PubMed Health⌕ Search

Biomedical subjects

J C Buckner

Publications and source records attributed to J C Buckner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma.

PURPOSE: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high-grade glioma. Pharmacokinetic studies of oral etoposide were also done. METHODS AND MATERIALS: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m2 days 1-3, cisplatin 30 mg/m2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29-42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m2 every 8 weeks x 4 cycles was given after radiation therapy. RESULTS: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose-limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m2 days 1-3, cisplatin 20 mg/m2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 microg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean +/- SD 2 hr and 6 hr plasma concentrations were 0.92 +/- 0.43 microg/ml and 0.36 +/- 0.12 microg/ml, respectively. Estimated duration of exposure to >0.1 microg/ml etoposide was 10-17 hr. CONCLUSIONS: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high-grade gliomas is feasible and merits further investigation. Sustained radiosensitizing concentrations can be achieved with low oral doses of etoposide.

Adult↗
PubMed1998

Management of recurrent meningeal hemangiopericytoma.

BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high propensity for recurrence. The purpose of this study was to analyze the efficacy of different treatment options in patients with recurrent disease. METHODS: The records of all patients with recurrent meningeal hemangiopericytoma treated at the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four consecutive patients were studied. The mainstay of treatment was brain surgery in 21 patients (62%); the median time to recurrence from surgery was 12 months. Ten patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all with lesion size < 25 mm) achieved a complete response, which persisted at a median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a median duration of 12 months, whereas 3 lesions (15%) remained stable. Two patients with inoperable CNS lesions received external beam radiation therapy and both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received radiation therapy for metastatic disease. Of these, seven patients remained stable with good symptomatic relief, and two patients experienced tumor progression. Chemotherapy with doxorubicin-containing regimens was administered in 7 patients (21%); there was only 1 PR that lasted 8 months. The median survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is important for the successful treatment of patients with recurrent meningeal hemangiopericytoma. Radiosurgery plays a definite role in the treatment of smaller recurrent CNS lesions. Radiation therapy is helpful in the management of inoperable tumors. More effective chemotherapeutic agents are needed.

Adult↗
PubMed1998

Phase I evaluation of radiation combined with recombinant interferon alpha-2a and BCNU for patients with high-grade glioma.

PURPOSE: A Phase I study to determine the safety, toxicity, and maximum tolerated dose (MTD) of carmustine (BCNU) and interferon alpha-2a (IFN-a) when combined with radiation as initial therapy in high-grade glioma. METHODS AND MATERIALS: Patients with newly diagnosed Grade 3 or 4 astrocytoma, oligoastrocytoma, or gliosarcoma were enrolled after surgery. All received radiation therapy to the brain (64.8 Gy/36 fractions), combined with a single dose of BCNU (200 mg/m2) at the start of radiation. Chemotherapy after completing radiation consisted of BCNU 150 mg/m2 once every 7 weeks, and IFN-a 12 x 10(6) units/m2 subcutaneously Days 1-3 each week of a 7-week cycle. Subsequent dose modification was based on constitutional symptoms for IFN-a and on myelosuppression for BCNU. RESULTS: Fifteen patients were entered on the study. Four were excluded because they did not receive IFN-a (3 refused treatment and 1 patient left the study due to multiple medical problems). Eleven were evaluable for toxicity and efficacy. Nonhematological toxicity, mainly lethargy and flu-like symptoms, were dose-limiting for IFN-a. After the first 6 patients were treated per the initial protocol, the frequency of IFN-a administration was decreased to Days 1-3 on weeks 1, 3, and 5 of the 7-week cycle for 5 additional patients. Lethargy, fever, chills, myalgias, alopecia, and anorexia occurred in all patients. Other toxicities included nausea and vomiting (91%), central-nervous-system depression or mood changes (64%), headaches (55%), and elevation of liver enzymes (36%). Grade 3-4 leukopenia occurred in 4 (45%) of 11 patients, and Grade 3-4 thrombocytopenia in 3 (27%) of 11 patients. Due to myelosuppressive effects, BCNU dose was not escalated. Median survival of the cohort was 44 months. Objective responses occurred in 5 (56%) of 9 patients and median duration of response was 33 months. The MTD of this combination after radiation therapy is IFN-a 12 x 10(6) units/m2 Days 1-3, on Weeks 1, 3, and 5 of a 7-week cycle and BCNU 150 mg/m2 Day 1, every 7 weeks. CONCLUSIONS: Treatment with radiation, IFN-a, and BCNU is feasible and effective in patients with high-grade gliomas, although constitutional symptoms from IFN-a are substantial.

Adult↗
PubMed1998

Phase II trial of recombinant interferon-alpha-2a and eflornithine in patients with recurrent glioma.

Interferons alpha and beta have been reported to cause tumor regression in a small proportion of patients with recurrent glioma. Eflornithine, an irreversible inhibitor of ornithine decarboxylase, reduces cellular polyamine levels and has also been reported to cause tumor regression in patients with recurrent anaplastic astrocytoma and glioblastoma multiforme. In vitro evidence suggests that interferon and eflornithine are synergistic. In this phase II trial, we investigated the combination of recombinant alpha interferon (36 x 10(6) units/m2 subcutaneously days 3 to 7) and eflornithine (2.25 g/m2 QID PO days 1 to 7) repeated every 28 days. All 29 patients entered in the study were evaluable for toxicity and efficacy. Toxicity consisted primarily of fever, chills, myalgia, weakness and fatigue as well as cortical dysfunction including somnolence, confusion, and exacerbation of underlying neurologic deficits. One patient died from cerebral herniation attributable to interferon. None of the patients experienced objective tumor regression. Seven patients (24%) were stable for more than six months, but the disease stability could also be explained by indolent underlying disease or inability to distinguish recurrent tumor from delayed radiation effects. Intermittent high-dose recombinant interferon alpha plus eflornithine demonstrated no definite antitumor effects in this trial.

Adult↗
PubMed1998

Chemotherapy for advanced esthesioneuroblastoma: the Mayo Clinic experience.

OBJECTIVE: Esthesioneuroblastoma (olfactory neuroblastoma) is a rare neuroendocrine tumor that arises in the upper nasal cavity from the olfactory epithelium. Little information is available regarding the treatment of these tumors with chemotherapy in the advanced setting. A retrospective review of patients with recurrent esthesioneuroblastoma treated with chemotherapy between 1970 and 1995 at the Mayo Clinic was undertaken to gain more information regarding the efficacy of chemotherapy treatment for these patients. METHODS: Ten patients were identified using a computerized data base available at this institution. The clinical and pathological materials, when available, were reviewed, and each tumor reviewed was assigned a Hyams' grade. RESULTS: There were six men and four women, ranging in age from 22 to 74 years, all of whom had assessable Kadish Stage C disease at the time of chemotherapy treatment. The chemotherapy regimens and clinical follow-up varied during this 25-year time span. The only tumor regression resultant from chemotherapy was observed in patients with high-grade tumors. Two of four patients with high-grade tumors obtained regression from first-line, platinum-based chemotherapy, with a mean duration of regression of 9.3 months (range, 2-13 mo). Survival time from initial diagnosis was 139.5 months (range, 83-168 mo) in patients with low-grade tumors and 32.2 months (range, 5-84 mo) in patients with high-grade tumors. Survival from initial chemotherapy treatment was 44.5 months (range, 3-130 mo) in patients with low-grade tumors and 26.5 months (range, 2-67 mo) in patients with high-grade tumors. CONCLUSION: Hyams' grading of esthesioneuroblastoma tumors seems to be important in predicting response to chemotherapy. Despite sensitivity to platinum-based chemotherapy, patients with high-grade tumors in this series had a much more aggressive course than did those with lower-grade tumors. This series suggests that cisplatin-based chemotherapy is active in advanced, high-grade esthesioneuroblastoma and is a reasonable choice in the systemic treatment of these patients.

Adult↗
PubMed1998

Prevalence of mental health and substance use disorders among homeless and low-income housed mothers.

OBJECTIVE: This study compared the prevalence of DSM-III-R disorders among homeless and low-income housed mothers with the prevalence of these disorders among all women in the National Comorbidity Survey. METHOD: The authors used an unmatched case-control design for assessing 220 homeless and 216 housed mothers receiving public assistance. RESULTS: Homeless and housed mothers had similar rates of psychiatric and substance use disorders. Both groups had higher lifetime and current rates of major depression and substance abuse than did all women in the National Comorbidity Survey. Both groups also had high rates of posttraumatic stress disorder and two or more lifetime conditions. CONCLUSIONS: The prevalence of trauma-related disorders among poor women was higher than that among women in the general population. Programs and policies designed for low-income mothers must respond to the high prevalence of DSM-III-R disorders.

Case-Control Studies↗
PubMed1998

Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma.

PURPOSE: The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials. METHODS: We studied 701 high-grade brain tumor patients entered onto two consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and physical function over time. Patients who did not demonstrate tumor progression within 60 days of the assessment time were considered nonprogressors at that evaluation. A loss of greater than 3 points on the MMSE was considered significant deterioration. RESULTS: The number of patients who experienced a greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54 nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30 nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22 nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times overlapped, which indicates no statistically significant increase in the percentage of patients who experienced a significant decrease in their MMSE score. Patients who demonstrated a significant decrease in their MMSE score were significantly older than those who did not (P = .0017) at 6 months and remained so throughout follow-up; moreover, they had a significantly shorter time to progression and death. ECOG PS was strongly negatively correlated with MMSE score throughout the study, and MMSE score at all time intervals was correlated with baseline PS. CONCLUSION: In this population of glioma patients who received radiotherapy, there is no clear trend to cognitive worsening. Factors such as older age, poorer PS, and subclinical tumor progression may be more significant factors in those patients who did demonstrate a significant cognitive decline.

Adolescent↗
PubMed1998

Phase II trial of nitrogen mustard, vincristine, and procarbazine in patients with recurrent glioma: North Central Cancer Treatment Group results.

PURPOSE: Previous investigators have reported responses in 52% of patients treated with mechlorethamine (nitrogen mustard), vincristine, and procarbazine (MOP) for recurrent glioma. To confirm these promising results, we conducted a phase II prospective study. PATIENTS AND METHODS: Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen. Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2, respectively, intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8, and procarbazine 100 mg/m2 orally on days 1 to 14. Cycles were repeated every 28 days. RESULTS: Of 61 patients assessable for response, eight responded (13%), with one complete response (CR). Responses were as follows: low-grade gliomas, 19%; anaplastic astrocytomas, 11%; anaplastic oligodendrogliomas or oligoastrocytomas, 25%; and glioblastomas, 4.3%. The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23% and platelet nadirs less than 25,000/microL in 13% of patients. Two patients died of infection in the setting of neutropenia. Nonhematologic toxicity included neurosensory changes in 21% of patients (severe in 3%) and severe dermatologic reactions in 8%. In multivariate analysis, Eastern Cooperative Oncology group (ECOG) performance status (PS) was the best predictor for response to chemotherapy (P=.01) and time to progression (P=.008), while PS and grade were the most important predictors of survival (P=.002 and .05, respectively). CONCLUSION: This study did not confirm the high response rate previously reported in recurrent gliomas. Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low-grade gliomas had the highest response rates (25% and 19%, respectively). In multivariate analysis, ECOG PS was the best predictor of response, while PS and tumor grade were the most important predictors of survival.

Adult↗
PubMed1998

The developmental status and adaptive behavior of homeless and low-income housed infants and toddlers.

OBJECTIVES: This study describes the development status of 127 homeless and 91 low-income housed infants and toddlers. METHODS: The Bayley Scales of Infant Development and the Vineland Screener were used to gather data. RESULTS: There were no differences between homeless and low-income housed children. However, younger children in both groups performed better than the older children on most summary scores. CONCLUSIONS: Homeless and low-income housed children did not differ in their cognitive and motor skills. However, older children scored lower than younger children on most measures of development status, suggesting that the cumulative effects of poverty may increase with time.

Adaptation, Psychological↗
PubMed1998

Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results.

OBJECT: Gliosarcoma, a rare malignancy of the central nervous system, consists of gliomatous and sarcomatous elements. There are conflicting reports regarding its aggressiveness and cell line of origin compared with those of glioblastoma multiforme (GBM). The goal of this study was to compare clinicopathological features such as disease-free survival time and actual survival time in patients with gliosarcoma with a matched group of patients with GBM as well as with the entire group of patients with GBM. METHODS: The authors report on 18 cases of gliosarcoma derived from a series of 748 Grade 4 astrocytoma cases that were part of four consecutive randomized Phase III trials conducted between 1979 and 1996. In this series the gliosarcoma group represented only 2.4% of all GBMs and included 11 men and seven women with a median age of 61.5 years (range 31-81 years). The median tumor size was 5 cm (range 2-8 cm). The locations, all supratentorial, included temporal in 44%, parietal in 28%, frontal in 17%, and occipital in 11%. The 18 patients with gliosarcomas, all Grade 4 (World Health Organization classification), were compared with the entire group of 730 patients with GBM and a control group of 18 patients with GBM matched for known prognostic factors including patient age, randomization date, performance status, extent of resection, and protocol number. Patients in all treatment groups received radiation and nitrosourea-based chemotherapy. The median time to progression and the median survival times for the patients with gliosarcoma were 28.0 and 35.1 weeks as compared with 24.7 and 41.6 weeks for the entire group of patients with GBM (log rank test, p = 0.94 and 0.27, respectively) and 16.7 and 34.4 weeks in the control group (p = 0.20 and 0.84, respectively). In previous molecular cytogenetic analyses of gliosarcoma these authors have shown similar genetic changes in the gliomatous and sarcomatous components. CONCLUSIONS: The data obtained in this study support the conclusion that gliosarcoma shares significant clinical and genetic similarities with GBM and that the same principles should be applied for patient enrollment in research protocols and treatment for these two kinds of tumor.

Adult↗
PubMed1998

Displaced children: meeting the health, mental health, and educational needs of immigrant, migrant, and homeless youth.

A growing number of children of all ages are experiencing homelessness and displacement. This chapter explores the needs of displaced children in the U.S., focusing on children of immigrants, children from families of migrant farmworkers, and homeless youth. The author discusses many of the common challenges and needs of displaced youth, but also points out the differences between younger children and adolescents, followed by a set of recommendations for health care and service providers.

Adolescent↗
PubMed1997

Mental disorders and service utilization among youths from homeless and low-income housed families.

OBJECTIVE: To assess the mental health of homeless and poor housed youths, using the National Institute of Mental Health (NIMH) Diagnostic Interview Schedule for Children (DISC) Version 2.3, and to examine mental health service use. METHOD: As part of a comprehensive study of homeless and housed families Worcester, MA, data were collected on 41 homeless and 53 poor housed (never homeless) youths aged 9 to 17 using both the parent and youth versions of the DISC. RESULTS: On the basis of the parent version of the DISC, current (6-month) prevalence rates of DSM-III-R disruptive behavior, affective, and anxiety disorders were comparable in homeless and housed youths but higher than rates found among youths in the NIMH-sponsored Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study, which used the same diagnostic measure. Approximately 32% of the combined sample of homeless and housed youths had a current mental disorder accompanied by impairment in functioning. Mental health service use in the preceding 6 months among youths who had one or more current disorders and associated impairment ranged from 20% to 35%. A subgroup of youths with one or more current disorders and poor global functioning had never received treatment. CONCLUSIONS: This sample of homeless and housed youths was found to have high rates of current mental disorders. Use of mental health services by children with mental health needs was low, particularly for youths with poor overall functioning.

Adolescent↗
PubMed1997

Effective chemotherapy for advanced CNS embryonal tumors in adults.

PURPOSE: Embryonal tumors of the CNS include, among others, medulloblastoma, cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors (PNETs). Almost all data on the treatment of embryonal CNS tumors are derived from the pediatric population, since these tumors are uncommon in adulthood. The purpose of this study was to examine the rate and duration of response to chemotherapy of advanced embryonal CNS tumors in adults. PATIENTS AND METHODS: We retrospectively studied all adult (> 18 years of age) patients with advanced embryonal tumors of the CNS who received chemotherapy at our institution between 1976 and 1994. Seventeen consecutive patients were treated with regimens that contained either nitrosourea or cisplatin or both sequentially, with no patients having received the combination of nitrosourea and cisplatin concurrently. RESULTS: In patients who received cisplatin-based chemotherapy, responses were observed in 84.5% (26% complete response [CR] rate), 10.5% remained stable, and 5% progressed. The median time to progression was 18 months for patients who had a CR, 6 months for those with partial response (PR), and 10 months for stable patients. Among patients who received nitrosourea-based chemotherapy, PR was observed in 27%, 36.5% remained stable, and 36.5% progress. The median time to progression was 6 months for patients who had a PR and 6.5 months for stable patients. CONCLUSION: In adults with advanced embryonal CNS tumors, conventional-dose intravenous cisplatin-based chemotherapy regimens are able to produce responses in the majority of the patients (84.5%), even as second- or third-line regimens. Nitrosourea-based regimens less frequently produce responses (27%).

Adolescent↗
PubMed1997

Determinants of behavior in homeless and low-income housed preschool children.

OBJECTIVES: To describe the characteristics of homeless and low-income preschool-aged children, and to identify family and environmental determinants of their behavior. METHODS: An unmatched case-control design was used to recruit a sample of sheltered homeless families and a comparison group of low-income housed families who were never homeless in Worcester, Massachusetts. Seventy-seven sheltered homeless and 90 low-income housed mothers with preschool-age children were assessed using a comprehensive interview protocol. Information about mothers' housing, income, service use, par-enting practices, and children's father was obtained. Data about children's background, health, and life events were included. Standardized instruments were administered to assess mothers' mental health and their children's behavior. Comparisons of homeless and low-income housed families were used to describe the sample of 167 preschoolers. Multiple linear regression was used to examine the association of various stressors, such as homelessness, and family factors with their behavior. RESULTS: Although homeless preschoolers were significantly more likely to have experienced stressful life events, undergone a care and protection investigation, and been placed in foster care when compared with low income preschoolers, differences in adverse behaviors were minimal. Although homeless children scored higher than housed children on the internalizing, externalizing, and total problem score on the Child Behavior Checklist (CBCL) (52.5 vs 49.9, 54.8 vs 51.2, and 54.4 vs 51.1, respectively), approximately equal numbers of children from both groups scored in the clinical range. With regard to determinants of behavior, mothers' emotional status was one of the strongest independent predictors of negative behavioral outcomes on both subscales. Foster care placement and death of a child's friend were predictors of adverse internalizing behavioral outcomes on the CBCL. After controlling for housing status, parenting practices, child's age, child's history of physical abuse, and specific life stressors predicted adverse externalizing behavioral outcomes. For both subscales, housing status and behavior were only marginally associated in the multivariate model. CONCLUSIONS: Both homeless and low-income children experienced significant adversity in their lives, with homeless preschool children facing more stress. However, differences in behavior as measured by the CBCL were minimal. Mothers' emotional status, in addition to various stressors, strongly predict children's negative outcomes for both CBCL subscales. These findings emphasize the importance of preventive family-oriented interventions that address the needs of preschoolers and their mothers.

Black or African American↗
PubMed1997

Homelessness in female-headed families: childhood and adult risk and protective factors.

OBJECTIVES: To identify risk and protective factors for family homelessness, a case-control study of homeless and low-income, never-homeless families, all female-headed, was conducted. METHODS: Homeless mothers (n = 220) were enrolled from family shelters in Worcester, Mass. Low-income housed mothers receiving welfare (n = 216) formed the comparison group. The women completed an interview covering socioeconomic, social support, victimization, mental health, substance use, and health domains. RESULTS: Childhood predictors of family homelessness included foster care placement and respondent's mother's use of drugs. Independent risk factors in adulthood included minority status, recent move to Worcester, recent eviction, interpersonal conflict, frequent alcohol or heroin use, and recent hospitalization for a mental health problem. Protective factors included being a primary tenant, receiving cash assistance or a housing subsidy, graduating from high school, and having a larger social network. CONCLUSIONS: Factors that compromise an individual's economic and social resources are associated with greater risk of losing one's home.

Adolescent↗
PubMed1997

Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer.

Temozolomide (TMZ) is a new imidazotetrazine derivative with early clinical activity in glioma and melanoma. The purpose of this Phase I study is to characterize the toxicity, pharmacokinetics, and antitumor activity of TMZ administered on an oral 5-day schedule to patients with or without prior exposure to nitrosourea (NU). Thirty-six eligible patients received a total of 77 cycles of therapy with TMZ administered p.o. at doses ranging from 50 mg/m2/day to 250 mg/m2/day for 5 days, every 4 weeks. Separate dose escalations were carried out in patients, with or without prior exposure to NU. Pharmacokinetic studies were performed during the first cycle of treatment on days 1 and 5. Dose-limiting toxicity was thrombocytopenia, and the maximally tolerated doses for patients with and without prior exposure to NU were 150 mg/m2/day for 5 days (total dose, 750 mg/m2) and 250 mg/m2/day for 5 days (total dose, 1250 mg/m2), respectively. Significant (grade 3 or higher) thrombocytopenia was observed in six patients during cycle 1. The median times to nadir and recovery were 17 and 15 days, respectively. Nonhematological toxicity was generally manageable and consisted of fatigue, nausea, and vomiting. There were two complete responses (one glioma and one melanoma) in patients without prior NU. No objective responses were seen in patients with prior NU treatment. Pharmacokinetic studies showed rapid absorption with a mean time to peak concentration of 60 min and mean t1/2 of 109 min (range, 80-121 min). The area under the curve and the peak plasma concentrations were linear over the dose range of 50-250 mg/m2/day. The mean apparent oral clearances on day 1 for patients with and without prior NU exposure were 102+/- 27 and 115+/- 22 ml/min/m2, respectively. Apparent oral clearances on days 1 and 5 were found to differ with respect to NU exposure (P = 0.047). Renal clearance of the parent drug and its metabolism to 3-methyl-2, 3-dihydro-4-oxoimidazo[5,1-d]tetrazine-8-carboxylic acid were minor pathways of TMZ elimination. We conclude that TMZ is well tolerated in this oral 5-day schedule with dose-limiting thrombocytopenia and that it has promising activity in glioma and melanoma. The recommended doses for Phase II studies in patients with and without prior NU are 125 mg/m2/day for 5 days and 225 mg/m2/day for 5 days, respectively.

Administration, Oral↗
PubMed1996

The characteristics and needs of sheltered homeless and low-income housed mothers.

OBJECTIVE: To compare characteristics of homeless and low-income housed mothers across economic, psychosocial, and physical health domains. DESIGN: Case-control study. SETTING: Community of Worcester, Mass. PARTICIPANTS: A cross-sectional sample of 220 sheltered homeless mothers and 216 low-income housed (never homeless) mothers receiving welfare. MAIN OUTCOME MEASURES: Income, housing, life events, social support, history of abuse and assault, and mental and physical health. RESULTS: Comparison of homeless and housed mothers revealed some important similarities and differences. The proportion of homeless mothers with annual incomes of less than $7000 was 46% vs 17% for housed mothers (P<.O1). Homeless mothers experienced more residential instability than the housed mothers (3.8 moves vs 1.8 moves; P<.001) and had smaller support networks (P<.001). More homeless mothers reported severe physical and sexual assault over the lifespan than housed mothers (91.6% vs 81.1 %; P<.003). No significant differences were found between the groups in mental and physical health. However, the lifetime prevalence of major depressive disorder, posttraumatic stress disorder, and substance use disorders was overrepresented compared to the general female population. Both groups had lower physical functioning compared to the general population and a higher prevalence of chronic health conditions. CONCLUSIONS: Sheltered homeless mothers had fewer economic resources and social supports and higher cumulative rates of violent abuse and assault over their lifespans than their housed counterparts. However, both groups faced extreme adversity that compromised family well-being. Practitioners and social policymakers need to be cognizant of the multiple economic, psychosocial, and physical health needs of these mothers in providing treatment and developing program interventions.

Adolescent↗