BACKGROUNDDoxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin‐related congestive heart failure (CHF) after a cumulative dose of 550 mg/m2. To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs.METHODSA group of 630 patients who were randomized to a doxorubicin‐plus‐placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis.RESULTSThirty‐two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin‐related CHF at a cumulative dose of 550 mg/m2. Age appeared to be an important risk factor for doxorubicin‐related CHF after a cumulative dose of 400 mg/m2, with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age ≤ 65 years). In addition, > 50% of the patients who experienced doxorubicin‐related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study.CONCLUSIONSDoxorubicin‐related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin. Cancer 2003;97:2869–79. © 2003 American Cancer Society.DOI 10.1002/cncr.11407

BACKGROUND. Health care databases provide a widely used source of data for health care research, but their accuracy remains uncertain. We analyzed data from the 1985 National DRG Validation Study, which carefully reabstracted and reassigned ICD-9-CM diagnosis and procedure codes from a national sample of 7050 medical records, to determine whether coding accuracy had improved since the Institute of Medicine studies of the 1970s and to assess the current coding accuracy of specific diagnoses and procedures. METHODS. We defined agreement as the proportion of all reabstracted records that had the same principal diagnosis or procedure coded on both the original (hospital) record and on the reabstracted record. We also evaluated coding accuracy in 1985 using the concepts of diagnostic test evaluation. RESULTS. Overall, the percentage of agreement between the principal diagnosis on the reabstracted record and the original hospital record, when analyzed at the third digit, improved from 73.2% in 1977 to 78.2% in 1985. However, analysis of the 1985 data demonstrated that the accuracy of diagnosis and procedure coding varies substantially across conditions. CONCLUSIONS. Although some diagnoses and all major surgical procedures that we examined were accurately coded, the variability in the accuracy of diagnosis coding poses a problem that must be overcome if claims-based research is to achieve its full potential.

Limited data are available on the relation between physical fitness and mortality from cardiovascular disease. We examined this question in a study of 4276 men, 30 to 69 years of age, whom we followed for an average of 8.5 years. Examinations at base line included assessment of conventional coronary risk factors and treadmill exercise testing. The heart rate during submaximal exercise (stage 2 of the exercise test) and the duration of exercise were used as measures of physical fitness. Men with incomplete data (n = 308) or who were using cardiovascular drugs (n = 213) were excluded from the analysis. Men who had clinical evidence of cardiovascular disease at base line (n = 649) were analyzed separately. Forty-five deaths from cardiovascular causes occurred among the remaining 3106 men. A lower level of physical fitness was associated with a higher risk of death from cardiovascular and coronary heart disease, after adjustment for age and cardiovascular risk factors. The relative risk of death from cardiovascular causes was 2.7 (95 percent confidence interval, 1.4 to 5.1; P = 0.003) for healthy men with an increment of 35 beats per minute in the heart rate during stage 2, and 3.0 (95 percent confidence interval, 1.6 to 5.5; P = 0.0004) for those with a decrement of 4.4 minutes in the exercise time spent on the treadmill. The corresponding values for death from coronary heart disease were 3.2 (95 percent confidence interval, 1.5 to 6.7; P = 0.003) and 2.8 (95 percent confidence interval, 1.3 to 6.1; P = 0.007), respectively. We conclude that a lower level of physical fitness is associated with a higher risk of death from coronary heart disease and cardiovascular disease in clinically healthy men, independent of conventional coronary risk factors.

DZR had a significant cardioprotective effect as measured by noninvasive testing and clinical CHF. One of the two studies (088001) showed a lower response rate with DZR, but time to progression and survival were not significantly different. DZR is the first agent shown to reduce cardiotoxicity from doxorubicin.

We conclude that substituting telephone care for selected clinic visits significantly reduces utilization of medical services. For more severely ill patients, the increased contact made possible by telephone care may also improve health status and reduce mortality.