Sixteen-week dose-intense chemotherapy in the adjuvant treatment of breast cancer.

Fifty-three women with breast cancer were treated with a new 16-week dose-intense, chemotherapy regimen. Patients with operable breast cancer with 10 or more histologically positive axillary nodes were treated with this five-drug regimen that incorporated the concepts of weekly chemotherapy, sequential administration of antimetabolites, and continuous infusion of fluorouracil (5-FU). The chemotherapy regimen consisted of eight cycles (each of 2 wk duration) of 100 mg of cyclophosphamide/m2 orally on days 1-7, 40 mg of doxorubicin/m2 intravenous (IV) on day 1, 100 mg of methotrexate/m2 IV on day 1 with 10 mg of leucovorin rescue/m2 every 6 hours for six oral doses on day 2, 1 mg of vincristine IV on day 1, and 600 mg of 5-FU/m2 IV at hour 20 over 2 hours. A continuous infusion of 300 mg of 5-FU/m2 per day was given IV on days 8-9 of each 2-week cycle. The doses and schedule of drug administration were designed to minimize dosage reduction and treatment delay. At a median follow-up of 17 months, there have been eight relapses in the 53 patients. The actuarial 3-year disease-free survival is 80% (95% confidence interval, 62% to 90%). The major side effects were attributable to myelosuppression. Absolute neutrophil counts less than 250/microL were noted in 12 (23%) patients; seven patients (13%) required hospitalization for management of neutropenic fever. No treatment-related deaths occurred. Ninety-four percent of the planned doses were administered, and only 5% of the courses were delayed because of toxic reactions. The encouraging therapeutic data, manageable side effects, and our ability to deliver over 90% of the planned doses provide the rationale for a phase III comparison of this new dose-intense regimen and standard chemotherapy in patients with operable disease and positive axillary nodes.

Effect of patients' expectations of benefit with standard breast cancer adjuvant chemotherapy on participation in a randomized clinical trial: a clinical vignette study.

Patients frequently overestimate the benefit of standard breast cancer adjuvant therapy. This is due in part to vague doctor-patient communication. To examine how the doctor's description and patient's expectations of the benefit of standard therapy affect clinical trial participation, we randomized 282 female cancer patients to one of two versions of a clinical vignette describing a choice between standard cyclophosphamide, methotrexate, and fluorouracil (5FU) (CMF) and a randomized trial comparing CMF with cyclophosphamide, doxorubicin, and 5FU (CAF). The vignettes differed only on whether results with CMF were described verbally or numerically in terms of disease-free survival (DFS). After selecting CMF or the trial, patients estimated their 10-year DFS with CMF. Patients were randomized 3:1 to the verbal vignette. The trial was selected by 110 of 210 (52.4%) verbal vignette patients versus 25 of 72 (34.7%) numeric vignette patients (P = .01). Estimates of 10-year DFS with CMF varied considerably; many were inaccurate. When patients in the verbal vignette group were divided into thirds according to DFS estimate, 22 of 64 (34.4%) in the top third selected the trial versus 38 of 64 (59.4%) and 38 of 65 (58.5%) in the middle and bottom third, respectively (P = .005). Younger age, college education, and previous participation in a trial also predicted trial selection. Multivariate logistic regression suggested that the benefit expected from CMF was more important than how benefit was described in treatment selection. Assuring realistic patient expectations of standard adjuvant therapy benefit is likely to be important during discussion of clinical trials.

Once-daily irrigation of long-term urethral catheters with normal saline. Lack of benefit.

Urinary incontinence is often managed with a long-term urethral catheter after other methods have failed. Such urethral catheterization is associated with polymicrobial bacteriuria, catheter obstruction, fever, bacteremia, urinary tract stones, and death. Periodic catheter irrigation is a common but untested management procedure intended to prevent catheter obstruction, fevers, and/or bacteremia. To evaluate this technique, we performed a randomized crossover trial comparing ten weeks of once-daily normal saline irrigation with ten weeks of no irrigation in 32 long-term catheterized women. The incidence of catheter obstructions and febrile episodes and the prevalence and species of bacteriuria were similar whether examined as completed crossover patients (N = 23) or as partially completed trials (N = 9). Once-daily irrigation with normal saline of long-term urethral catheters is a time-consuming and costly procedure that is unlikely to have an impact on the morbidity associated with such catheters.

Commonly used methods of estimating creatinine clearance are inadequate for elderly debilitated nursing home patients.

We evaluated the Jelliffe and the Cockcroft and Gault methods of estimating creatinine clearance in elderly nursing home patients (65 years) with chronic indwelling urethral catheters. Although these relationships have been prospectively validated in hospitalized and ambulatory populations previously, we found that they produced poor estimates of creatinine clearance in this patient group. For the Jelliffe method, 11 of 19 estimates were 20% or greater from the measured value; 10 of 11 poor estimates were high. The Cockcroft-Gault method had 10 of 19 estimates 20% or greater from the measured value with 8 of 10 of the poor estimates being high. An altered relationship between body weight, muscle mass, and daily creatinine production is the most likely explanation for the bias in these creatinine-clearance estimations. New estimates of the relationships between age, weight, serum creatinine, and creatinine clearance need to be developed for this population.

Do clinical microbiology laboratories report complete bacteriology in urine from patients with long-term urinary catheters?

Bacteriuria associated with long-term urinary catheters (those in place for greater than or equal to 30 days) appears to be the most common nosocomial infection in U.S. medical care facilities. This bacteriuria is polymicrobial and dynamic and accompanied by fevers, catheter obstructions, bacteremias, and deaths. We compared the reporting by our research laboratory of bacteria present in urine from long-term-catheterized nursing home patients with that by two commercial laboratories. The commercial laboratories isolated significantly fewer bacterial species at 10(5) CFU/ml of urine specimen. Organisms well recognized as causes of urinary tract infections in noncatheterized patients (Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae) were isolated in comparable frequencies by both the research and commercial laboratories. However, other organisms, including uncommon uropathogens like Providencia stuartii and Morganella morganii, which were actually among the most frequent bacteriuric species in these long-term-catheterized patients, were isolated significantly less frequently by the commercial laboratories. Reasons for the discrepancies are unclear but may involve use of different techniques. More complete reporting may lead to better understanding of the polymicrobial bacteriuria of long-term catheters and its associated complications. This, in turn, may result in improved patient care and infection control in nursing homes.

Monitoring breast cancer with CA 549.

CA 549, a new marker for breast cancer, was measured in serum of 719 patients by an immunoradiometric assay involving two monoclonal antibodies: BC4E 549, developed against a breast-tumor cell line, and BC4N 154, developed against milk fat-globule membrane. The reference interval for healthy women was 0-11 kilo-units/L. The percentages of patients with CA 549 greater than 11 kilo-units/L for benign conditions are: 0% pregnancy, 1% breast, 26% liver; and for nonbreast metastatic cancers: 12% endometrial, 33% lung, 40% prostatic, and 50% ovarian. In women with breast cancer who were receiving or had completed adjuvant therapy with no evidence of disease there was an 11% increase in CA 549. For patients with metastatic breast cancer, 19% of those in complete remission, 63% of those in partial remission, and 88% of those with systemic progression had increased CA 549. CA 549 is a more specific marker than carcinoembryonic antigen (CEA) in nonmalignant disease, nonbreast malignancies, and adjuvant breast-cancer patients, and it is more sensitive in breast-cancer patients with progressive disease than is CEA. We could show CA 549 to be superior to CEA for detecting active breast cancer in patients with malignant or nonmalignant breast diseases. In monitoring 19 adjuvant-treated patients, CA 549 correlated more closely with the clinical course than did CEA values and, when increased, predicted a clinical recurrence. In 18 breast-cancer patients with metastasis, monitored for two to three years, the change of CA 549 values paralleled disease courses more often than did CEA values.