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Dive into the research topics where Donald W. Northfelt is active.

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Featured researches published by Donald W. Northfelt.


The New England Journal of Medicine | 1997

Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection

Lawrence D. Kaplan; David J. Straus; Marcia A. Testa; Jamie H. Von Roenn; Bruce J. Dezube; Timothy P. Cooley; Brian Herndier; Donald W. Northfelt; Jenny Huang; Anil Tulpule; Alexandra M. Levine

BACKGROUND Reduced doses of cytotoxic chemotherapy or standard-dose therapy plus a myeloid colony-stimulating factor decreases hematologic toxicity and its complications in patients with non-Hodgkins lymphoma associated with infection with the human immunodeficiency virus (HIV). However, the effect of reducing the doses of cytotoxic chemotherapeutic agents on clinical outcome is not known. METHODS We randomly assigned 198 HIV-seropositive patients with previously untreated, aggressive non-Hodgkins lymphoma to receive standard-dose therapy with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) along with granulocyte-macrophage colony-stimulating factor (GM-CSF; n=94) or reduced-dose m-BACOD with GM-CSF administered only as indicated (n=98). RESULTS A complete response was achieved in 39 of the 94 assessable patients assigned to low-dose therapy (41 percent) and in 42 of the 81 assessable patients assigned to standard-dose therapy (52 percent, P= 0.56). There were no significant differences in overall or disease-free survival; median survival times were 35 weeks for patients receiving low-dose therapy and 31 weeks for those receiving standard-dose therapy (risk ratio for death in the standard-dose group=1.17; 95 percent confidence interval, 0.84 to 1.63; P=0.25). Toxic effects of chemotherapy rated grade 3 or higher occurred in 66 of 94 patients assigned to standard-dose therapy (70 percent) and 50 of 98 patients assigned to low-dose treatment (51 percent, P=0.008). Hematologic toxicity accounted for the difference. CONCLUSIONS As compared with treatment with standard doses of cytotoxic chemotherapy (m-BACOD), reduced doses caused significantly fewer hematologic toxic effects yet had similar efficacy in patients with HIV-related lymphoma. Dose-modified chemotherapy should be considered for most HIV-infected patients with lymphoma.


The Journal of Clinical Pharmacology | 1996

Doxorubicin Encapsulated in Liposomes Containing Surface‐Bound Polyethylene Glycol: Pharmacokinetics, Tumor Localization, and Safety in Patients with AIDS‐Related Kaposi's Sarcoma

Donald W. Northfelt; Francis J. Martin; Paul A. Volberding; Julie Russell; Mary S. Newman; Michael Amantea; Lawrence D. Kaplan

A study of the plasma pharmacokinetics, tumor localization, and safety of a single dose of doxorubicin encapsulated in liposomes containing surface‐bound polyethylene glycol (PEG‐liposomal doxorubicin) was conducted in patients with Kaposis sarcoma (KS) as a manifestation of acquired immune deficiency syndrome (AIDS). Eighteen patients with AIDS‐KS diagnosed by examination of biopsy specimens were randomly assigned to receive either standard doxorubicin or PEG‐liposomal doxorubicin. Consecutive participants were entered at three dose levels (10, 20, and 40 mg/m2) in ascending fashion. Clearance of PEG‐liposomal doxorubicin was 0.034 L/h/m2 to 0.108 L/h/m2, volume of distribution (Vd) was 2.2 L/m2 to 4.4 L/m2, and half‐lives (t1/2) of the initial decline in the plasma concentration—time curve and of the terminal decline were 3.77 hours and 41.3 hours, respectively. Seventy‐two hours after administration, doxorubicin levels observed in lesions of patients receiving PEG‐liposomal doxorubicin were 5.2 to 11.4 times greater than those found in patients given comparable doses of standard doxorubicin. PEG‐liposomal doxorubicin and standard doxorubicin were roughly equipotent in producing toxicity. Encapsulation in liposomes containing surface‐bound PEG significantly limits the distribution and elimination of doxorubicin, results in greater accumulation of the drug in KS lesions 72 hours after dosing than does standard doxorubicin, and may improve drug efficacy and therapeutic index in the treatment of AIDS‐KS.


Journal of Clinical Oncology | 1991

Clinical and virologic effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma: results of a randomized trial.

Lawrence D. Kaplan; James O. Kahn; Suzanne M. Crowe; Donald W. Northfelt; Padraic Neville; Howard Grossberg; Donald I. Abrams; Julie Tracey; John Mills; Paul A. Volberding

Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkins lymphoma (NHL) receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) or no additional therapy. Recombinant rGM-CSF (at a dose of 10-20 micrograms/kg/d) was given on days 1 to 10 (early rGM-CSF) to the first five patients, but was changed to days 4 to 13 (delayed rGM-CSF) of each chemotherapy cycle in subsequent patients. Compared with the control group (N = 10), the delayed rGM-CSF group (N = 11) had higher mean nadirs of the absolute neutrophil count (0.36 v 0.89 x 10(9)/L; P = .009), shorter mean durations of neutropenia (4.9 v 1.3 days; P = .02), fewer chemotherapy cycles complicated by neutropenia and fever (67% v 27%; P = .001), fewer days hospitalized for fever and neutropenia (4.9 v 1.8; P = .004), fewer reductions in chemotherapy dosages, and less frequent delays in chemotherapy administration. No significant differences were observed between patients in the control group and those in the early rGM-CSF group (N = 5). Median levels of serum HIV-1 p24 antigen decreased to 18% and 17% of baseline values in control (N = 4) and rGM-CSF groups (N = 6), respectively, 1 week following administration of the first cycle of chemotherapy. In the third week after chemotherapy, median antigen levels remained below baseline in the control group, but rose to 243% of baseline values in the rGM-CSF group (P = .01), suggesting stimulation of HIV replication. The effect of this change in HIV activity on clinical outcome of treated patients could not be determined, and therefore the clinical significance of this finding remains unclear. Complete response rates of 67%, 70%, and 60% were observed in the control, delayed rGM-CSF, and early rGM-CSF groups, respectively, with corresponding survival times of 9.0, 11.4, and 8.0 months.


The New England Journal of Medicine | 2016

Adaptive Randomization of Veliparib–Carboplatin Treatment in Breast Cancer

Hope S. Rugo; Olufunmilayo I. Olopade; Angela DeMichele; Christina Yau; Laura J. van 't Veer; Meredith Buxton; Michael Hogarth; Nola M. Hylton; Melissa Paoloni; Jane Perlmutter; W. Fraser Symmans; Douglas Yee; A. Jo Chien; Anne M. Wallace; Henry G. Kaplan; Judy C. Boughey; Tufia C. Haddad; Kathy S. Albain; Minetta C. Liu; Claudine Isaacs; Qamar J. Khan; Julie E. Lang; Rebecca K. Viscusi; Lajos Pusztai; Stacy L. Moulder; Stephen Y. Chui; Kathleen A. Kemmer; Anthony Elias; Kirsten K. Edmiston; David M. Euhus

BACKGROUND The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. METHODS In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. RESULTS With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. CONCLUSIONS The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).


Annals of Internal Medicine | 1993

Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection

Ann C. Collier; Robert W. Coombs; Margaret A. Fischl; Paul R. Skolnik; Donald W. Northfelt; Paul Boutin; Carol J. Hooper; Lawrence D. Kaplan; Paul A. Volberding; L. Gray Davis; Denis R. Henrard; Stephen Weller; Lawrence Corey

Zidovudine (AZT, Retrovir) delays progression of human immunodeficiency virus type 1 (HIV-1) infection and prolongs survival in persons with advanced HIV-1 disease [1-5]. However, with prolonged therapy, clinical disease progresses, CD4+ cell counts decrease, and variants of HIV-1 occur that have decreased in vitro susceptibility to zidovudine [6-12]. Didanosine (Videx), another nucleoside analogue that inhibits the reverse transcriptase of HIV-1, increases CD4+ cell counts and delays progression of HIV-1 disease among patients who previously received zidovudine therapy [13-16]. The combination of zidovudine and didanosine has additive to synergistic inhibitory activity against HIV-1 in vitro [17, 18] and is being used clinically, because both agents are licensed and available. We did a clinical trial to characterize the safety and efficacy of a range of doses using combination zidovudine and didanosine therapy compared with zidovudine therapy alone. We found that this combination therapy is well tolerated and is associated with enhanced in vivo activity as shown by higher and more prolonged increases of CD4+ cell counts, with more frequent decreases in plasma HIV-1 RNA titers, and with more stable hematologic measurements than zidovudine therapy alone. Table 1. Pretreatment Characteristics of Patients in the Six Treatment Groups Methods Patients Between February 1990 and August 1991, 69 patients were enrolled in the study: 30 at University of Washington, 14 at University of Miami, 14 at New England Medical Center and Tufts University, and 11 at University of California, San Francisco. Patients had HIV-1 infection, CD4+ cell counts fewer than 400/mm3, fewer than 121 days of previous zidovudine therapy (Retrovir; Burroughs Wellcome Company, Research Triangle Park, North Carolina), and no previous didanosine therapy (Videx; Bristol Laboratories, Princeton, New Jersey). Patients also had granulocyte counts of 1200 cells/mm3 or more, hemoglobin levels greater than 90 g/L, platelet counts greater than 90 000/mm3, creatinine levels less than 1.5 times the upper limit of normal, and aspartate aminotransferase levels less than 5 times the upper limit of normal. Patients were excluded if they had visceral or progressive Kaposi sarcoma; more than four stools per day for 4 weeks; opportunistic infections requiring maintenance therapy; a history of pancreatitis, seizures, peripheral neuropathy, or zidovudine or didanosine intolerance; were pregnant or nursing; were taking experimental medications; or required chronic acyclovir therapy. Study Design The study was an open-label, partially randomized study of five different combination regimens of zidovudine and didanosine and one dosage regimen of zidovudine alone (Figure 1). Zidovudine was given as capsules three times per day. Didanosine was given twice daily as sachets containing a citrate/phosphate buffer with a neutralizing capacity of 30 to 40 mEq/dose. Because of initial concerns about the safety of this combination, enrollment was required in the lower dose groups (groups 1, 2, and 3) before enrollment in groups 4 and 5. In March 1991, after enrollment was completed in groups 1 to 5, the protocol was modified to enroll consecutively identified eligible patients in the zidovudine-alone regimen (group 6), to permit a comparison with standard therapy. Because standard zidovudine therapy in the United States at the time this trial was done was 500 to 600 mg daily, the groups that included zidovudine at 600 mg daily (groups 3, 5, and 6) were planned to have larger enrollment than the other groups. Treatment duration was 24 weeks. Patients were replaced if they discontinued treatment permanently before week six for reasons other than toxicity. Figure 1. Outline of the study design. Patient Evaluation The study protocol was approved by institutional review boards of participating institutions, and patients gave written informed consent. Patients had a standardized clinical and laboratory evaluation at enrollment and had weekly follow-up visits for 4 weeks and then every 2 weeks. Symptoms and signs were assessed at each visit and were graded as absent or within normal limits, or as mild, moderate, severe, or life-threatening severity. Patients at the University of Washington in groups 3 (n = 9) and 5 (n = 6) had blood samples collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours for pharmacokinetic assays, after a single 200-mg zidovudine dose, 2 days before starting study drugs, and after a single 167- or 250-mg didanosine dose on the day before starting combination therapy. In addition, 26 patients in groups 3 and 5 had plasma collected on a similar schedule during weeks 2 (n = 26) and 12 (n = 23). Doses of study drugs were modified if patients had moderate peripheral neuropathy or certain severe toxicities. Study drugs were permanently discontinued for severe or life-threatening toxicities. Laboratory Measurements CD4+ and CD8+ cells from peripheral blood were enumerated using monoclonal antibodies and flow cytometry [19]. Sera from each patient, frozen at 30C, were assayed simultaneously for HIV-1 p24 antigen by an enzyme-linked immunosorbent assay (Abbott Laboratories, North Chicago, Illinois). A positive result for HIV-1 was defined as 12 pg/mL using an HIV-1 p24 antigen reference standard supplied by the AIDS Clinical Trials Group Virology Reference Laboratory. Sera from patients enrolled at the University of Washington were also assayed for immune-complex dissociated-HIV p24 antigen (Abbott Laboratories). Plasma from patients enrolled at the University of Washington, stored at 70C, was assayed for HIV-1 RNA by a semiquantitative polymerase chain reaction technique, as previously described [20]. All assays were done in duplicate on coded samples, and the semiquantitative assessment of the polymerase chain reaction-signal strength was graded using scanning densitometry without knowledge of any clinical data or treatment group. Zidovudine concentrations in plasma were determined by radioimmunoassay [21]. Plasma didanosine concentrations were analyzed by high-performance liquid chromatography [22]. Data Analysis Comparisons among groups were made using chi-square analysis or the Fisher exact test for discrete variables and using the Wilcoxon Mann-Whitney test and Kruskal-Wallis test among three or more groups for continuous variables. All P values were two-tailed. To evaluate the effect of therapy for sequentially monitored variables, area-under-the-curve (AUC) analyses were done based on absolute change from pretreatment or time-averaged absolute change from pretreatment values. The baseline CD4+ cell count was an average of two pretreatment counts for each patient. The AUC for CD4+ cell counts was calculated by multiplying the average CD4+ cell count between two successive time points by the time elapsed between those time points, summing these areas for the study period, and dividing the result by the duration of the study period. This AUC was strongly related to the pretreatment CD4+ cell count. Analysis of covariance, adjusting for the initial CD4+ cell count, was used to examine the relation between the treatment group and the AUC. Residuals from the model were analyzed, and no pattern was discernible, suggesting the model was appropriate. Area-under-the-curve analysis, based on absolute CD4+ cell changes from pretreatment values, was used to compare these areas across groups using nonparametric statistics. The proportion of patients with an increase in absolute CD4+ cells of 50 and 100 cells/mm3, on two consecutive measurements above the pretreatment value, was evaluated using contingency tables. The duration of response was defined as the time to two consecutive counts at or below baseline and was analyzed using Kaplan-Meier survival techniques. Pharmacokinetic parameter estimates were calculated by standard methods and included the peak concentration (Cmax), the time to peak concentration (Tmax), the elimination half-life (t1/2), the AUC, and the apparent oral clearance. The evaluation of a pharmacokinetic drug interaction between zidovudine and didanosine was done by paired t-test analysis of parameter estimates obtained for those patients in groups 3 and 5 who received single doses of zidovudine alone (day 2) and didanosine alone (day 1) followed by coadministration of both compounds with pharmacokinetic evaluations in weeks 2 and 12. Parameter estimates were considered statistically different for P values less than 0.05. Results Study Patients Sixty-seven (97%) patients were men; 61 (88%) were white, 2 (3%) were black, and 6 (9%) were of other races. The mean age (SD) was 34 6 years. Fifty-four (78%) were homosexual or bisexual men, 8 (12%) were homosexual or bisexual men who also used injection drugs, 2 (3%) were injection drug users, 3 (4%) had heterosexually acquired HIV-1, 1 (1%) had hemophilia, and 1 (1%) had unknown risk behavior for HIV. Thirty-eight (55%) patients were asymptomatic, 22 (32%) had constitutional symptoms, and 9 (13%) had the acquired immunodeficiency syndrome (AIDS). The median pretreatment CD4+ cell count was 259 cells/mm3, and the median Karnofsky performance score was 100. No statistical differences were seen in demographic, clinical, or laboratory characteristics among the six dosing groups, except for the expected difference in frequency of detectable HIV-1 p24 antigen (Table 1). The median HIV-1 p24 antigen level for patients in group 1 was 140 pg/mL (range, 17 to 282 pg/mL). Thirty-one patients had taken previous zidovudine therapy; the mean duration of therapy (SD) was 65 days ( 36 days). Fifty-eight (84%) patients completed 24 weeks of study treatment and 11 (16%) discontinued study treatment, 5 before week 6. Pretreatment characteristics of patients who discontinued treatment were similar to those who completed therapy. The reasons for study medication discontinuation were toxicity (3 patients), administrative reasons (4


Journal of Acquired Immune Deficiency Syndromes | 1998

Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS

Jacob Lalezari; Gary N. Holland; Kramer F; G. F. Mckinley; Carol A. Kemper; David V. Ives; R. Nelson; W. D. Hardy; Baruch D. Kuppermann; Donald W. Northfelt; Youle M; Margaret Johnson; Richard Alan Lewis; David V. Weinberg; Gary L. Simon; R. A. Wolitz; A. E. Ruby; Stagg Rj; Jaffe Hs

To assess the effect of intravenous cidofovir on delaying progression of previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a randomized, controlled comparison of two maintenance dose levels of cidofovir. One hundred and fifty patients with AIDS and CMV retinitis that had progressed or was persistently active despite treatment with ganciclovir, foscarnet, or both were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week. Concomitant probenecid and intravenous hydration were administered with each cidofovir dose. Retinitis progression was assessed in the first 100 patients by bilateral, full-field retinal photographs read at a central reading center by an ophthalmologist masked to treatment assignment. Incidence of side effects, changes in visual acuity, and mortality were also assessed. Median time to retinitis progression as assessed by retinal photography was not reached (95% confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group, and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose-dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%) were the most common adverse events thought to be related to cidofovir. Reversible probenecid reactions including constitutional symptoms and nausea occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying progression of CMV retinitis that had previously progressed using other anti-CMV therapies.


Clinical Cancer Research | 2013

Phase II Study of Bevacizumab in Combination with Sorafenib in Recurrent Glioblastoma (N0776): A North Central Cancer Treatment Group Trial

Evanthia Galanis; S. Keith Anderson; Jackie M. Lafky; Joon H. Uhm; Caterina Giannini; Shaji Kumar; Teresa K. Kimlinger; Donald W. Northfelt; Patrick J. Flynn; Kurt A. Jaeckle; Timothy J. Kaufmann; Jan C. Buckner

Purpose: We hypothesized that vertical blockade of VEGF signaling by combining bevacizumab with sorafenib in patients with recurrent glioblastoma would result in a synergistic therapeutic effect. We also investigated whether VEGF, VEGFR2 and hypoxia-inducible factor-1α single-nucleotide polymorphisms (SNP), circulating biomarkers of angiogenesis, and MRI markers such as apparent diffusion coefficient (ADC) are correlated with treatment efficacy and/or toxicity. Experimental Design: Patients received bevacizumab (5 mg/kg every 2 weeks) with sorafenib (200 mg twice a day, weekly, days 1–5; group A). Due to toxicity, the starting sorafenib dose was subsequently modified to 200 mg every day (group B). Results: Fifty-four patients were enrolled: 19 patients in group A and 35 in group B. Objective response rate was 18.5% with median duration of 6.7 months (range 0.5–24.1 months). Six-month progression-free survival (PFS6) was 20.4% (11/54), and median overall survival (OS) was 5.6 months [95% confidence interval (CI), 4.7–8.2]; outcome was similar between the two dose groups. We identified SNPs in the VEGF and VEGFR2 promoter regions, which were associated with PFS6 (P < 0.022). Among molecular markers of angiogenesis, a higher log2 baseline level of stromal cell–derived factor-1 was associated with PFS6 success (P = 0.04). Circulating endothelial cells decreased during treatment with subsequent increase at disease progression (P = 0.022). Imaging analysis showed a trend associating ADC-L with poor outcome. Conclusions: The bevacizumab/sorafenib combination did not improve outcome of patients with recurrent glioblastoma versus historic bevacizumab-treated controls. Biologic markers of response and resistance to bevacizumab in gliomas were identified which merit prospective validation. Clin Cancer Res; 19(17); 4816–23. ©2013 AACR.


Journal of Clinical Oncology | 2013

Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial

Sandra M. Swain; Gong Tang; Charles E. Geyer; Priya Rastogi; James N. Atkins; Paul P. Donnellan; Louis Fehrenbacher; Catherine A. Azar; André Robidoux; Jonathan Polikoff; Adam Brufsky; David D. Biggs; Edward A. Levine; John L. Zapas; Louise Provencher; Donald W. Northfelt; Soonmyung Paik; Joseph P. Costantino; Eleftherios P. Mamounas; Norman Wolmark

PURPOSE Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. PATIENTS AND METHODS We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigators discretion. RESULTS There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). CONCLUSION Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.


Mayo Clinic Proceedings | 2008

Trastuzumab-induced cardiotoxicity: heart failure at the crossroads.

Partho P. Sengupta; Donald W. Northfelt; Federico Gentile; José Zamorano; Bijoy K. Khandheria

Trastuzumab, a drug targeting human epidermal growth factor receptor 2, improves survival rate in women with metastatic breast cancer. Symptomatic heart failure, a serious adverse effect of trastuzumab, occurs in 1% to 4% of patients treated with the antibody, whereas left ventricular ejection fraction declines substantially in 10% of patients. The prevalence of cardiotoxic effects of trastuzumab appears to increase with exposure to anthracyclines. Serial assessment of left ventricular function with 2-dimensional echocardiography or radionuclide ventriculography is the most practical means of monitoring cardiotoxicity. Patients who develop cardiotoxicity while receiving trastuzumab therapy generally improve once use of the agent is discontinued.


Annals of Internal Medicine | 1988

The Acquired Immunodeficiency Syndrome Is a Primary Care Disease

Donald W. Northfelt; Rodney A. Hayward; Martin F. Shapiro

Excerpt A crisis is looming for patients with the acquired immunodeficiency syndrome (AIDS): The small number of subspecialists and other interested physicians now caring for most patients with AID...

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