office care group. In addition, the two home nursing care groups steadily reported worse health perceptions over time. Thus, it was remarkable that the office care group, which indicated more symptom distress and social dependency with time, also indicated perceptions of improved health with time. These results suggest that home nursing care assists patients with forestalling distress from symptoms and maintaining their independence longer in comparison to no home nursing care. Home care may also include assisting patients in acknowledging the reality of their situation.

Quality of life in long term survivors of colorectal cancer

Abstract OBJECTIVES: We aimed to determine the quality of life (QOL) for long term survivors of colorectal cancer. METHODS: Persons with colorectal cancer who had survived at least 5 yr from diagnosis were recruited from a local cancer registry to answer questions about general QOL and colon cancer-specific issues. Before the general survey, focus group interviews with long term survivors were conducted to select survey questions from a pool of general and cancer-specific QOL questionnaires. The survey included the Health Utilities Index, the Center for Epidemiological Studies Depression Scale, and questions from the Short Form 36 and Functional Assessment of Cancer Therapy-Colorectal Cancer. After permission was obtained from their primary physicians, long term survivors from the registry were mailed invitation letters, then telephoned. Those agreeing were mailed self-administered questionnaires with stamped return envelopes. RESULTS: Two hundred twenty-seven respondents (average age = 74 yr, 46% female) completed the survey. Survivors reported a relatively uniform and high QOL, irrespective of stage at diagnosis and time from diagnosis. Non-cancer related comorbid conditions and low income status had more influence on overall QOL than initial stage of colorectal cancer or time since diagnosis. Compared to age-matched populations, long term survivors reported higher overall QOL, but had higher rates of depression. Sixteen percent reported three or more bowel movements a day; 49% reported chronic recurrent diarrhea. CONCLUSIONS: Those who achieve long term remission from colorectal cancer may experience a relatively high QOL, although physical symptoms such as diarrhea and depressive symptoms remain a problem.

The use of patient-reported outcomes (PRO) within comparative effectiveness research: implications for clinical practice and health care policy.

Background:The goal of comparative effectiveness research (CER) is to explain the differential benefits and harms of alternate methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. To inform decision making, information from the patient’s perspective that reflects outcomes that patients care about are needed and can be collected rigorously using appropriate patient-reported outcomes (PRO). It can be challenging to select the most appropriate PRO measure given the proliferation of such questionnaires over the past 20 years. Objective:In this paper, we discuss the value of PROs within CER, types of measures that are likely to be useful in the CER context, PRO instrument selection, and key challenges associated with using PROs in CER. Methods:We delineate important considerations for defining the CER context, selecting the appropriate measures, and for the analysis and interpretation of PRO data. Emerging changes that may facilitate CER using PROs as an outcome are also reviewed including implementation of electronic and personal health records, hospital and population-based registries, and the use of PROs in national monitoring initiatives. The potential benefits of linking the information derived from PRO endpoints in CER to decision making is also reviewed. Conclusions:The recommendations presented for incorporating PROs in CER are intended to provide a guide to researchers, clinicians, and policy makers to ensure that information derived from PROs is applicable and interpretable for a given CER context. In turn, CER will provide information that is necessary for clinicians, patients, and families to make informed care decisions.

Assessing Meaningful Change in Quality of Life Over Time: A Users' Guide for Clinicians

The objective of this article is to help clinicians interpret trial-based quality of life (QOL) changes over time. We address a series of questions and provide guidelines that are fundamental to assessing and interpreting change. The issues addressed are as follows: (1) What are the characteristics of the population for whom changes in QOL are reported? (2) Is the QOL questionnaire reliable, valid, and responsive to change? (3) Are the timing and frequency of assessments adequate? (4) Is the study adequately powered? (5) How are multiple QOL outcomes addressed in analyses? (6) How are multiple time points handled? (7) Can alternative explanations account for the observed change or lack of observed change (eg, handling of missing data, survival differences, and changes in patients QOL perspective over time)? and (8) How is statistical significance translated into meaningful change? These guidelines will support clinicians in reviewing the clinical trial literature, which in turn can help them use the data in the treatment decision process.

Health-Related Quality of Life Results in Pathologic Stage C Prostate Cancer From a Southwest Oncology Group Trial Comparing Radical Prostatectomy Alone With Radical Prostatectomy Plus Radiation Therapy

PURPOSE To compare short- and long-term effects of adjuvant treatment versus observation after surgery on health-related quality of life (HRQL) of prostate cancer patients. PATIENTS AND METHODS The Southwest Oncology Group (SWOG) intergroup trial compared radical prostatectomy (RP) plus observation versus RP plus adjuvant radiation therapy (RT). Two-hundred seventeen of 425 therapeutic trial patients were eligible and registered to the HRQL study. Patients completed the SWOG Quality of Life Questionnaire (emotional, physical, social, and role function; general symptom status; treatment/disease-specific symptoms; and global HRQL [GHRQL]) at baseline, 6 weeks, 6 months, and annually for 5 years. Prespecified outcomes were three genitourinary symptoms (bowel function tenderness, frequent urination, and erectile dysfunction [ED]) and measures of physical and emotional function. Adjustments were made for the baseline score. RESULTS Patients receiving adjuvant RT reported worse bowel function (through approximately 2 years) and worse urinary function. There were no statistically significant differences for ED. GHRQL was initially worse for the RP+RT arm but improved over time and was better at the end of the period than the GHRQL reported for RP alone (treatment arm x time interaction, P = .0004). Symptom distress was significantly worse for the RP+RT arm compared with the RP alone arm, but the treatment arms did not differ with respect to other general measures of HRQL. CONCLUSION The addition of RT to surgery resulted in more frequent urination, as well as early report of more bowel dysfunction, although bowel function differences disappeared over the 5-year period. The addition of RT did not negatively impact ED.

The clinical significance of quality of life assessments in oncology: a summary for clinicians

BackgroundA series of six manuscripts with an introduction appeared in the Mayo Clinic Proceedings, based upon the collective effort of 30 individuals with an interest and expertise in assessing the clinical significance of quality of life (QOL) assessments. The series of manuscripts described the state of the science of QOL assessments in oncology clinical research and practice and included extensive literature and theoretical justification for the continued inclusion of QOL in oncology clinical research and practice.ObjectivesThe purpose of this paper is to produce a summary of these articles and to supplement these works with additional information that was gleaned from subsequent meetings and discussions of this material. The primary aim of this paper is to present a cogent and concise description for clinicians to facilitate the incorporation of QOL assessments into oncology clinical research and practice. The theoretical discussion is supplemented with an example of how the various ideas can be operationalized in an oncology clinical trial.

Report from a National Cancer Institute (USA) workshop on quality of life assessment in cancer clinical trials.

To promote the inclusion of quality of life (QOL) end-points in clinical research on cancer, the National Cancer Institute (USA) sponsored a workshop on QOL assessment in cancer clinical trials in July, 1990. Experts in clinical trials and QOL research formed four working groups to identify current areas of cancer treatment in which QOL end-points are most important; to discuss methodologic problems in QOL assessment; to address common problems in implementing clinical studies with QOL end-points; and to consider statistical issues in design, implementation, and data analysis. Recommendations made by the working groups are summarized in this paper.