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Biomedical subjects

Donna Neuberg

Publications and source records attributed to Donna Neuberg.

At least 55 records · Page 3Linked to original sources
PubMed2004

Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure?

BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with a variable clinical course. Identification of serologic markers associated with increased risk of liver failure would assist in management of PBC patients. The objective of this study was to identify antinuclear antibody (ANA) markers that may be used to predict PBC outcome. METHODS: Indirect immunofluorescence was used to identify ANAs in 492 PBC patients. chi2 and Kaplan-Meier analyses were used to examine the association between ANAs and liver failure. RESULTS: A greater percentage of ANA-positive, compared to ANA-negative, PBC patients developed liver failure (41% vs 25%, P = .005). The presence of anti-centromere antibodies was associated with liver failure (anti-centromere antibody positive vs negative, 58% vs 33%, P = .001). The time to liver failure was shorter in ANA-positive, compared with ANA-negative, patients (log rank score 5.8, P = .02). After 8.9 years (the median follow-up for patients without liver failure), 68% of ANA-positive and 81% of ANA-negative patients were free of liver failure. Anti-centromere antibodies were also associated with a shorter time to liver failure (log rank score 8.4, P = .004). After 8.9 years, 52% of anti-centromere antibody positive and 74% of anti-centromere antibody negative patients were without liver failure. CONCLUSIONS: ANAs in general, and anti-centromere antibodies in particular, are associated with liver failure in PBC. PBC patients with ANAs may be candidates for treatment with experimental therapies to prolong the interval between diagnosis and liver failure. ANA-negative patients, who appear to have a relatively benign clinical course, should perhaps be treated with ursodeoxycholic acid alone.

Antibodies, Antinuclear↗
PubMed2004

A randomized phase II trial of amifostine for head and neck irradiation in lymphoma.

Acute and long-term oral complications occur in patients receiving mantle radiation therapy or irradiation to the head and neck region for Hodgkin's disease or non-Hodgkin's lymphoma. While considerable data are available on the effect of radiation therapy on the oral function and quality of life of patients with squamous cell carcinoma of the head and neck, such information is lacking for similarly irradiated lymphoma patients. In this article we discuss the rationale and study design of an ongoing, randomized phase II study evaluating the role of amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) as a radiation protectant in patients receiving head and neck irradiation for lymphoma. Further investigation in this lymphoma population is needed to improve our understanding of the extent of the problem and its impact on patients' daily living and functioning. Importantly, fine-tuning the treatment and management approaches to minimize morbidity while maximizing the survival and quality of life of patients are crucial next steps.

Adult↗
PubMed2004

FDG-PET is superior to gallium scintigraphy in staging and more sensitive in the follow-up of patients with de novo Hodgkin lymphoma: a blinded comparison.

Accurate staging of Hodgkin lymphoma (HD) allows for minimization of therapy and reduction of long-term toxicities. The present study prospectively compares FDG-PET with gallium/SPECT scintigraphy at time of diagnosis and in follow-up of 36 patients with HD. Prior to therapy, whole body FDG-PET and gallium/SPECT were performed. Follow-up scans were obtained after 3 cycles of chemotherapy (n = 22), and at the end of chemotherapy (n = 32). Two nuclear medicine physicians independently interpreted scans in blinded and random order and a consensus was obtained. Baseline scans revealed a greater number of supradiaphragmatic disease sites detected by PET, and 5 patients had splenic involvement on PET not noted by gallium (P = 0.05); 3 patients were upstaged on PET. Midway through therapy, 5 patients had positive PET (4 of whom relapsed), and 3 had positive gallium (1 relapsed). At conclusion of chemotherapy, 8 patients had a positive PET (4 relapsed) and 3 had a positive gallium (2 relapsed). In conclusion, diagnostic PET and gallium are largely concordant, with the exception of unique detection of splenic disease by PET. However, more patients have persistently positive PET at the end of chemotherapy compared with gallium (P = 0.04), although only half of these patients have relapsed.

Adolescent↗
PubMed2004

Autologous bone marrow transplantation for marginal zone non-Hodgkin's lymphoma.

The marginal zone non-Hodgkin's lymphomas are a recently defined group of related low-grade B cell malignancies whose natural history is heterogeneous. The optimal therapy is often unclear, particularly for the subset of patients with disseminated disease that behaves aggressively. We have retrospectively analyzed the outcomes of 11 patients with chemosensitive but disseminated marginal zone lymphomas who underwent uniform conditioning with cyclophosphamide and total body irradiation followed by bone marrow transplantation (BMT) with anti-B cell monoclonal antibody-purged autologous bone marrow between January 1994 and September 1999. All patients had stage IV disease and received multiple chemotherapy regimens prior to autologous BMT. Only 36% were in complete remission at the time of bone marrow harvest, and 36% had overt bone marrow infiltration at that time. Two treatment-related deaths occurred between 100 days and 6 months. Three patients relapsed and died of disease. One patient developed and died of myelodysplasia. Five patients remain in continuous complete remission at a median follow-up of 52 months (45%). The median progression-free survival for these patients was 56 months, with median overall survival 58 months. The only significant predictor of disease-free and overall survival was age at the time of transplant; no patient under 45 at the time of transplant has relapsed or died of any cause (P = 0.003). Outcomes of autologous BMT in patients with disseminated marginal zone NHL are similar to those in follicular NHL, and suggest that certain patients may experience prolonged disease-free survival.

Adult↗
PubMed2004

Outdoor/Indoor/Personal ozone exposures of children in Nashville, Tennessee.

An ozone (O3) exposure study was conducted in Nashville, TN, using passive O3 samplers to measure six weekly outdoor, indoor, and personal O3 exposure estimates for a group of 10- to 12-yr-old elementary school children. Thirty-six children from two Nashville area communities (Inglewood and Hendersonville) participated in the O3 sampling program, and 99 children provided additional time-activity information by telephone interview. By design, this study coincided with the 1994 Nashville/Middle Tennessee Ozone Study conducted by the Southern Oxidants Study, which provided enhanced continuous ambient O3 monitoring across the Nashville area. Passive sampling estimated weekly average outdoor O3 concentrations from 0.011 to 0.O30 ppm in the urban Inglewood community and from 0.015 to 0.042 ppm in suburban Hendersonville. The maximum 1- and 8-hr ambient concentrations encountered at the Hendersonville continuous monitor exceeded the levels of the 1- and 8-hr metrics for the O3 National Ambient Air Quality Standard. Weekly average personal O3 exposures ranged from 0.0013 to 0.0064 ppm (7-31% of outdoor levels). Personal O3 exposures reflected the proportional amount of time spent in indoor and outdoor environments. Air-conditioned homes displayed very low indoor O3 concentrations, and homes using open windows and fans for ventilation displayed much higher concentrations.

Air Pollutants↗
PubMed2004

Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk.

To assess whether differences in genetic susceptibility to oxidative stress modify asbestos-related lung cancer risk (caused by lung inflammation, free radical production), we examined possible interactions between manganese superoxide dismutase (MnSOD) genotypes and asbestos in a hospital-based case-control study of 811 white lung cancer cases and 957 friend/spouse controls. Cumulative lifetime asbestos exposure score (AES) was calculated from self-reported duration and intensity of occupational and nonoccupational exposures. A total of 13.5% of cases and 10% of controls had "high" AES (determined by a priori cut point). The homozygous variant MnSOD genotype was associated with increased lung cancer risk among individuals with zero or "low" AES (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.52-3.01) and no association (OR = 1.00; 95% CI = 0.36-2.73) among the "high" AES group. We observed no statistically significant interaction between MnSOD genotype and asbestos exposure for lung cancer risk.

Adolescent↗
PubMed2004

Stable expression of small interfering RNA sensitizes TEL-PDGFbetaR to inhibition with imatinib or rapamycin.

Small molecule inhibitors, such as imatinib, are effective therapies for tyrosine kinase fusions BCR-ABL-TEL-PDGFbetaR-mediated human leukemias, but resistance may develop. The unique fusion junctions of these molecules are attractive candidates for molecularly targeted therapeutic intervention using RNA interference (RNAi), which is mediated by small interfering RNA (siRNA). We developed a retroviral system for stable expression of siRNA directed to the unique fusion junction sequence of TEL-PDGFbetaR in transformed hematopoietic cells. Stable expression of the siRNA resulted in approximately 90% inhibition of TEL-PDGFbetaR expression and its downstream effectors, including PI3K and mammalian target of rapamycin (mTOR). Expression of TEL-PDGFbetaR-specific siRNA (TPsiRNA) significantly attenuated the proliferation of TEL-PDGFbetaR-transformed Ba/F3 cells or disease latency and penetrance in mice induced by intravenous injection of these Ba/F3 cells. Although a 90% reduction in TEL-PDGFbetaR expression was insufficient to induce cell death, stable siRNA expression sensitized transformed cells to the PDGFbetaR inhibitor imatinib or to the mTOR inhibitor rapamycin. TPsiRNA also inhibited an imatinib-resistant TEL-PDGFbetaR mutant, and the inhibition was enhanced by siRNA in combination with PKC412, another PDGFbetaR inhibitor. Although siRNA delivery in vivo is a challenging problem, stable expression of siRNA, which targets oncogenic fusion genes, may potentiate the effects of conventional therapy for hematologic malignancies.

Animals↗
PubMed2003

A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group.

The optimal induction for older adults with acute myeloid leukemia (AML) is unknown. Several anthracyclines have been proposed, but the data remain equivocal. Additionally, few prospective trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted. Three hundred and sixty-two older adults with previously untreated AML were randomized to either daunorubicin, idarubicin or mitoxantrone with a standard dose of cytarabine as induction therapy. In addition, 245 patients were also randomized to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia. No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming. However, the complete remission rate for the first 113 analyzable patients, who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did, was significantly higher (50% versus 38%; P =.03). None of the anthracyclines is associated with improved outcome in older adults. Priming with hematopoietic growth factor did not improve response when compared with placebo. Furthermore, delaying induction therapy in older adults may lead to a lower complete remission rate.

Aged↗
PubMed2003

Gemcitabine added to doxorubicin, bleomycin, and vinblastine for the treatment of de novo Hodgkin disease: unacceptable acute pulmonary toxicity.

BACKGROUND: Gemcitabine is an effective treatment for recurrent Hodgkin disease (HD), with relatively minimal associated toxicity. The authors conducted a trial substituting this drug for dacarbazine in the standard regimen to form ABVG (doxorubicin, bleomycin, vinblastine, gemcitabine) for patients with newly diagnosed, high-risk HD. METHODS: Twelve patients (median age, 34 years) with advanced-stage de novo HD were enrolled. Standard doses of doxorubicin, bleomycin, and vinblastine were given for six cycles. Cohorts of three patients were enrolled and the dose of gemcitabine was escalated to identify the maximally tolerated dose in this combination. RESULTS: The maximally tolerated dose of gemcitabine was determined to be 800 mg/m(2) in this combination. Five patients developed clinically significant pulmonary toxicity. Three required hospitalization during the final two cycles of treatment. Pneumonitis could not be predicted with serial diffusion capacity for carbon monoxide (DECO) evaluations, and reversed after discontinuation of bleomycin in three patients and steroid therapy in two patients. All 12 patients are alive to date, and 4 patients have experienced disease progression. CONCLUSIONS: The bleomycin/gemcitabine combination should not be pursued for de novo HD due to significant pulmonary toxicity.

Adult↗
PubMed2003

Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma.

PURPOSE: Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) by retroviral-mediated gene transfer generates potent antitumor immunity in patients with metastatic melanoma. Further clinical development of this immunization scheme requires simplification of vaccine manufacture. We conducted a phase I clinical trial testing the biologic activity of vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer. PATIENTS AND METHODS: Excised metastases were processed to single cells, transduced with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1 x 10(6), 4 x 10(6), or 1 x 10(7) tumor cells, depending on overall yield, and were injected intradermally and subcutaneously at weekly and biweekly intervals. RESULTS: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 745 ng/106 cells/24 hours. Toxicities were restricted to grade 1 to 2 local skin reactions. Eight patients were withdrawn early because of rapid disease progression. Vaccination elicited dense dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates at injection sites in 19 of 26 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransduced tumor cells in 17 of 25 patients. Metastatic lesions that were resected after vaccination showed brisk or focal T-lymphocyte and plasma cell infiltrates with tumor necrosis in 10 of 16 patients. One complete, one partial, and one mixed response were noted. Ten patients (29%) are alive, with a minimum follow-up of 36 months; four of these patients have no evidence of disease. CONCLUSION: Vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma.

Adenoviridae↗
PubMed2003

The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma.

Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL. Like cHLs, MLBCLs also had high levels of expression of the interleukin-13 (IL-13) receptor and downstream effectors of IL-13 signaling (Janus kinase-2 [JAK2] and signal transducer and activator of transcription-1 [STAT1]), tumor necrosis factor (TNF) family members, and TNF receptor-associated factor-1 (TRAF1). Increased expression of STAT1 and TRAF1 in MLBCL was confirmed by immunohistochemistry. Given the TRAF1 expression and known link to nuclear factor-kappa B (NF- kappa B), MLBCLs were also evaluated for nuclear translocation of c-REL protein. In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-kappa B pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway.

Active Transport, Cell Nucleus↗
PubMed2003

Expression of bcl-2 protein is associated with shorter survival in nonsmall cell lung carcinoma.

BACKGROUND: The aim of this study was to assess the relationship between the expression of the 27-kilodalton (kD) bcl-2 protein and survival among nonsmall cell lung carcinoma (NSCLC) patients. METHODS: Paired tissue samples of histologically confirmed tumor and uninvolved lung of 91 randomly selected NSCLC patients were used in this study. The expression of 27-kD bcl-2 proteins in uninvolved lung and tumor tissue specimens was analyzed using Western blot analysis. Overall survival was estimated using the Kaplan-Meier method. The relation between patient survival and expression of the 27-kD bcl-2 protein in uninvolved lung, tumor, and in uninvolved lung and/or tumor tissue specimens was assessed using log-rank tests and Cox proportional hazards multiple regression. RESULTS: The 27-kD bcl-2 protein was expressed in 54% of the uninvolved lung tissue specimens, in 53% of the tumor tissue specimens, and in 70% of the uninvolved lung and/or tumor tissue specimens. When NSCLC patient survival was considered with respect to the expression of the 27-kD bcl-2 protein, a statistically significant shorter survival was observed for patients whose tissue samples expressed the 27-kD bcl-2 protein in the uninvolved lung and in the uninvolved lung and/or tumor (log-rank test, P = 0.008 and P = 0.001, respectively). Cox proportional hazards multiple regression models also showed statistically significant associations between shorter survival and positive 27-kD protein expression in the uninvolved lung (hazard ratio of 2.27; P = 0.05) and in the uninvolved lung and/or tumor (hazard ratio of 5.58, P = 0.008) after controlling for tumor size, stage, the type of surgery received, smoking status, age, and cell type. CONCLUSIONS: In the current study, patients with nonsmall cell lung carcinoma with positive expression of the 27-kD protein bcl-2, either in the uninvolved lung or in uninvolved lung and/or tumor, were found to have significantly poorer postresection survival.

Aged↗
PubMed2003

Hodgkin's disease in elderly patients (> or =60): clinical outcome and treatment strategies.

PURPOSE: Older age is an adverse prognostic factor for survival for patients with Hodgkin's disease. This study assessed the outcome of elderly patients (>or=60 years) with Hodgkin's disease treated with curative intent in an attempt to identify the optimal treatment strategies for this group of patients. METHODS AND MATERIALS: Eighty-six patients, 60-93 years old at the time of diagnosis, were treated for Hodgkin's disease with radical intent between 1969 and 1995. All patients underwent radiographic staging of the chest, abdomen, and pelvis, and 17 patients underwent staging laparotomy. Fifty-two patients had early-stage disease (Stage IA-IIA) and 34 had Stage IIB-IV Hodgkin's disease. The median follow-up time was 75 months (range 24-267) for surviving patients. RESULTS: The 10-year actuarial freedom from treatment failure (FFTF) rate for all patients was 62%. The 10-year FFTF rate for patients with Stage IA-IIA and Stage IIB-IV disease was 71% and 49%, respectively (p = 0.03). Patients with early-stage disease treated with chemoradiotherapy had a lower crude rate of treatment failure (20%) than patients treated with either chemotherapy alone (33%) or radiotherapy alone (46%). However, no statistically significant difference was found between the treatment groups in terms of actuarial FFTF or overall survival. The 5- and 10-year overall survival rate (all causes) for all patients was 48% and 30%, respectively. The 10-year survival rate for patients with Stage IA-IIA and Stage IIB-IV disease was 31% and 26%, respectively (p = 0.07). On multiple regression analysis, including age, treatment, and stage in the Cox regression model with respect to overall survival, age was a marginally significant factor (p = 0.08). For FFTF, age was not a significant factor in the model (p = 0.11). We analyzed the subsequent outcome of patients who developed a first recurrence after initial treatment; the 5-year survival rate was only 20% after recurrence of Hodgkin's disease. Initial treatment was reasonably well tolerated. CONCLUSION: Although more patients died of other causes than Hodgkin's disease, the recurrence of Hodgkin's disease had a significant impact on survival. Thus, we favor the use of chemoradiotherapy in early-stage patients >60 years to minimize the risk of relapse.

Age Factors↗
PubMed2003

Association between self-reported environmental tobacco smoke exposure and lung cancer: modification by GSTP1 polymorphism.

Environmental Tobacco Smoke (ETS) exposure has been associated with lung cancer risk. ETS is composed of emissions from cigarette smoke and contains a higher concentration of tobacco smoke carcinogens than mainstream smoke. Polymorphisms in genes that metabolize tobacco smoke carcinogens have been studied as effect modifiers of the association between active smoking and lung cancer risk. GSTP1 is a polymorphic gene that encodes for GST pi, a detoxification enzyme and has a high expression in the lung. We investigated the association between ETS and lung cancer risk and the modification of this association by the GSTP1 polymorphism. Using a case-control design, individuals were genotyped for GSTP1 using PCR-RFLP techniques. All analyses were carried out using multiple logistic regression. The association between ETS exposure and lung cancer risk was evaluated in different strata based on smoking habits to evaluate the consistency of results. The effect of the GSTP1 polymorphisms on lung cancer risk was evaluated by considering the joint effect of having both an ETS exposure and the GSTP1 GG genotype compared to the absence of ETS exposure and the GSTP1 AA genotype as a reference group as well as doing stratified analysis by genotype. ETS exposure was associated consistently with higher lung cancer risk in all the strata considered. The adjusted odds ratios (AOR) evaluating the association between ETS and lung cancer risk for the different strata were: nonsmokers (Cases/Controls 66/413; AOR = 1.38; 95% CI = 0.78-2.43), ex-smokers (Cases/Controls 560/527; AOR = 1.66; 95% CI = 1.22-2.25), current smokers (Cases/Controls 415/219; AOR = 1.56; 95% CI = 1.00-2.41). The AORs for ex-smokers and light smoking subgroups were: ex-smokers who quit for 19 years or more (Cases/Controls 144/244; AOR = 2.64; 95% CI = 1.55-4.50), ex-smokers who quit for 10-19 years (Cases/Controls 141/128; AOR = 1.16; 95% CI = 0.66-2.04), ex-smokers who quit for 10 years or less (Cases/Controls 247/122; AOR = 1.45; 95% CI = 0.83-2.55) and participants who had <15 packyears and nonsmokers combined (Cases/Controls 143/640; AOR = 1.52; 95% CI = 1.02-2.28). Among those with the GSTP1 GG genotype the ETS-lung cancer risk association was greater than those with the GSTP1 AA genotype: nonsmokers (GSTP1 GG AOR = 7.84; 95% CI = 0.80-76.68; GSTP1 AA AOR = 1.15; 95% CI = 0.46-2.90), ex-smokers (GSTP1 GG AOR = 2.32; 95% CI = 0.90-5.96; GSTP1 AA AOR = 2.15; 95% CI = 1.34-3.44), current smokers (GSTP1 GG AOR = 1.75; 95% CI = 0.42-7.32; GSTP1 AA AOR = 1.32; 95% CI = 0.67-2.58) and participants who had <15 packyears and nonsmokers (GSTP1 GG AOR = 1.93; 95% CI = 0.54-6.97; GSTP1 AA AOR = 1.58; 95% CI = 0.83-3.01). We found that ETS exposure is associated with higher lung cancer risk. Furthermore, the presence of the GSTP1 GG genotype appears to enhance the magnitude of the association between ETS exposure and lung cancer. Larger studies will be needed to confirm these preliminary findings.

Adenocarcinoma↗
PubMed2003

Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma.

PURPOSE: We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial. PATIENTS AND METHODS: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals. RESULTS: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed. CONCLUSION: Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.

Adult↗
PubMed2003

Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193).

PURPOSE: Between February 1993 and September 1995, 739 patients with metastatic breast cancer were entered on an Intergroup trial (E1193) comparing doxorubicin (60 mg/m(2)), paclitaxel (175 mg/m(2)/24 h), and the combination of doxorubicin and paclitaxel (AT, 50 mg/m(2) and 150 mg/m(2)/24 h, plus granulocyte colony-stimulating factor 5 mg/kg) as first-line therapy. Patients receiving single-agent doxorubicin or paclitaxel were crossed over to the other agent at time of progression. PATIENTS AND METHODS: Patients were well balanced for on-study characteristics. RESULTS: Responses (complete response and partial response) were seen in 36% of doxorubicin, 34% of paclitaxel, and 47% of AT patients (P =.84 for doxorubicin v paclitaxel, P =.007 for v AT, P =.004 for paclitaxel v AT). Median time to treatment failure (TTF) is 5.8, 6.0, and 8.0 months for doxorubicin, paclitaxel, and AT, respectively (P =.68 for doxorubicin v paclitaxel, P =.003 for doxorubicin v AT, P =.009 for paclitaxel v AT). Median survivals are 18.9 months for patients taking doxorubicin, 22.2 months for patients taking paclitaxel, and 22.0 months for patients taking AT (P = not significant). Responses were seen in 20% of patients crossing from doxorubicin --> paclitaxel and 22% of patients crossing from paclitaxel --> doxorubicin (P = not significant). Changes in global quality-of-life measurements from on-study to week 16 were similar in all three groups. CONCLUSION: (1) doxorubicin and paclitaxel, in the doses used here, have equivalent activity; (2) the combination of AT results in superior overall response rates and time to TTF; and (3) despite these results, combination therapy with AT did not improve either survival or quality of life compared to sequential single-agent therapy.

Adult↗
PubMed2003

Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.

BACKGROUND: Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru. METHODS: We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes. RESULTS: The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83). CONCLUSIONS: Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes.

Adult↗