Impact of prior systemic therapy on lymphocytic infiltration in surgically resected breast cancer brain metastases.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) have been positively correlated with response to systemic therapy for triple-negative and HER2 + subtypes and improved clinical outcomes in early breast cancer (BC). Less is known about TILs in metastatic sites, particularly brain metastases (BM), where unique immune regulation governs stromal composition. Reactive glial cells actively participate in cytokine-mediated T cell stimulation. The impact of prior medical therapy (chemotherapy, endocrine, and HER2-targeted therapy) on the presence of TILs and gliosis in human breast cancer brain metastases (BCBM) has not been previously reported. METHODS: We examined prior treatment data for 133 patients who underwent craniotomy for resection of BMs from the electronic medical record. The primary endpoint was overall survival (OS) from the time of BM diagnosis. We examined the relationship between prior systemic therapy exposure and the histologic features of gliosis, necrosis, hemorrhage, and lymphocyte infiltration (LI) in BCBMs resected at subsequent craniotomy in univariate analyses. RESULTS: Complete treatment data were available for 123 patients. BCBM LI was identified in 35 of 116 (30%) patients who had received prior systemic treatment versus 5 of 7 (71.4%) who had not {significant by Fisher's exact test p = 0.045}. There were no statistically significant relationships between prior systemic therapy and the three other histologic variables examined. CONCLUSIONS: This observation suggests that systemic therapy may interfere with the immune response to BCBMs and cause exhaustion of anti-tumor immunity. This motivates clinical investigation of strategies to enhance LI for therapeutic benefit to improve outcomes for patients with BCBMs.

Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia.

OBJECTIVE: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. METHODS: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval (CI) = -0.57 to -0.17, P < 0.001], driven by negative (SMD = -0.25, 95% CI = -0.44-0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = -0.42, 95% CI = -0.77, -0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = -0.71, 95% CI = -1.21, -0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = -0.43, 95% CI = -0.77, -0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04-2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation. CONCLUSIONS: For schizophrenia patients on stable antipsychotic treatment, adjunctive antidepressants are effective for total and particularly negative symptom reduction. However, effects are small-to-medium, differ across antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.

Paclitaxel efficacy and toxicity in older women with metastatic breast cancer: combined analysis of CALGB 9342 and 9840.

BACKGROUND: Two Cancer and Leukemia Group B (CALGB) studies were utilized to determine the efficacy and tolerability of paclitaxel (Taxol) in older patients with metastatic breast cancer. PATIENTS AND METHODS: CALGB 9840 evaluated weekly paclitaxel (80 mg/m(2)) versus paclitaxel every 3 weeks (175 mg/m(2)); CALGB 9342 evaluated three doses of paclitaxel as follows: 175, 210 and 250 mg/m(2) each over 3 h every 3 weeks. Of the 1048 patients, paclitaxel was used first line in 57%. The groups: (i) <55 years (45%), (ii) 55-64 years (29%), and (iii) ≥65 years (26%). RESULTS: Tumor response was also similar among age groups. First-line therapy (P = 0.0001) and better performance status (PS) (P = 0.018) were significantly related to higher response. Age did not significantly relate to overall survival (OS) or progression-free survival (PFS). First-line therapy, better PS, estrogen receptor positive status and a fewer number of metastatic sites were significantly related to improved OS and PFS. The grade ≥3 toxic effects that increased linearly with age were leucopenia (P = 0.0099), granulocytopenia (P = 0.022), anorexia (P = 0.028), bilirubin elevation (P = 0.0035) and neurotoxicity (P < 0.0001). Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity. CONCLUSIONS: Older women with breast cancer derive similar efficacy from treatment with paclitaxel as younger women. Older women are at increased risk for specific toxic effects.

A phase II pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group.

BACKGROUND: E2104 was designed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive randomized phase III trial. PATIENTS AND METHODS: Patients were sequentially assigned to one of two treatment arms. In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) (ddAC→T), all patients received bevacizumab (10 mg/kg every 2 weeks × 26) initiated either concurrently with AC (Arm A: ddBAC→BT→B) or with paclitaxel (Arm B: ddAC→BT→B). The primary end point was incidence of clinically apparent cardiac dysfunction (CHF). RESULTS: Patients enrolled were 226 in number (Arm A 104, Arm B 122). Grade 3 hypertension, thrombosis, proteinuria and hemorrhage were reported for 12, 2, 2 and <1% of patients, respectively. Two patients developed grade 3 or more cerebrovascular ischemia. Three patients in each arm developed CHF. There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of >15% or >10% to below the lower limit of normal post AC or post bevacizumab. CONCLUSIONS: Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity. The definitive phase III trial (E5103) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function.

A phase I study of dasatinib and weekly paclitaxel for metastatic breast cancer.

BACKGROUND: SRC plays an important role in the pathogenesis of metastatic breast cancer (MBC). In preclinical models, paclitaxel and the oral SRC inhibitor dasatinib showed greater antitumor activity than either agent. To determine the maximum tolerated dose of this combination, we conducted a phase I study. PATIENTS AND METHODS: Patients with MBC; Eastern Cooperative Oncology Group performance status of zero to one; normal hepatic, renal and marrow function were eligible. Paclitaxel 80 mg/m(2) was given 3 weeks of 4. The starting dasatinib dose was 70 mg and was increased, using a standard 3 + 3 dose-escalation scheme. RESULTS: Fifteen patients enrolled (median age 54 years, range 35-74). No dose-limiting toxic effects (DLTs) occurred at dasatinib doses of 70-120 mg. One DLT (grade 3 fatigue) occurred in the dasatinib 150-mg cohort, which was expanded (six patients) with no further DLTs. However, due to cumulative toxic effects (rash, fatigue, diarrhea), the recommended phase II dose is dasatinib 120 mg. Of 13 assessable patients, a partial response was seen in 4 patients (31%), including 2 patients previously treated with taxanes; all received ≥120 mg dasatinib. An additional five patients (29%) had stable disease. CONCLUSION: In combination with weekly paclitaxel, the recommended phase II dose of dasatinib is 120 mg daily and preliminary activity has been seen in patients with MBC.

Breast carcinoma with brain metastases: clinical analysis and immunoprofile on tissue microarrays.

BACKGROUND: Development of brain metastasis in patients with breast carcinoma correlates with poor outcome. Identification of tumor characteristics associated with breast cancer brain metastases (BCBM) could help identify patients at risk. PATIENTS AND METHODS: We studied 209 patients with BCBM. We evaluated a panel of proteins relevant to the biology of breast carcinoma on tissue microarrays of 133 primary tumors and 56 BCBM, including paired samples from 43 patients, and correlated the findings with the clinical outcome. RESULTS: The median survival after BCBM diagnosis was 19 months (95% confidence interval, 13-23 months). Patients presenting with solitary metastasis had a significantly longer median survival than those with multiple lesions (25 versus 11 months, P ≤ 0.0001). We found no significant discordance in the expression of tested markers, but identified a possible association between the expression of basal cytokeratin CK5/6 in the primary carcinoma and the development of multiple rather than solitary brain metastases. CONCLUSIONS: Expression of antigens commonly associated with breast carcinoma does not differ significantly between the primary tumor and the corresponding brain metastases. Although no specific immunoprofile identifies breast carcinomas that develop brain metastases, we observed a possible association between CK5/6 expression in the primary tumor and multiple versus solitary BCBM.

Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer.

BACKGROUND: Safety and efficacy of gemcitabine plus docetaxel (GD) and capecitabine plus docetaxel (CD) were compared in patients with metastatic breast cancer, where the alternate crossover monotherapy (GD→C or CD→G) was predetermined. PATIENTS AND METHODS: Patients were randomly assigned to 3-week cycles of either gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 75 mg/m(2) on day 1 or capecitabine 1000 mg/m(2) twice daily on days 1-14 plus docetaxel 75 mg/m(2) day 1. Upon progression, patients received crossover monotherapy. Primary end point was time to progression (TtP). Secondary end points evaluated overall response rate (ORR), overall survival (OS), and adverse events (AEs). RESULTS: Despite over-accrual of 475 patients, the trial matured with only 324 of 385 planned TtP events due to patient discontinuations. Human epidermal growth factor receptor 2 status was not captured in this study. More CD patients (28%) discontinued due to AEs than GD patients (18.0%, P = 0.009). TtP [hazard ratio (HR) = 1.101, 95% confidence interval (CI) 0.885-1.370, P = 0.387] and OS (HR = 1.031, 95% CI 0.830-1.280, P = 0.785) were not significantly different comparing GD and CD. ORR was not statistically different (P = 0.239) comparing GD (72 of 207, 34.8%) and CD (78 of 191, 40.8%). TtP, OS, and ORR were not significantly different comparing crossover groups. GD caused greater fatigue, hepatotoxicity, neutropenia, and thrombocytopenia but not febrile neutropenia; CD caused more hand-foot syndrome, gastrointestinal toxicity, and mucositis. CONCLUSIONS: GD and CD produced similar efficacy and toxicity profiles consistent with prior clinical experience.

Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate.

PURPOSE: We explored the relationship between circulating HER2 extracellular domain (ECD) and tissue HER2 status as determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). We also examined its predictive value in a cohort of metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel. METHODS: Eligible patients had pre- and post-treatment stored serum specimens and were treated on a previously reported phase II trial. Retrospective analysis evaluated: the association between pretreatment serum HER2 ECD and tissue HER2 status by IHC and FISH; and the association between change in serum HER2 ECD after 12 weeks of therapy and response proportion. RESULTS: Stored serum samples were available for 55/95 (58%) patients. Statistically significant associations were found between HER2 status as assessed by IHC and FISH, and baseline serum HER2 ECD level. Patients whose ECD normalized after 12 weeks of therapy had a higher response proportion compared with patients with persistently high ECD levels (68% versus 15%, P=0.005). A relative decline of over 55% from baseline HER2 ECD predicted response to therapy. CONCLUSION: A statistically significant association was observed between pretreatment serum HER2 ECD and tissue HER2 status as assessed by IHC and FISH. A decrease in serum HER2 ECD level was a significant predictor of response to trastuzumab-based therapy.

Doxorubicin followed by sequential paclitaxel and cyclophosphamide versus concurrent paclitaxel and cyclophosphamide: 5-year results of a phase II randomized trial of adjuvant dose-dense chemotherapy for women with node-positive breast carcinoma.

PURPOSE: We conducted a randomized Phase II trial to directly compare toxicity, feasibility, and delivered dose intensities of two adjuvant dose-intensive regimens containing doxorubicin, paclitaxel, and cyclophosphamide for patients with node-positive breast carcinoma. EXPERIMENTAL DESIGN: Forty-two patients with resected breast carcinoma involving one or more ipsilateral axillary lymph nodes, were randomized to receive two different schedules of adjuvant chemotherapy using 14-day dosing intervals: either (a) three cycles of doxorubicin 80 mg/m(2) as i.v. bolus followed sequentially by three cycles of paclitaxel 200 mg/m(2) as a 24-h infusion and then by three cycles of cyclophosphamide 3.0 g/m(2) as a 1-h infusion (arm A); or (b) the same schedule of doxorubicin followed by three cycles of concurrent cyclophosphamide and paclitaxel at the same doses (arm B). All cycles were supported by granulocyte colony-stimulating factor administration. RESULTS: Forty-one patients were assessable for toxicity and feasibility; 37 (90%) completed all planned chemotherapy. There was no treatment-related mortality; however, increased toxicity was observed on arm B compared with arm A, manifested by an increase in hospitalization for toxicity, mainly neutropenic fever, and an increased incidence of transfusion of packed RBCs transfusions for anemia. The mean delivered dose intensities for paclitaxel and cyclophosphamide were significantly greater for arm A compared with arm B (P =.01 and P =.05, respectively). There is no long-term, treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSIONS: Dose-dense sequential single-agent chemotherapy is more feasible than doxorubicin with subsequent concurrent paclitaxel and cyclophosphamide.

Oral gossypol in the treatment of patients with refractory metastatic breast cancer: a phase I/II clinical trial.

Gossypol has demonstrated in vitro effects on cell cycle regulation and anti-tumor activity against mammary carcinoma cell lines. This Phase I/II study assesses both the effect of gossypol on cell cycle regulatory proteins in vivo and the clinical effect. Twenty women with refractory metastatic breast cancer received oral gossypol at daily doses between 30 and 50 mg per day. Gossypol plasma levels were measured (n = 8) and the modulation of the retinoblastoma (Rb) gene protein and Cyclin D1 was assessed by serial biopsies (n = 4). Grade I-II toxicities with gossypol treatment included nausea in 30% of patients, fatigue 15%, emesis 15%, altered taste sensation 15% and diarrhea in 10% of patients. Two of the three patients receiving 50 mg/day experienced dose limiting dermatologic toxicity (grade III). One patient had a minor response and two patients had stable disease with > 50% decline in serial assessments of the serum tumor markers. Immunohistochemical analysis of cyclin D1 and Rb expression in serial biopsies of four patients revealed both a concurrent decrease in cyclin D1 expression and an increase in nuclear Rb expression in three patients. The maximal tolerated dose (MTD) of gossypol was 40 mg/day. Gossypol appears to affect the expression of Rb protein and cyclin D1 in breast cancer metastases at doses achievable, yet had negligible antitumor activity against anthracycline and taxane refractory metastatic breast cancer. The cell cycle regulatory effects of gossypol suggest a potential role for gossypol as a modulating agent in conjunction with other cell cycle specific compounds.

Pharmacologic insights into the future of trastuzumab.

A combination of factors has been responsible for improvements in cancer survival and cure rates. In addition to new therapies with novel/genetic targets, these include improvements in drug delivery, new schedules/sequencing of drug administration and the identification of combination therapies with greater activity/dose density than existing regimens. The recognition that such criteria can affect treatment outcome has led to their incorporation into clinical trials of new drugs. Furthermore, pharmacokinetic and pharmacodynamic parameters have become increasingly important for the rational selection of dose, administration route and schedule. The humanized monoclonal antibody trastuzumab (Herceptin) has been rationally developed to target the human epidermal growth factor receptor-2 (HER2), which is overexpressed in 20%-30% of breast cancers and is associated with poor prognosis. Trastuzumab when administered i.v. on a weekly schedule either alone or in combination with taxanes, improves survival of women with HER2-positive metastatic breast cancer. Based upon pharmacokinetic considerations, current studies are examining whether trastuzumab can be administered i.v. every three weeks or by the s.c. route. These regimens would have advantages for patients and medical staff in terms of acceptability, ease of administration and, potentially, cost effectiveness. Furthermore, various combinations of trastuzumab and chemotherapeutic agents are being explored with the aim of identifying the optimal combination regimen for clinical use. The rationale for these various studies and the studies themselves are described.

The evolving role of gemcitabine in the management of breast cancer.

Despite the common clinical use of numerous active cytotoxic agents for breast cancer therapy, and the combinations that are derived from them, the median survival for patients with metastatic breast cancer has not been dramatically improved over the past two decades. Furthermore, when the expected outcome of treatment is not cure, optimizing the dynamic equilibrium between chemotherapy-induced side effects and the benefits attributable to chemotherapy-mediated relief of cancer-related symptomatology becomes paramount. The search for active agents to this end has recently included the clinical evaluation of the novel nucleoside analogue gemcitabine (2',2'-difluorodeoxycytidine). This review summarizes the recent and current development of this agent.

Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification.

PURPOSE: This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridization (FISH) assay results. PATIENTS AND METHODS: Eligible patients had bidimensionally measurable metastatic breast cancer. Up to three prior chemotherapy regimens, including prior anthracycline and taxane therapy, were allowed. Trastuzumab 4 mg/kg and paclitaxel 90 mg/m2 were administered on week 1, with trastuzumab 2 mg/kg and paclitaxel 90 mg/m2 administered on subsequent weeks. HER2 status was evaluated using four different immunohistochemical assays and FISH. RESULTS: Patients received a median of 25 weekly infusions (range, one to 85 infusions). Median delivered paclitaxel dose-intensity was 82 mg/m2/wk (range, 52 to 90 mg/m2/wk). The intent-to-treat response rate for all 95 patients enrolled was 56.8% (95% confidence interval, 47% to 67%). A response rate of 61.4% (4.5% complete response, 56.8% partial response) was observed in 88 fully assessable patients. In patients with HER2-overexpressing tumors, overall response rates ranged from 67% to 81% compared with 41% to 46% in patients with HER2-normal expression (ranges reflect the different assay methods used to assess HER2 status). Differences in response rates between patients with HER2-overexpressing tumors and those with normal HER2 expression were statistically significant for all assay methods, with CB11 and TAB250 antibodies and FISH having the strongest significance. Therapy was generally well tolerated, although three patients had serious cardiac complications. CONCLUSION: Weekly trastuzumab and paclitaxel therapy is active in women with metastatic breast cancer. Therapy was relatively well tolerated; however, attention to cardiac function is necessary.

Phase I study of a third-generation selective estrogen receptor modulator, LY353381.HCL, in metastatic breast cancer.

PURPOSE: We conducted this phase I trial to determine the safety and toxicity profile of LY353381.HCl-a novel, potent, third-generation selective estrogen receptor modulator (SERM)-because this benzothiophene derivative demonstrated an SERM profile in preclinical studies. PATIENTS AND METHODS: We studied 32 patients with recurrent or metastatic breast cancer. Patients were treated in four cohorts with oral daily doses of 10, 20, 50, and 100 mg. Pharmacokinetic sampling was performed during the first 72 hours following the first dose on day 1 and during the 24 hours after the day 57 dose. Eligibility criteria included Eastern Cooperative Oncology Group performance status of 0 to 2; no significant major organ dysfunction; and at least 3 weeks elapsed since most recent hormonal therapy, chemotherapy, and estrogen replacement therapy. RESULTS: The median patient age was 56 years (range, 30 years to 76 years). The median number of prior chemotherapies for metastatic disease was one (range, zero to four), while the median number of prior hormone regimens for metastatic disease was two (range, zero to five). Receptor status was estrogen receptor (ER) positive and progesterone receptor (PR) positive, 19 patients; ER positive and PR negative, eight patients; ER positive and PR unknown, two patients; and ER and PR unknown, three patients. Dose-limiting toxicity was not observed. Treatment was well tolerated with mild to moderate hot flashes in 18 of 32 patients (56%) at all dose levels. Transvaginal ultrasound performed at baseline and after 12 weeks of treatment showed no endometrial thickening. Of the 32 patients evaluable for response, six patients had stable disease for at least 6 months with a median duration of 7.7 months (range, 6.2 months to 33.8 months). The pharmacokinetics of LY353381.HCl were generally linear with respect to time and studied dose range. CONCLUSION: As predicted in preclinical testing, daily oral LY353381.HCl is safe, is well tolerated at all tested dose levels, and may be clinically beneficial in patients with extensively pretreated metastatic breast cancer. Further studies with LY353381 to evaluate the efficacy in patients with or without prior exposure to tamoxifen and fewer overall prior regimens are under way.

Gemcitabine as single-agent therapy in the management of advanced breast cancer.

Many active cytotoxic agents exist for breast cancer therapy, and numerous combination chemotherapy regimens are derived from them. Creating these combinations is sometimes empirically motivated by non-overlapping toxicities or the expectation of non-cross resistance. Yet, there is usually no absolute division of these aspects among cytotoxic agents, and the median survival for patients with metastatic breast cancer has not been dramatically prolonged by this approach. When the outcome of treatment is palliation rather than cure, it becomes paramount to optimize the dynamic equilibrium between chemotherapy-induced side effects and the benefits attributable to relief of cancer-related symptoms. To this end, several recent clinical trials have evaluated the novel nucleoside analog gemcitabine (Gemzar) as single-agent therapy for advanced breast cancer. This article reviews these trials.

Sexual dysfunction and depression: etiology, prevalence, and treatment.

Sexual dysfunction and depression are very common conditions that are age-related and chronic. In men, epidemiologic studies have confirmed a strong correlation between erectile dysfunction and symptoms of depression. Both conditions have a significant negative impact on the quality of life of patients and their partners. Several studies showed that restoration of normal sexual function improves the quality of life of patients and their partners, regardless of treatment method. The literature review and recent observations emphasize the multifactorial nature of sexual dysfunction and, more specifically, erectile dysfunction and underline the importance of the comorbidity and bidirectional relationship between erectile dysfunction and depression. Research is progressing on the possible link between andropause, sexual dysfunction, and depression, thus opening potential new opportunities to address issues of aging-related morbidities.

An immunotherapeutic approach to treatment of breast cancer: focus on trastuzumab plus paclitaxel. Breast Cancer Medicine Service.

Recent emphasis has focused on the development of an immunotherapeutic approach toward the treatment of breast cancer. In particular, evaluation of antibodies and vaccines are active areas of research. The monoclonal antibody trastuzumab (H), directed against the HER-2/neu protein, has resulted in inhibition of tumor growth in both preclinical and clinical studies. This effect can be increased when used in combination with several chemotherapeutic agents. A randomized trial of chemotherapy alone versus chemotherapy plus H in untreated metastatic breast cancer patients found prolonged survival in the combination therapy arm. Cardiac toxicity was increased with doxorubicin and cyclophosphamide plus H but not for paclitaxel (T) plus H. Several trials of dose-dense weekly T have found minimal toxicity and significant clinical benefit. These findings prompted the initiation of a trial to evaluate weekly 1-h T plus weekly H. Preliminary data from this ongoing study demonstrate few side effects and a response rate of 64% (95%CI 42-76%). The optimal role of H in the treatment of breast cancer has not yet been defined. Additional evaluation in the metastatic and adjuvant settings is planned.

High prevalence of alcoholism in dialysis patients.

Alcoholism is one of the most common psychosocial disorders, affecting approximately 10% of the general population. The impact of alcoholism on the care of patients with other medical illnesses has not been addressed in many of these populations, including patients with end-stage renal disease (ESRD) undergoing hemodialysis. We set out to determine the prevalence of alcoholism in an urban hemodialysis population and ascertain whether alcoholism had an effect on compliance in this population. One hundred sixty-three urban hemodialysis patients were screened using the Michigan Alcoholism Screening Test (MAST), a 25-item questionnaire that has been validated in multiple trials. Forty-five patients (27.6%) scored 5 or greater on the MAST. The MAST-positive subjects were younger (age, 55 +/- 15 years versus 64 +/- 13 years) and tended to be men (58% versus 43%). There was no significant difference in the incidence of diabetic kidney disease; however, there were significantly more human immunodeficiency virus (HIV)-positive patients in the MAST-positive group. The dietary compliance measures of predialysis potassium or phosphorus levels did not differ between the two groups. A trend toward lower serum albumin level was evident in the men in the MAST-positive group (3.75 +/- 0.57 versus 3.91 +/- 0.30 g/dL; P = 0.0212). In conclusion, there is a high prevalence of alcoholism in the urban dialysis population. Alcoholic patients with ESRD are younger and tend to be men. HIV-positive patients with ESRD have a high prevalence of concomitant alcoholism. Compliance indicators of predialysis potassium and phosphorus levels are not affected. However, nutritional status, measured by serum albumin level, tends to be poorer in the alcoholic group.