The impact of obesity on receipt of adjuvant chemotherapy for breast cancer in the National Comprehensive Cancer Network (NCCN) centers.

Disparities in the receipt of adjuvant chemotherapy for early stage breast cancer is an important factor influencing mortality. We investigated whether greater body mass index (BMI) decreases receipt of adjuvant chemotherapy among women with operable breast cancer. In the NCCN breast cancer outcomes database, we identified women aged ≤ 70 with newly diagnosed stage I, II, or III breast cancer between 1997 and 2007, for whom use of adjuvant chemotherapy was classified as either standard-of-care or discretionary based on their clinical characteristics. Body mass index was assessed in categories (<18.5 kg/m(2) [underweight], 18.5 to <25 kg/m(2) [normal], 25 to <30 kg/m(2) [overweight], 30-39 kg/m(2) [obese], ≥ 40 kg/m(2) [extreme obese]). Multivariable logistic regression analysis was used to examine the association between BMI and receipt of chemotherapy in each classification group. 9,527 women were eligible for the study; 40% normal weight or less; 31% overweight; 24% obese; and 5% extremely obese. In multivariable analysis, there was no significant association between BMI and receipt of chemotherapy in either classification group. Among women for whom chemotherapy would be considered standard-of-care, older age (P < 0.001), comorbidity (P < 0.001), and non-Hispanic black ethnicity (P = 0.002) were associated with a lower likelihood of receipt of chemotherapy; however, the effect of ethnicity was not modified by obesity. Among women treated for operable breast cancer in the NCCN centers, BMI had no impact on receipt of adjuvant chemotherapy and did not modify the lower likelihood of chemotherapy among non-Hispanic black patients. Further investigation is needed into other factors that contribute to patient disparities in the receipt of chemotherapy in major academic centers.

Potential sources of Campylobacter infection on chicken farms: contamination and control of broiler-harvesting equipment, vehicles and personnel.

AIMS: To test the efficacy of enhanced biosecurity measures on poultry farms for reducing environmental contamination with Campylobacter during partial depopulation of broiler flocks prior to normal slaughter age. The study has also evaluated the risk of infection from live-bird transport crates that are routinely cleaned at the slaughterhouse, but may remain contaminated. METHODS AND RESULTS: On-farm sampling and Campylobacter isolation was undertaken to compare the prevalence of contamination on vehicles, equipment and catching personnel during farm visits that took place under normal or enhanced biosecurity. Campylobacters were found in almost all types of sample examined and enhanced biosecurity reduced the prevalence. However, the additional measures failed to prevent colonisation of the flocks. For transport crates, challenge trials involved exposure of broilers to commercially cleaned crates and genotyping of any campylobacters isolated. The birds were rapidly colonised with the same genotypes as those isolated from the cleaned crates. CONCLUSIONS: The enhanced biosecurity measures were insufficient to prevent flock colonisation, and the problem was exacerbated by inadequate cleaning of transport crates at the slaughterhouse. SIGNIFICANCE AND IMPACT OF THE STUDY: Current commercial practices in the United Kingdom facilitate the spread of campylobacters among broiler chicken flocks. Prevention of flock infection appears to require more stringent biosecurity than that studied here.

A chemoattractant receptor on macrophages exists in two affinity states regulated by guanine nucleotides.

The binding characteristics of the oligopeptide chemoattractant receptor on guinea pig macrophages and macrophage membrane preparations were characterized using detailed binding studies and computer analysis. Viable macrophages bound the radiolabeled chemoattractant N-formyl-methionyl-leucyl-[3H]phenylalanine with single dissociation constant (KD) of 18.4 +/- 4.6 nM with 15,300 +/- 1,800 sites per cell. Binding data from membrane preparations indicated the presence of two classes of binding sites with KD of 1.5 +/- 0.4 nM and 25.5 +/- 11.0 nM. Approximately 23% of the receptors were in the high affinity state. In the presence of added guanine nucleotide di- or triphosphates, the high affinity receptors in the membrane preparations were converted to low affinity states with no change in the total receptor number. Nonhydrolyzable derivatives of GTP were most potent in converting the receptor from its high to low affinity state. These data suggest that the affinity state of the oligopeptide chemoattractant receptor in macrophages is regulated by guanine nucleotides and GTPase, implying that the transduction mechanisms of this receptor may be controlled by a guanine nucleotide regulatory unit.

Sources and spread of thermophilic Campylobacter spp. during partial depopulation of broiler chicken flocks.

The practice of partial depopulation or thinning (early removal of a portion of birds from a commercial broiler flock) is a reported risk factor for Campylobacter colonization of residual birds because of the difficulty in maintaining biosecurity during the thinning process. The effect of this practice was studied in detail for 51 target flocks, each at a different growing farm belonging to one of seven major poultry companies throughout the United Kingdom. On 21 of these farms, the target flock was already colonized by Campylobacter, and at slaughter all cecal samples examined were positive, with a mean of 8 log CFU/g. An additional 27 flocks became positive within 2 to 6 days of the start of thinning and had similarly high levels of cecal carriage at slaughter. Just before the thinning process, Campylobacter was isolated frequently from the farm driveways, transport vehicles, equipment, and personnel. Strains from seven farms on which flocks became colonized after thinning were examined by pulsed-field gel electrophoresis typing. An association was found between strains occurring at specific sampling sites and those isolated subsequently from the thinned flocks. The results indicated that particular strains had spread from one farm to another when the farms were jointly owned by the same company and employed the same bird-catching teams and/or vehicles. These results highlight the need for better hygiene control in relation to catching equipment and personnel and more effective cleaning and disinfection of vehicles and bird-transport crates.

Probing the particulate microstructure of the aerodynamic particle size distribution of dry powder inhaler combination products.

The in-vitro aerosol performance of two combination dry powder inhaler (DPI) products, Foster® NEXThaler® and Seretide® Diskus® were investigated with single particle aerosol mass spectrometry (SPAMS). The in-vitro pharmaceutical performance is markedly different for both inhalers. Foster® NEXThaler® generates a higher fine particle fraction (FPF <5 µm) and a much higher relative extra fine particle fraction (eFPF <2 µm). In terms of the composition of the aerodynamic particle size distribution (APSD), it could be verified with SPAMS that overall Foster® NEXThaler® emits a significantly higher number of fine and extra fine particles with a median aerodynamic diameter (MAD) of 2.1 µm while Seretide® Diskus® had a larger MAD of 3.1 µm. Additionally, the interactions between the two active pharmaceutical ingredients (APIs) in both products are different. While Seretide® Diskus® emits a significant (37%) number of co-associated API particles, only a negligible number of co-associated API particles were found in Foster® NEXThaler® (<1%). A major difference with Foster® NEXThaler® is that it contains magnesium stearate (MgSt) as a second excipient besides lactose in a so-called 'dual excipient' platform. The data generated using SPAMS suggested that nearly all of the beclomethasone dipropionate particles in Foster® NEXThaler® also contain MgSt and must therefore be co-associated with this additional excipient. This may help explain why beclomethasone dipropionate in Foster® NEXThaler® forms less particle co-associations with the second API, formoterol fumarate, shows a lower cohesive strength in respect to beclomethasone itself and why both APIs exhibit superior detachment from the carrier as evidenced by the increased eFPF and smaller MAD.

Aldosterone and dexamethasone stimulate calcineurin activity through a transcription-independent mechanism involving steroid receptor-associated heat shock proteins.

Heat shock proteins (HSP) are components of the steroid receptor complex and are released into the cell cytosol after hormone binding. We tested whether HSPs released from steroid receptors mediate an increase in calcineurin phosphatase activity by steroid hormones. Aldosterone increased calcineurin activity in microdissected rat cortical collecting ducts (CCD) and connecting tubules, but not in proximal tubules, medullary thick ascending limb, or outer medullary collecting ducts. In contrast, 5 microM dexamethasone increased calcineurin activity in both CCD and proximal tubules. Aldosterone increased CCD calcineurin activity after 30 min and this response was blocked by spironolactone, but not by actinomycin D. An antibody recognizing HSP-56 did not change basal calcineurin activity, but completely blocked the stimulation of calcineurin by aldosterone. Rapamycin, an immunosuppressive drug that stabilizes the HSP-steroid receptor complex, also blocked the aldosterone response, whereas HSP-90 or HSP-70 increased calcineurin activity in permeabilized CCD. In summary, (a) aldosterone increases calcineurin activity in CCD through a transcription-independent process; (b) maneuvers inactivating HSP-56 or slowing HSP disassociation from the receptor complex blocks stimulation of calcineurin by steroid hormones; (c) HSP-90 and HSP-70 increase CCD calcineurin activity in the absence of steroid hormone. We conclude that HSPs released from transformed steroid receptors can stimulate calcineurin activity through a transcription-independent pathway.

Developing a risk-based trading scheme for cattle in England: farmer perspectives on managing trading risk for bovine tuberculosis.

This paper examines farmer attitudes towards the development of a voluntary risk-based trading scheme for cattle in England as a risk mitigation measure for bovine tuberculosis (bTB). The research reported here was commissioned to gather evidence on the type of scheme that would have a good chance of success in improving the information farmers receive about the bTB risk of cattle they buy. Telephone interviews were conducted with a stratified random sample of 203 cattle farmers in England, splitting the interviews equally between respondents in the high-risk area and low-risk area for bTB. Supplementary interviews and focus groups with farmers were also carried out across the risk areas. Results suggest a greater enthusiasm for a risk-based trading scheme in low-risk areas compared with high-risk areas and among members of breed societies and cattle health schemes. Third-party certification of herds by private vets or the Animal and Plant Health Agency were regarded as the most credible source, with farmer self-certification being favoured by sellers, but being regarded as least credible by buyers. Understanding farmers' attitudes towards voluntary risk-based trading is important to gauge likely uptake, understand preferences for information provision and to assist in monitoring, evaluating and refining the scheme once established.

Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects.

The profoundly elevated concentrations of low-density lipoproteins (LDL) present in homozygous familial hypercholesterolemia lead to symptomatic cardiovascular disease and death by early adulthood. Studies conducted in nonhepatic tissues demonstrated defective cellular recognition and metabolism of LDL in these patients. Since mammalian liver removes at least half of the LDL in the circulation, the metabolism of LDL by cultured hepatocytes isolated from familial hypercholesterolemic homozygotes was compared to hepatocytes from normal individuals. Fibroblast studies demonstrated that the familial hypercholesterolemic subjects studied were LDL receptor-negative (less than 1% normal receptor activity) and LDL receptor-defective (18% normal receptor activity). Cholesterol-depleted hepatocytes from normal subjects bound and internalized 125I-labeled LDL (Bmax = 2.2 micrograms LDL/mg cell protein). Preincubation of normal hepatocytes with 200 micrograms/ml LDL reduced binding and internalization by approx. 40%. In contrast, 125I-labeled LDL binding and internalization by receptor-negative familial hypercholesterolemic hepatocytes was unaffected by cholesterol loading and considerably lower than normal. This residual LDL uptake could not be ascribed to fluid phase endocytosis as determined by [14C]sucrose uptake. The residual LDL binding by familial hypercholesterolemia hepatocytes led to a small increase in hepatocyte cholesterol content which was relatively ineffective in reducing hepatocyte 3-hydroxy-3-methylglutaryl-CoA reductase activity. Receptor-defective familial hypercholesterolemia hepatocytes retained some degree of regulatable 125I-labeled LDL uptake, but LDL uptake did not lead to normal hepatocyte cholesterol content or 3-hydroxy-3-methylglutaryl-CoA reductase activity. These combined results indicate that the LDL receptor abnormality present in familial hypercholesterolemia fibroblasts reflects deranged hepatocyte LDL recognition and metabolism. In addition, a low-affinity, nonsaturable uptake process for LDL is present in human liver which does not efficiently modulate hepatocyte cholesterol content or synthesis.

Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials. POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. OUTCOMES: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. VALUES: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A "recommendation" was made when level I or II evidence was available and there was consensus as to its meaning. A "suggestion" was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS: The recommendations, suggestions, and expert opinions of the Panel are described in this article. VALIDATION: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.

Pathologic findings in nonpalpable invasive breast cancer.

Previous studies have shown that patients with nonpalpable invasive breast cancer have a favorable prognosis. These studies, however, have not analyzed pathologic features of mammographically detected tumors according to tumor size. We describe the histopathologic features of 77 nonpalpable invasive breast cancers, comparing neoplasms less than or equal to 1 cm with larger clinically occult tumors. Forty-seven lesions (61%) were less than or equal to 1 cm (group A) and 30 (39%) were greater than 1 cm (group B). In group A, there were 30 infiltrating ductal carcinomas (IDC); seven infiltrating lobular carcinomas (ILC); and two cases each of mixed ILC and IDC, mixed tubular carcinoma and ILC, and infiltrating cribriform carcinoma. There was one case each of mucinous carcinoma, apocrine carcinoma, tubular carcinoma, and mixed mucinous and IDC. In group B, there were 23 (77%) IDC, five (17%) ILC, and two mixed IDC and ILC. Tumors in group B were more frequently grade 3 (22% versus 7%), but this was not statistically significant (p = 0.21). There were no important differences in the frequency, subtypes and location of carcinoma in situ, or other histopathologic parameters evaluated in the biopsy specimens. Mastectomy specimens with axillary lymph node dissections were available for review in 64 cases (83%). Group B patients had a higher rate of residual invasive carcinoma (31% versus 13%) and lymph node metastases (31% versus 16%), but these differences were not statistically significant. Residual carcinoma in situ was more frequent in group B (54%) compared with group A (26%) (p = .036). Of seven group B cases with negative biopsy margins, residual invasive carcinoma was present in five (71%). We conclude that small nonpalpable invasive breast cancers differ from larger nonpalpable tumors primarily in size. The finding of negative biopsy margins should not be construed as conclusive evidence for the absence of residual infiltrating disease.

Apolipoprotein B synthesis in humans: liver synthesizes only apolipoprotein B-100.

Apolipoprotein (apo) B-100 and B-48 are prominent apolipoproteins in VLDL, IDL, and chylomicrons. Organ cultures of normal adult human liver were established to ascertain the form of apo B synthesized by hepatocytes in humans. Human liver was minced and incubated in 15 mL methionine-free RPMI-1640 medium with 10% dialyzed fetal calf serum plus 250 microCi 35S-methionine for eight hours at 37 degrees C. Lipoproteins secreted by the liver were isolated by ultracentrifugation and the content of newly synthesized apo B determined by quantitation of radioactivity in the apoB-100 and apoB-48 bands after separation by 3% NaDodSO4 gel electrophoresis. In the eight-hour period, 2.5% to 3.2% of added 35S-methionine was secreted in TCA-precipitable protein of which 0.34% was apo B. Ninety-nine percent of the apo B in VLDL, IDL, and LDL was in the apo B-100 electrophoretic band. No significant radioactivity was detected in the apo B-48 electrophoretic band. Eighty-nine percent of the total radioactivity of apo B-100 was in VLDL with 3% and 8% in IDL and LDL, respectively. These results establish that adult human liver in organ culture synthesizes apo B-100 but not apo B-48.

Paget's disease of the breast: a 33-year experience.

BACKGROUND: Paget's disease (PD) of the breast is an uncommon condition traditionally treated with mastectomy. To assess the natural history and treatment options in PD we have reviewed the experience at the Roswell Park Cancer Institute (RPCI). STUDY DESIGN: The medical records of patients treated for PD at RPCI between 1963 and 1996 were reviewed. RESULTS: Eighty patients were treated in the period reviewed. The median follow up was 61 months. Sixty-eight of 80 patients had nipple changes consistent with PD including 30 who had an associated breast mass (group 1), and 38 who had no associated mass (group 2). Of the 68 patients with clinical PD, 58 (85%) were treated with mastectomy while the remainder were treated with some form of breast conserving therapy. Breast cancer (BC) was found in 56 of 68 patients (82%) with clinical PD, including 28 of 30 patients (93%) in group 1 and 28 of 38 patients (74%) in group 2. Breast cancer was centrally located (within 2 cm of the areolar margin) in 61% of patients, including 71% in group 1 and 50% in group 2. Of the 28 patients with an associated BC in group 1, 21 (75%) had invasive cancer, 6 (21%) had ductal carcinoma in situ (DCIS), and 16 (57%) had pathologic axillary nodes. Of the 28 patients with an associated BC in group 2, 10 (36%) had invasive cancer, 18 (64%) had DCIS, and 6 (21%) had positive axillary nodes. The median survival was significantly shorter for group 1 (42 months) than for group 2 (126 months; p = 0.007). CONCLUSION: Most patients with PD have an associated BC (82%) that was centrally located (61%). In those patients without an associated mass, a significant number (26% in this series) may not have an underlying BC and may be overtreated with mastectomy. On the other hand, a significant number of patients with PD and no associated breast mass will be found to have a peripherally located tumor (29% in this series). These non-central BC masses could potentially be missed by a wide local excision that includes the areolar complex.

The evaluation of palpable breast masses: common pitfalls and management guidelines.

The management of a palpable breast mass starts with identification of the lesion and a suspicion of malignancy. While seemingly simple, the initial evaluation can significantly impact upon treatment options and outcomes. The management of two patients recently referred to this Institution highlights common pitfalls and technical considerations in the diagnosis and treatment of palpable breast masses. The case histories of two patients referred after open breast biopsy were examined. The English language medical literature was searched manually and by Medline for publications related to the evaluation of palpable breast masses. Imaging, diagnostic techniques and technical considerations in the management of palpable lesions were reviewed. The initial use of carefully selected diagnostic and therapeutic measures is critical in optimizing outcomes measured in improved quality of life and survival. Inappropriate choices at this first stage can have extremely negative consequences. The early evaluation of two patients highlighted these considerations. Management pitfalls included serial examination of a suspicious lesion, failure to obtain a mammogram prior to excisional biopsy and unnecessary testing. Technical problems included piecemeal excision of the tumor with positive margins, use of a drain, closure of deep tissues with dimpling of the breast, and incision placement in a location that subsequently necessitated mastectomy. Careful adherence to the clinical and operative principles of breast cancer management optimizes outcomes in the evaluation of palpable breast masses.

Incorporation of laparoscopy into a surgical endoscopy training program.

The impact of introducing laparoscopy as part of the overall gastrointestinal endoscopy case load performed by residents was reviewed. During 1990, there was a significant increase (56.9%) in the number of flexible diagnostic endoscopic procedures performed compared with 1989. When the total number of laparoscopic procedures was considered, the increase was 117%. Residents participated in the "surgeon's" position in 59% of the therapeutic laparoscopic procedures and as either surgeon or "first assistant" in 86% of all therapeutic laparoscopic procedures and 94% of all diagnostic laparoscopic procedures. Complication rates for diagnostic laparoscopic procedures were low in 1989 (0.03%) and 1990 (0.2%). Complication rates for therapeutic laparoscopic procedures were also low (4%). There was no difference in the complication rate for cases in which residents were in the surgeon's position (4%) versus cases in which they were not (4%). Introduction of laparoscopic procedures into a surgical residency program can be done safely, especially in cases in which an established program in endoscopy exists.

Laparoscopic versus traditional appendectomy for suspected appendicitis.

We compared the results of concurrently performed laparoscopic versus open appendectomy as treatments for suspected acute appendicitis. The 68 laparoscopic procedures resulted in 62 appendectomies, 47 by the laparoscopic (LA) technique and 15 by the open (LO) technique. Another 54 patients underwent open appendectomy (OA). Significantly more females underwent laparoscopy (LA and LO: 52% versus OA: 33%, p = 0.047). Operative duration was shortest for OA (81 +/- 3 minutes), which was shorter than for LO (108 +/- 7 minutes), but not different than LA (86 +/- 6 minutes). The postoperative length of stay was not different for LA (3.5 +/- 0.5 days) compared with OA (5.9 +/- 1.6 days) or LO (4.8 +/- 1.3 days). One death occurred in the OA group. Wound complication rates were not significantly different for LA (4.3%) compared with OA (9.4%) and LO (13.3%). Overall complication rates were lower for LA (10.6%) and OA (18.9%) compared with LO (46.7%, p < 0.01). Median hospital cost for LO ($10,425) was higher (p < 0.02) than for either LA ($5,899) or OA ($5,220). When appendicitis was not present, definitive confirmation of pathology was achieved in 9 of 18 patients undergoing LA versus 4 of 14 patients having OA (p = not significant). We conclude that when laparoscopy and laparoscopic appendectomy can be performed, the procedure is safe and produces results comparable with those of open appendectomy without significant overall cost differences.

Breast cancer practice guidelines: evaluation and quality improvement.

The utility of practice guidelines in breast cancer management remains unproved. This paper examines the scope and goals of published guidelines and their utility in the process of breast cancer treatment quality improvement. Although existing breast cancer guidelines vary widely in scope and intent, they provide a framework for meaningful quality-of-care evaluation. Among the few comprehensive breast cancer guideline programs are those developed by the Ontario Cancer Treatment Practice Guidelines Initiative, the Revlon/UCLA Breast Center, the Association of Community Cancer Centers (ACCC), the Society of Surgical Oncology (SSO), and the National Comprehensive Cancer Network (NCCN). Ultimately, guidelines will prove useful only if they are utilized as part of a comprehensive program to improve quality, cost-effectiveness, and outcomes. To accomplish this, they must include mechanisms for revision and evaluation. The evaluation of guideline utility in quality improvement, particularly in breast cancer care, is a complex long-term process, which should include input from practitioners, institutions, payors, and government.

NCCN Practice Guidelines for Breast Cancer.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. In many situations, the patient and physician have the responsibility to jointly explore and ultimately select the most appropriate option from among the available alternatives. With rare exception, the evaluation, treatment, and follow-up recommendations contained within these guidelines were based largely on the results of past and present clinical trials. However, there is not a single clinical situation in which the treatment of breast cancer has been optimized with respect to either maximizing cure or minimizing toxicity and disfigurement. Therefore, patient and physician participation in prospective clinical trials allows patients not only to receive state-of-the-art cancer treatment but also to contribute to the improvement of treatment of future patients.

In-situ ablation of breast cancer.

Recent trends in the management of early breast cancer have moved toward breast conservation, without a loss in disease-free intervals or overall survival. The in situ ablation of breast tumors without the need for lumpectomy is the next logical extension of this trend. Advances in stereotactic guided localization, ultrasound and magnetic resonance imaging (MRI) technology has markedly improved our ability to visualize, biopsy and possibly treat breast tumors. With these technologies, probes for delivery of energy for ablating tumors and for monitoring the effect can be placed precisely within breast tumors. Several methods are available to destroy tumors in situ, based on thermal destruction of tumor with either heat or cold. Cryoablation is performed using a liquid-nitrogen cooled needle. Heating techniques include delivery of the heat through probes placed in the lesion to conduct radiofrequency irradiation or laser light energy. Two techniques, focused ultrasound and focused microwave thermotherapy, are truly non-invasive in that they do not involve any skin puncture. In addition to the incentive of eliminating lumpectomy from the treatment paradigm for early stage breast cancer, and the potential cosmetic advantages, in situ ablation may also provide an immunological benefit by providing a source of antigens for the development of a systemic anti-tumor immune response. The augmentation of this response may provide an advantage to in situ ablation in terms of recurrence and survival rates.

Breast cancer imaging.

The role of the surgeon in the diagnosis and management of breast cancer continues to evolve as office based diagnostic procedures gain more prominence. This article outlines the basic clinical and technical aspects of mammography and ultrasound. The evaluation and management of several challenging breast problems are discussed.

High-dose oral and intravenous metoclopramide in doxorubicin/cyclophosphamide-induced emesis. A randomized double-blind study.

Emesis remains a major side effect of cancer chemotherapy. High-dose intravenous metoclopramide has proved to be effective antiemetic therapy for cisplatinum induced emesis. It has not been rigorously tested in nonplatinum chemotherapy. This double-blind, noncrossover, randomized trial compared high-dose oral and intravenous metoclopramide to standard oral prochlorperazine in emesis caused by doxorubicin [70 mg/m2 body surface area (BSA)] and cyclophosphamide (700 mg/m2 BSA). Prochlorperazine (10 mg/dose), oral metoclopramide, and intravenous metoclopramide (2 mg/kg/dose each) were given 30 min before chemotherapy and then every 4 h for 24 h. Ten patients were randomized to prochlorperazine therapy, 10 to oral metoclopramide, and 9 to i.v. metoclopramide. Median number of emeses for the first chemotherapy cycle was 3, 3, and 7 for prochlorperazine, oral, and i.v. metoclopramide, respectively. Statistical analysis showed no significant advantage of any regimen (p greater than 0.4). For patients who continued the antiemetic study, frequency of emesis increased with each successive cycle of chemotherapy. Six of 19 patients treated with metoclopramide developed dystonic reactions compared with zero of 10 on prochlorperazine. High plasma metoclopramide levels were achieved with both metoclopramide regimens and did not correlate with frequency of emesis. High-dose oral and i.v. metoclopramide in an every 4 h regimen did not show any advantage over standard antiemetic therapy for doxorubicin/cyclophosphamide-induced emesis and were associated with significant toxicity.