James D. Myles

PURPOSE: To determine the significance to patients of changes in health-related quality-of-life (HLQ) scores assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). PATIENTS AND METHODS: A subjective significance questionnaire (SSQ), which asks patients about perceived changes in physical, emotional, and social functioning and in global quality of life (global QL) and the QLQ-C30 were completed by patients who received chemotherapy for either breast cancer or small-cell lung cancer (SCLC). In the SSQ, patients rated their perception of change since the last time they completed the QLQ-C30 using a 7-category scale that ranged from "much worse" through "no change" to "much better." For each category of change in the SSQ, the corresponding differences were calculated in QLQ-C30 mean scores and effect sizes were determined. RESULTS: For patients who indicated "no change" in the SSQ, the mean change in scores in the corresponding QLQ-C30 domains was not significantly different from 0. For patients who indicated "a little" change either for better or for worse, the mean change in scores was about 5 to 10; for "moderate" change, about 10 to 20; and for "very much" change, greater than 20. Effect sizes increased in concordance with increasing changes in SSQ ratings and QLQ-C30 scores. CONCLUSION: The significance of changes in QLQ-C30 scores can be interpreted in terms of small, moderate, or large changes in quality of life as reported by patients in the SSQ. The magnitude of these changes also can be used to calculate the sample sizes required to detect a specified change in clinical trials.

PURPOSE: To determine the relative efficacy of an intensive cyclophosphamide, epirubicin, and fluorouracil (CEF) adjuvant chemotherapy regimen compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive breast cancer. PATIENTS AND METHODS: Premenopausal women with node-positive breast cancer were randomly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14; methotrexate 40 mg/m2 intravenously (i.v.) days 1 and 8; and fluorouracil 600 mg/m2 i.v. days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14; epirubicin 60 mg/m2 i.v. days 1 and 8; and fluorouracil 500 mg/m2 i.v. days 1 and 8. Each cycle was administered monthly for 6 months. Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy. RESULTS: The median follow-up was 59 months. One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients. The corresponding 5-year relapse-free survival rates were 53% and 63%, respectively (P = .009). One hundred seven CMF patients died compared with 85 CEF patients. The corresponding 5-year actuarial survival rates were 70% and 77%, respectively (P = .03). The rate of hospitalization for febrile neutropenia was 1.1% in the CMF group compared with 8.5% in the CEF group. There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group. Acute leukemia occurred in five patients in the CEF group. CONCLUSION: The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer.

PURPOSE: To determine the effect of intravenous (IV) low-osmolality iodinated contrast material (LOCM) on the development of post-computed tomography (CT) acute kidney injury (AKI), stratified by pre-CT estimated glomerular filtration rate (eGFR), in patients with stable renal function. MATERIALS AND METHODS: Institutional review board approval was obtained and patient consent waived for this HIPAA-compliant, retrospective study. CT examinations performed over a 10-year period on unique adult inpatients with sufficient serum creatinine (SCr) data and stable renal function (difference between baseline and pre-CT SCr within 0.3 mg/dL and 50% of baseline) were identified. A 1:1 propensity score matched cohort analysis with multivariate analysis of effects was performed with post-CT AKI as the primary outcome measure (8826 nonenhanced and 8826 IV contrast agent-enhanced CT studies in 17 652 patients). Propensity matching was performed with respect to likelihood of receiving IV contrast material (19 tested covariates). Post-CT AKI with Acute Kidney Injury Network SCr criteria was the primary endpoint. A stepwise multivariate conditional logistic regression model was performed to identify the effect of IV LOCM on post-CT AKI. RESULTS: After 1:1 propensity matching, IV LOCM had a significant effect on the development of post-CT AKI (P = .04). This risk increased with decreases in pre-CT eGFR (≥ 60 mL/min/1.73 m(2): odds ratio, 1.00; 95% confidence interval: 0.86, 1.16; 45-59 mL/min/1.73 m(2): odds ratio, 1.06; 95% confidence interval: 0.82, 1.38; 30-44 mL/min/1.73 m(2): odds ratio, 1.40; 95% confidence interval: 1.00, 1.97; <30 mL/min/1.73 m(2): odds ratio, 2.96; 95% confidence interval: 1.22, 7.17). CONCLUSION: IV LOCM is a nephrotoxic risk factor in patients with a stable eGFR less than 30 mL/min/1.73 m(2), with a trend toward significance at 30-44 mL/min/1.73 m(2). IV LOCM does not appear to be a nephrotoxic risk factor in patients with a pre-CT eGFR of 45 mL/min/1.73 m(2) or greater.

PURPOSE: To determine the significance to patients of changes in health-related quality-of-life (HLQ) scores assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). PATIENTS AND METHODS: A subjective significance questionnaire (SSQ), which asks patients about perceived changes in physical, emotional, and social functioning and in global quality of life (global QL) and the QLQ-C30 were completed by patients who received chemotherapy for either breast cancer or small-cell lung cancer (SCLC). In the SSQ, patients rated their perception of change since the last time they completed the QLQ-C30 using a 7-category scale that ranged from "much worse" through "no change" to "much better." For each category of change in the SSQ, the corresponding differences were calculated in QLQ-C30 mean scores and effect sizes were determined. RESULTS: For patients who indicated "no change" in the SSQ, the mean change in scores in the corresponding QLQ-C30 domains was not significantly different from 0. For patients who indicated "a little" change either for better or for worse, the mean change in scores was about 5 to 10; for "moderate" change, about 10 to 20; and for "very much" change, greater than 20. Effect sizes increased in concordance with increasing changes in SSQ ratings and QLQ-C30 scores. CONCLUSION: The significance of changes in QLQ-C30 scores can be interpreted in terms of small, moderate, or large changes in quality of life as reported by patients in the SSQ. The magnitude of these changes also can be used to calculate the sample sizes required to detect a specified change in clinical trials.

PURPOSE: This phase III study was performed to determine the superiority of doxorubicin (DOX) and vinorelbine (VNB) (arm 1) versus DOX alone (arm 2) in metastatic breast cancer (MBC) for overall survival (OS), time to treatment failure (TTF), toxicity, and quality of life (QOL). PATIENTS AND METHODS: Three hundred three patients were randomized to DOX 50 mg/m 2 intravenously (IV) on day 1 and VNB 25 mg/m 2 IV on days 1 and 8 (arm 1) or DOX 70 mg/m 2 IV on day 1 (arm 2). Both regimens were given every 3 weeks until a cumulative DOX dose of 450 mg/m 2 . After 16 of the first 65 randomized patients experienced febrile neutropenia (FN), the doses were reduced to DOX 40 mg/m 2 on day 1 and VNB 20 mg/m 2 on days 1 and 8 versus DOX 60 mg/m 2 on day 1. Eligible patients were vinca alkaloid and anthracycline naive. Chemotherapy was first-line or second-line for MBC. RESULTS: Three patients were ineligible. Thus, 300 patients were assessable for toxicity and to determine time to disease progression (TTP), TTF, and OS. Two hundred eighty-nine patients were assessable for response, and 99 responders were assessable for response duration (RD). The response rates, QOL, and median RD, TTP, and TTF were not significantly different between the arms. Median OS was 13.8 months for arm 1 versus 14.4 months for arm 2 (P = .4). Grade 3 or 4 granulocytopenia was equivalent in both arms but more grade 3/4 neurotoxicity, mild venous toxicity, and FN were seen on arm 1. CONCLUSION: The survival with DOX and VNB is not superior to DOX alone in MBC.