A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity.

BACKGROUND: Isolated limb infusion with melphalan (ILI-M) corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response (CR) rate. Sorafenib, a multi-kinase inhibitor, has been shown to augment tumor response to chemotherapy in preclinical studies. METHODS: A multi-institutional, dose-escalation, phase I study was performed to evaluate the safety and antitumor activity of sorafenib in combination with ILI-M. Patients with AJCC stage IIIB/IIIC/IV melanoma were treated with sorafenib starting at 400 mg daily for 7 days before and 7 days after ILI-M corrected for IBW. Toxicity, drug pharmacokinetics, and tumor protein expression changes were measured and correlated with clinical response at 3 months. RESULTS: A total of 20 patients were enrolled at two institutions. The maximum tolerated dose (MTD) of sorafenib in combination with ILI-M was 400 mg. Four dose-limiting toxicities occurred, including soft tissue ulcerations and compartment syndrome. There were three CRs (15 %) and four partial responses (20 %). Of patients with the Braf mutation, 83 % (n = 6) progressed compared with only 33 % without (n = 12). Short-term sorafenib treatment did alter protein expression as measured with reverse phase protein array (RPPA) analysis, but did not inhibit protein expression in the MAP kinase pathway. Sorafenib did not alter melphalan pharmacokinetics. CONCLUSION: This trial defined the MTD of systemically administered sorafenib in combination with ILI-M. Although some responses were seen, the addition of sorafenib to ILI-M did not appear to augment the effects of melphalan but did increase regional toxicity.

Impact of therapy With chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup Study Cancer and Leukemia Group B 9011.

PURPOSE: We sought to determine whether therapy with single-agent fludarabine compared with chlorambucil alone or the combination of both agents had an impact on the incidence and spectrum of infections among a series of previously untreated patients with B-cell chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Five hundred fifty-four previously untreated CLL patients with intermediate/high-risk Rai-stage disease were enrolled onto an intergroup protocol. Patients were randomized to therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil. Data pertaining to infection were available on 518 patients. Differences in infections among treatment arms were tested with the Kruskal-Wallis, Wilcoxon, and chi(2) tests. RESULTS: A total of 1,107 infections (241 major infections) occurred in 518 patients over the infection follow-up period (interval from study entry until either reinstitution of initial therapy, therapy with a second agent, or death). Patients treated with fludarabine plus chlorambucil had more infections than those receiving either single agent (P <.0001). Comparing the two single-agent arms, there were more infections on the fludarabine arm (P =.055) per month of follow-up. Fludarabine therapy was associated with more major infections and more herpesvirus infections compared with chlorambucil (P =.008 and P =.004, respectively). Rai stage and best response to therapy were not associated with infection. A low serum immunoglobulin G was associated with number of infections (P =.02). Age was associated with incidence of major infection in the combination arm (P =.004). CONCLUSION: Combination therapy with fludarabine plus chlorambucil resulted in significantly more infections than treatment with either single agent. Patients receiving single-agent fludarabine had more major infections and herpesvirus infections compared with chlorambucil-treated patients.

Use and cost of outpatient visits of AD patients: CERAD XXII.

OBJECTIVE: To determine the probability, frequency, and cost of outpatient visits of patients with AD in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) as a function of stage of dementia and institutional status. METHODS: Clinical information on 388 patients with AD enrolled in CERAD who had no serious comorbidities at baseline and for whom the stage of disease and institutional status were known, were linked to Health Care Financing Administration Physician/Supplier and Outpatient Standard Analytic (institutional outpatient) files for 1991 through 1995. None was registered in a health maintenance organization. Repeated measures regression models were used to examine the relationship of stage of disease to probability, frequency, and cost of outpatient visits for institutionalized and noninstitutionalized patients, with demographic characteristics and calendar time controlled. RESULTS: The annual proportion of patients with AD and a Medicare-reimbursed outpatient visit ranged from 81% to 95% and was not related to stage of dementia or institutional status. Among those with at least one outpatient visit, however, those living at home had fewer visits than did those in institutions, but their number of visits increased as dementia worsened. Those in institutions had a larger number of outpatient visits, but these did not vary significantly by stage of dementia. Neither location of residence nor stage affected the cost of outpatient visits. CONCLUSION: Among those with an outpatient visit, the frequency of visits and their relationship to stage of disease depends on institutional status.

Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy.

PURPOSE: Weight gain is a common problem among breast cancer patients who receive adjuvant chemotherapy (CT). We undertook a study to determine the causes of this energy imbalance. PATIENTS AND METHODS: Factors related to energy balance were assessed at baseline (within 3 weeks of diagnosis) and throughout 1 year postdiagnosis among 53 premenopausal women with operable breast carcinoma. Thirty-six patients received CT and 17 received only localized treatment (LT). Measures included body composition (dual energy x-ray absorptiometry), resting energy expenditure (REE; indirect calorimetry), dietary intake (2-day dietary recalls and food frequency questionnaires) and physical activity (physical activity records). RESULTS: Mean weight gain in the LT patients was 1.0 kg versus 2.1 kg in the CT group (P =.02). No significant differences between groups in trend over time were observed for REE and energy intake; however, a significant difference was noted for physical activity (P =.01). Several differences between groups in 1-year change scores were detected. The mean change (+/- SE) in LT versus CT groups and P values for uncontrolled/controlled (age, race, radiation therapy, baseline body mass index, and end point under consideration) analysis are as follows: percentage of body fat (-0.1 +/- 0.4 v +2.2 +/- 0.6%; P =.001/0.04); fat mass (+0.1 +/- 0.3 v +2.3 +/- 0.7 kg; P =.002/0.04); lean body mass (+0.8 +/- 0.2 v -0.4 +/- 0.3 kg; P =.02/0.30); and leg lean mass (+0.5 +/- 0.1 v -0.2 +/- 0.1 kg; P =.01/0.11). CONCLUSION: These data do not support overeating as a cause of weight gain among breast cancer patients who receive CT. The data suggest, however, that CT-induced weight gain is distinctive and indicative of sarcopenic obesity (weight gain in the presence of lean tissue loss or absence of lean tissue gain). The development of sarcopenic obesity with evidence of reduced physical activity supports the need for interventions focused on exercise, especially resistance training in the lower body, to prevent weight gain.

Use and cost of hospitalization of patients with AD by stage and living arrangement: CERAD XXI.

OBJECTIVE: To determine the probability, frequency, length of stay, and Medicare costs of hospitalization of institutionalized and noninstitutionalized patients with AD at various stages of dementia. METHODS: The authors analyzed the 1991 to 1995 Medicare records of 420 CERAD patients with AD, a group which, at entry, had no serious comorbidities. They were geographically distributed across the United States and observed for a median of 2.5 years. Repeated measures logistic regression and generalized estimating equations were used to model the probability of hospitalization. Among those hospitalized, the general linear mixed model was used to determine number of admissions, length of stay, and Medicare cost. Demographic characteristics and calendar date were controlled in all analyses. RESULTS: As dementia worsened, the probability of hospitalization increased among patients living at home, but decreased among those who were institutionalized. Number of admissions, length of stay, and cost also decreased significantly as stage worsened among the institutionalized patients, but the stage of dementia had no effect in non-institutionalized patients. CONCLUSION: The hospitalization experience of patients with AD living at home differs from that of patients with AD living in institutions. Residential setting appears to be an important determinant of hospitalization in patients with AD.

Detecting treatment-by-centre interaction in multi-centre clinical trials.

This paper considers several permutation tests for treatment-by-centre interaction in multi-centre clinical trials in which the endpoint is survival time subject to censoring. Some of the tests are based on existing tests and some are new. To evaluate and compare the tests with respect to power under different conditions, we generated survival times and censoring times through simulation. We used special methodology to handle the unusual problems that arise in power simulations when the tests under study are permutation tests. Different conditions yielded different interaction tests as the best performers. Although one test gave comparatively good power under almost all conditions, some of the other tests also appear to be useful. For the sample sizes and configurations in the simulations, power is generally low; thus it may not be possible to detect interaction reliably when it exists, a finding in agreement with the known low power for interaction tests in general.

Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia.

BACKGROUND: Fludarabine is an effective treatment for chronic lymphocytic leukemia that does not respond to initial treatment with chlorambucil. We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia. METHODS: Between 1990 and 1994, we randomly assigned 509 previously untreated patients with chronic lymphocytic leukemia to one of the following treatments: fludarabine (25 mg per square meter of body-surface area, administered intravenously daily for 5 days every 28 days), chlorambucil (40 mg per square meter, given orally every 28 days), or fludarabine (20 mg per square meter per day for 5 days every 28 days) plus chlorambucil (20 mg per square meter every 28 days). Patients with an additional response at each monthly evaluation continued to receive the assigned treatment for a maximum of 12 cycles. RESULTS: Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone. Among the other two groups, the response rate was significantly higher for fludarabine alone than for chlorambucil alone. Among 170 patients treated with fludarabine, 20 percent had a complete remission, and 43 percent had a partial remission. The corresponding values for 181 patients treated with chlorambucil were 4 percent and 33 percent (P< 0.001 for both comparisons). The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months, respectively, whereas both values were 14 months in the chlorambucil group (P<0.001 for both comparisons). The median overall survival among patients treated with fludarabine was 66 months, which was not significantly different from the overall survival in the other two groups (56 months with chlorambucil and 55 months with combined treatment). Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil (P=0.08), although, overall, toxic effects were tolerable with the two single-drug regimens. CONCLUSIONS: When used as the initial treatment for chronic lymphocytic leukemia, fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil.

Psychological impact of diagnosis and risk reduction among cancer survivors.

Life-threatening health events prompt psychological distress that may motivate individuals to reduce health risks. If so, interventions timed to take advantage of these 'teachable moments' could be particularly effective. To explore this association, early stage prostate and breast cancer patients were identified from a hospital-based tumor registry within 6 years of diagnosis. These patients (n=920) completed a mailed survey assessing the Horowitz impact of events scale, risk behaviors and readiness to change the behaviors. Breast cancer patients, younger patients and those reporting poor health status reported the greatest impact of the cancer diagnosis. Impact was inversely associated with time from diagnosis for prostate, but not breast cancer patients. Prostate patients who reported exercising regularly had lower impact scores than those who were not exercising (medians: 0.13 vs 0.56, respectively; p=0.02). Breast patients who were eating five or more fruits and vegetables reported lower impact scores than those who were not eating the recommended servings (0.75 vs 1.06, respectively; p=0.03). Breast patients who were non-smokers reported lower impact scores than smokers (0.88 vs 1.31, respectively; p=0. 02). Prospective studies are needed to understand the psychological impact of cancer diagnosis and how it might facilitate or impede the adoption of health promoting behaviors.

World population data for the HLA-DQA1, PM and D1S80 loci with least and most common profile frequencies for combinations of loci estimated following NRC II guidelines.

All published and unpublished gene frequency data for the PCR-based loci HLA-DQA1, LDLR, GYPA, HBGG, D7S8, GC, and D1S80 that could be located are presented in summary tables. These gene frequencies provide the data necessary for estimating probabilities of chance match according to NRC II guidelines for any DNA profile that includes any combination of these loci for any of the populations. To illustrate the range of polymorphism for combined locus profiles, least and most common profile frequencies were estimated following NRC II guidelines for: the PM loci for all populations for which PM data were available; and for combinations of HLA-DQA1/PM, HLA-DQA1/D1S80, PM/D1S80, and HLA-DQA1/ PM/D1S80 for populations for which data were available for the relevant combinations. The profile frequencies were calculated at theta values of zero and 0.01. Minimum allele frequencies (MAF) were calculated, and are shown, for each data set for which the MAF was greater than the lowest observed allele frequency. Least common profile frequencies were calculated using MAF in those cases to illustrate a conservative estimate. The effect of using MAF versus lowest observed allele frequency in estimating least common profile frequencies is briefly illustrated as well. We finally show that aggregate U.S. gene frequency data for the classical MN and GC polymorphisms for both Caucasian and African-American populations is fully in accord with the DNA-based gene frequency data obtained from PM reverse dot-blot strips for GYPA and GC, respectively.

Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization. A randomized, controlled trial.

BACKGROUND: Control of hyperglycemia delays or prevents complications of diabetes, but many persons with diabetes do not achieve optimal control. OBJECTIVE: To compare diabetes control in patients receiving nurse case management and patients receiving usual care. DESIGN: Randomized, controlled trial. SETTING: Primary care clinics in a group-model health maintenance organization (HMO). PATIENTS: 17 patients with type 1 diabetes mellitus and 121 patients with type 2 diabetes mellitus. INTERVENTION: The nurse case manager followed written management algorithms under the direction of a family physician and an endocrinologist. Changes in therapy were communicated to primary care physicians. All patients received ongoing care through their primary care physicians. MEASUREMENTS: The primary outcome, hemoglobin A1c (HbA1c) value, was measured at baseline and at 12 months. Fasting blood glucose levels, medication type and dose, body weight, blood pressure, lipid levels, patient-perceived health status, episodes of severe hypoglycemia, and emergency department and hospital admissions were also assessed. RESULTS: 72% of patients completed follow-up. Patients in the nurse case management group had mean decreases of 1.7 percentage points in HbA1c values and 43 mg/dL (2.38 mmol/L) in fasting glucose levels; patients in the usual care group had decreases of 0.6 percentage points in HbA1c values and 15 mg/dL (0.83 mmol/L) in fasting glucose levels (P < 0.01). Self-reported health status improved in the nurse case management group (P = 0.02). The nurse case management intervention was not associated with statistically significant changes in medication type or dose, body weight, blood pressure, or lipids or with adverse events. CONCLUSIONS: A nurse case manager with considerable management responsibility can, in association with primary care physicians and an endocrinologist, help improve glycemic control in diabetic patients in a group-model HMO.

Cerebral infarcts in patients with autopsy-proven Alzheimer's disease: CERAD, part XVIII. Consortium to Establish a Registry for Alzheimer's Disease.

OBJECTIVE: To study the relation between cerebral infarction and clinical and neuropsychologic manifestations in patients with autopsy-proven Alzheimer's disease (AD) enrolled in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). BACKGROUND: Prior studies report that subjects with neuropathologic evidence of AD and concomitant brain infarcts had poorer cognitive function and higher frequency of dementia than those with AD alone. METHODS: Clinical and neuropsychologic manifestations of dementia were studied in 74 subjects with neuropathologic findings of AD alone and 32 with AD and concomitant cerebral infarcts or lacunar lesions. RESULTS: The 32 patients with both AD and vascular lesions were significantly older at time of death (median age, 81 years) than the 74 patients with AD alone (76 years; p = 0.02). At the final follow-up visit, the severity of the dementia was greater in AD patients with vascular lesions (median Clinical Dementia Rating [CDR] = 3) than in those with AD alone (CDR = 2; p = 0.03). Patients with AD and vascular lesions performed significantly worse on verbal fluency, Boston Naming, and Mini-Mental State Examination (MMSE) tests. No differences between the groups were observed, however, in the semiquantitative measures of frequency of neuritic plaques or neurofibrillary tangles. CONCLUSIONS: The clinical-neuropathologic correlations in CERAD patients generally confirm those in prior studies, indicating that the presence of cerebral infarction in patients with AD is associated with greater overall severity of clinical dementia and poorer performance on specific tests of language and cognitive function.

Religiosity and remission of depression in medically ill older patients.

OBJECTIVE: The effects of religious belief and activity on remission of depression were examined in medically ill hospitalized older patients. METHOD: Consecutive patients aged 60 years or over who had been admitted to medical inpatient services at a university medical center were screened for depressive symptoms. Of 111 patients scoring 16 or higher on the Center for Epidemiologic Studies Depression Scale, 94 were diagnosed with depressive disorder (DSM-III major depression or subsyndromal depression) by a psychiatrist using a structured psychiatric interview. After hospital discharge, depressed patients were followed up by telephone at 12-week intervals four times. At each follow-up contact, criterion symptoms were reassessed, and changes in each symptom over the interval since last contact were determined. The median follow-up time for 87 depressed patients was 47 weeks. Religious variables were examined as predictors of time to remission by means of a multivariate Cox model, with controls for demographic, physical health, psychosocial, and treatment factors. RESULTS: During the follow-up period, 47 patients (54.0%) had remissions; the median time to remission was 30 weeks. Intrinsic religiosity was significantly and independently related to time to remission, but church attendance and private religious activities were not. Depressed patients with higher intrinsic religiosity scores had more rapid remissions than patients with lower scores. CONCLUSIONS: In this study, greater intrinsic religiosity independently predicted shorter time to remission. To the authors' knowledge, this is the first report in which religiosity has been examined as a predictor of outcome of depressive disorder.

Predictors of pain self-report in nursing home residents.

The purpose of this study was to examine the influence of cognitive function and other biopsychosocial factors on test-retest agreement, four-week variability, and intensity of self-reported pain using the verbal 0 to 10 scale and a pain thermometer in 115 nursing home residents over four weeks. Pain was assessed twice on three days during week 1, and once each during weeks 2, 3 and 4. A forward stepwise regression procedure was used to examine the influence of biopsychosocial parameters (age, race, gender, educational status, marital status, comorbidity, cognitive function, depression, social support, physical function and self-rated health) on pain intensity, test-retest agreement and variability. There was a quadratic association between cognitive function and test-retest agreement with the 0-10 scale; residents with Folstein scores of 22-26 were more likely to show disagreement (50% of 34) than residents with scores < 22 or > 26 (7% of 71). Higher Folstein scores were also associated with greater pain intensity for both pain scales (p < 0.001). Baseline pain intensity was significantly related to pain variability (0-10 scale only). The clinician should be cognizant of these relationships when interpreting verbalizations of pain in long-term care facilities.

Depression in medically ill hospitalized older adults: prevalence, characteristics, and course of symptoms according to six diagnostic schemes.

OBJECTIVE: The purpose of this study was to examine and compare rates of depression, correlates, and course of symptoms in medically ill hospitalized elders through use of six diagnostic schemes (inclusive, etiologic, exclusive-inclusive, exclusive-etiologic, substitutive-inclusive, and substitutive-etiologic). METHOD: A consecutive series of 460 cognitively unimpaired patients aged 60 or over who were admitted to the medical inpatient services of Duke Hospital underwent a structured psychiatric evaluation administered by a psychiatrist. Patients with depression were contacted by telephone at 12-week intervals after discharge to assess weekly change in depressive symptoms (median follow-up time = 47 weeks). RESULTS: The prevalence of major depression varied from 10% to 21% depending on diagnostic scheme; similarly, minor depression varied from 14% to 25%. Diagnostic strategy made little difference in known psychological and health characteristics of patients with depression (predictive validity) or severity of depressive symptoms (convergent validity). The diagnostic strategy that best distinguished a severe and persistent major depression was the exclusive-etiologic approach; however, this strategy missed 49% of patients with major depression identified by the inclusive approach, almost 60% of whom continued to experience persistent symptoms of depression many weeks after discharge. CONCLUSIONS: Diagnostic strategy affects rates of major and minor depression, with about a twofold difference between the extremes. There is little reason, however, to choose one diagnostic scheme over another in all cases. Diagnostic strategy should be chosen on the basis of the specific goals and purposes of the examiner. While the exclusive-etiologic approach identifies the most severe and persistent depressions, the inclusive approach is the most sensitive and reliable approach and is an intermediate predictor of persistent depression.

Personality factors differentially predict exercise behavior in men and women.

Personality assessed with the Minnesota Multiphasic Personality Inventory (MMPI) in college was used to predict exercise behavior measured at midlife in 3,630 men and 796 women enrolled in the University of North Carolina Alumni Heart Study. Logistic regression models were fitted for each of the MMPI clinical scales to test the predictive effect of personality, gender, and their interaction on adult exercise behavior. Lower depression, social introversion, and psychopathic deviance scores were associated with increased probability of exercising in midlife for both men and women. Furthermore, better psychological health (indexed by lower hypochondriases and psychasthenia) in college was generally predictive of increased exercise for men, whereas higher scores on these same factors predicted midlife exercise for women. There were two other patterns of gender interactions: (a) for men, lower scores on hysteria and schizophrenia scales were associated with increased probability of exercising at midlife, whereas these factors were unrelated to exercise for women and (b) for women, lower ego strength and higher college scores on paranoia and mania were associated with exercise behavior at midlife. These data suggest that early adulthood personality predictors of exercise behavior at midlife are both gender-neutral and gender-specific; that is, where no gender differences exist, healthier personality traits predict exercise at midlife, and when gender differences do occur, healthier college patterns of personality predict exercise behavior for men and sedentary behavior for women.

Religious coping in the nursing home: a biopsychosocial model.

OBJECTIVE: To examine psychosocial and physical health correlates of religious coping in medically ill chronically institutionalized older adults. Religious coping is defined as the extent to which persons use religious beliefs and practices to help them to cope. METHOD: This is a cross-sectional cohort study conducted in a 120 bed VA-affiliated and a 125 bed university affiliated community-based nursing home in Durham, North Carolina. Participants were 115 chronic care nursing home residents; mean age of the sample was seventy-nine years, 44 percent were women, and 17 percent were African Americans. Subjects were enrolled for a one-month period during which comprehensive psychosocial and health assessments were performed, including evaluation of cognitive function (Mini-Mental State Exam), physical function (Barthel index), severity of medical comorbidity (Cumulative Illness Rating Scale), self-reported physical pain (vertical verbal descriptor scale), depressive symptoms (Geriatric Depression Scale), social support (social network), and religious coping (Religious Coping Index). RESULTS: Over 43 percent of the sample scored in the depressed range of the Geriatric Depression Scale. Almost 60 percent reported they used religion at least to a large extent when coping with their problems; 34 percent said that it was the most important factor that enabled them to cope. Patients who used religion to cope had greater social support (p = .01), more severe medical illness (p = .04), and better cognitive functioning (p = .02). CONCLUSIONS: Religious beliefs and practices are frequently used by chronically institutionalized older adults to help them to cope. Religious coping is associated with more severe medical illness, higher social support, and better cognitive functioning.

Continuous infusion 5-fluorouracil as first-line therapy for metastatic breast cancer.

Previous phase II studies of continuous infusion Fluorouracil (5-FU) (CI 5-FU) in refractory metastatic breast cancer have shown modest activity with low toxicity. Its activity in a first-line setting has not been formally tested. Patients were eligible if they fulfilled the following criteria: metastatic breast cancer; measurable or evaluable disease, no prior chemotherapy in the metastatic setting; ECOG performance status of 0, 1, or 2: adequate bone marrow and liver function. Patients were treated with 5-FU 250 mg/m2 per day by continuous intravenous infusion for 5 weeks in a 6-week cycle. Treatment was continued until disease progression or unacceptable toxicity. In addition to the traditional endpoints of response, survival, and toxicity, quality of life was assessed with the Functional Living Index-Cancer (FLIC) and the Symptom Distress Scale (SDS). Twenty-one patients were enrolled. Among the 16 patients with measurable disease, the objective response rate was 44% (95% CI 20%, 68%) with CR rate 13% and PR rate 31%. The median duration of response was 37 weeks. Responses were not observed in patients with visceral (lung or liver) disease. Among all 21 patients in the study, the median time to disease progression was 12 weeks, and median overall survival was 64 weeks. Grade 1 or 2 mucosal and cutaneous toxicity were common. Only 4 patients (19%) had toxicity greater than grade 2; three patients had grade 3 mucositis, and 1 patient developed an indwelling catheter infection requiring its removal. Among responding patients, mean FLIC scores improved from 114.3 at baseline to 128.7 at week 8 (p = 0.11). Symptoms reported on the SDS generally improved in responding patients. Continuous infusion 5-FU as a first-line therapy for metastatic breast cancer has moderate activity and low toxicity. Its use should be considered in the first-line setting when toxicity needs to be minimized.

A phase II trial of didemnin B in myeloma. A Cancer and Leukemia Group B (CALGB) study.

Didemnin B is a member of a class of compounds, derived from a marine source, undergoing phase II study. Twenty-two patients with relapsed myeloma were treated with didemnin B at an initial dose of 4.9 mg/m2, given once every 28 days. All were evaluable for toxicity, and 15 were evaluable for myeloma response. No tumor regressions occurred in the 15 patients evaluable for response. Vomiting was the major toxicity, occurring in 73% of patients despite vigorous pre- and post-treatment medication with at least three intravenous antiemetics. Two instances of grade 4 hypersensitivity reaction occurred. We conclude that didemnin B has no activity at this dose and schedule in myeloma that has relapsed after one or two prior therapeutic regimens.