bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Axillary Lymph Node Dissection Indicated for Early-Stage Breast Cancer? A Decision Analysis
Authors: Parmigiani Giovanni , Berry Donald A. , Winer Eric P. , Tebaldi Claudia , Iglehart J. Dirk , Prosnitz Leonard R. 
Published: February 2017

PURPOSE: Axillary lymph node dissection (ALND) has been a standard procedure in the management of breast cancer. In a patient with a clinically negative axilla, ALND is performed primarily for staging purposes, to guide adjuvant treatment. Recently, the routine use of ALND has been questioned because the results of the procedure may not change the choice of adjuvant systemic therapy and/or the survival benefit of a change in adjuvant therapy would be small. We constructed a decision model to quantify the benefits of ALND for patients eligible for breast-conserving therapy. METHODS: Patients were grouped by age, tumor size, and estrogen receptor (ER) status. The model uses the Oxford overviews and three combined Cancer and Leukemia Group B studies. We assumed that patients who did not undergo ALND received axillary radiation therapy and that the two procedures are equally effective. All chemotherapy combinations were assumed to be equally efficacious. RESULTS: The largest benefits from ALND are seen in ER-positive women with small primary tumors who might not be candidates for adjuvant chemotherapy if their lymph nodes test negative. Virtually no benefit results in ER-negative women, almost all of whom would receive adjuvant chemotherapy. When adjusted for quality of life (QOL), ALND may have an overall negative impact. In general, the benefits of ALND increase with the expected severity of adjuvant therapy on QOL. CONCLUSION: Our model quantifies the benefits of ALND and assists decision making by patients and physicians. The results suggest that the routine use of ALND in breast cancer patients should be reassessed and may not be necessary in many patients.
Effect of Tamoxifen on Sexual Functioning in Patients With Breast Cancer
Authors: Mortimer Joanne E. , Boucher Leslie , Baty Jack , Knapp Diana L. , Ryan Elizabeth , Rowland Julia H. 
Published: February 2017

PURPOSE: To define the incidence of sexual dysfunction in a population of women with breast cancer treated with tamoxifen. PATIENTS AND METHODS: Breast cancer patients with a performance status of 0 to 2 who had been treated with tamoxifen for 2 to 24 months completed the following measures: the Center for Epidemiologic Studies–Depression Scale, the Sexual History Form, and the Breast Cancer Prevention Trial Symptom Checklist. Forty-nine of the participants underwent gynecologic examinations with vaginal smears for determination of estrogen effect. RESULTS: Fifty-seven women were entered onto the trial. Sexual desire, arousal, and ability to achieve orgasm were comparable to norms established in participants in the Tamoxifen Prevention Trial (National Surgical Adjuvant Breast and Bowel Project P-01). Pain, burning, or discomfort with intercourse was reported in 54% of patients and did not correlate with age, surgical treatment of the primary cancer, or chemotherapy. Estrogen effect was seen on the vaginal smears of 34 of 49 participants and was more common in older patients (P = .054). The presence of estrogen effect correlated with negative reactions during sex (P = .02) and vaginal dryness or tightness (P = .046). CONCLUSION: Women treated with tamoxifen in the adjuvant setting experienced symptoms of sexual dysfunction. The individual contributions of chemotherapy and tamoxifen to sexual dysfunction warrant prospective study.
Randomized Trial of Low-Dose Chemotherapy Added to Tamoxifen in Patients With Receptor-Positive and Lymph Node–Positive Breast Cancer
Authors: Jakesz R. , Hausmaninger H. , Haider K. , Kubista E. , Samonigg H. , Gnant M. , Manfreda D. , Tschurtschenthaler G. , Kolb R. , Stierer M. , Fridrik M. , Mlineritsch B. , Steindorfer P. , Mittlböck M. , Steger G. 
Published: February 2017

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor–positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m2 and vincristine 1 mg/m2 on day 1; cyclophosphamide 300 mg/m2; methotrexate 25 mg/m2; and fluorouracil 600 mg/m2 on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.
Single-Agent Monoclonal Antibody Efficacy in Bulky Non-Hodgkin's Lymphoma: Results of a Phase II Trial of Rituximab
Authors: Davis T. A. , White C. A. , Grillo-López A. J. , Velásquez W. S. , Link B. , Maloney D. G. , Dillman R. O. , Williams M. E. , Mohrbacher A. , Weaver R. , Dowden S. , Levy R. 
Published: February 2017

PURPOSE: A phase II trial was performed to evaluate the safety and efficacy of rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with bulky (> 10-cm lesion) relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (NHL).PATIENTS AND METHODS: Thirty-one patients received intravenous infusions of rituximab 375 mg/m2weekly for four doses. All patients had at least one prior therapy (median, three; range, one to 13) and had progressive disease at study entry. Patients were a median of 4 years from diagnosis.RESULTS: No patient had treatment discontinued because of an adverse event. No patient developed human antichimeric antibody. The overall response rate in 28 assessable patients was 43% with a median time to progression of 8.1 months (range, 4.5 to 18.6+ months) and median duration of response of 5.9 months (range, 2.8 to 12.1+ months). The average decrease in lesion size in patients who achieved a partial response was 76%, and patients with stable disease had a decrease in average lesion size of 26%. Median serum antibody concentration was higher in responders compared with nonresponders, and a negative correlation was shown between antibody concentration and tumor bulk at baseline.CONCLUSION: Rituximab single-agent outpatient therapy is safe and shows significant clinical activity in patients with bulky relapsed or refractory low-grade or follicular B-cell NHL.
Outcomes of High-Dose Chemotherapy and Autologous Stem-Cell Transplantation in Stage IIIB Inflammatory Breast Cancer
Authors: Adkins D. , Brown R. , Trinkaus K. , Maziarz R. , Luedke S. , Freytes C. , Needles B. , Wienski D. , Fracasso P. , Pluard T. , Moriconi W. , Ryan T. , Hoelzer K. , Safdar S. , Rearden T. , Rodriguez G. , Khoury H. , Vij R. , DiPersio J. 
Published: February 2017

PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)–positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P = .04) and receipt of tamoxifen (P = .06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59.6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies.
Phase I Clinical and Pharmacologic Study of 13-cis-Retinoic Acid, Interferon Alfa, and Paclitaxel in Patients With Prostate Cancer and Other Advanced Malignancies
Authors: DiPaola R. S. , Rafi M. M. , Vyas V. , Toppmeyer D. , Rubin E. , Patel J. , Goodin S. , Medina M. , Medina P. , Zamek R. , Zhang C. , White E. , Gupta E. , Hait W. N. 
Published: February 2017

PURPOSE: Recent studies demonstrate that retinoids decrease expression of the anti-apoptotic protein bcl-2, enhance the effect of chemotherapy, and act synergistically with interferon alfa (IFNα) to inhibit tumor cell growth in vitro. A phase I trial of 13-cis-retinoic acid (CRA), IFNα, and paclitaxel (TAX) was conducted to determine the toxicity and recommended phase II dose of this combination. Pharmacodynamic studies were performed to determine whether CRA and IFNα could modulate bcl-2 expression in vitro and in patients. PATIENTS AND METHODS: Twenty-two patients with prostate cancer or other advanced malignancies were treated with CRA/IFNα and escalating doses of TAX. The effect of CRA/IFNα on TAX pharmacokinetics was analyzed in both patients and human liver microsomes. The effect of CRA/IFNα on bcl-2 expression was assessed in vitro and in peripheral-blood mononuclear cells (PBMCs) by immunoblotting. RESULTS: CRA 1 mg/kg on days 1 to 4, IFNα 6 MU/m2 subcutaneously on days 1 to 4, and TAX 175 mg/m2 onday 3 was well tolerated. Pharmacokinetic studies demonstrated that CRA/IFNα caused a 33% decrease in TAX clearance and a 23% decrease in the area under the concentration-time curve values of the TAX metabolite 6-alfa-hydroxytaxol (6-HT). CRA alone reduced conversion of TAX to 6-HT by 41% in human liver microsomes. CRA/IFNα decreased bcl-2 expression in vitro and in PBMCs. CONCLUSION: CRA/IFNα and TAX is a well-tolerated regimen. CRA/IFNα increases TAX area under the concentration-time curve through an inhibitory effect of CRA on the metabolism of TAX to 6-HT. CRA/IFNα can modulate bcl-2 expression in vitro and demonstrates similar biologic activity in patients. Further studies will determine the activity of CRA/IFNα/TAX and validate the assessment of bcl-2 in PBMCs as a marker of tumor response.
Analysis of Factors That Correlate With Mucositis in Recipients of Autologous and Allogeneic Stem-Cell Transplants
Authors: Rapoport Aaron P. , Miller Watelet Luc F. , Linder Tammy , Eberly Shirley , Raubertas Richard F. , Lipp Joanna , Duerst Reggie , Abboud Camille N. , Constine Louis , Andrews Jessica , Etter Mary Ann , Spear Linda , Powley Elizabeth , Packman Charles H. , Rowe Jacob M. , Schwertschlag Ullrich , Bedrosian Camille , Liesveld Jane L. 
Published: February 2017

PURPOSE: To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy. PATIENTS AND METHODS: Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea. Potential covariates included patient age, sex, diagnosis, treatment protocol, transplantation type, stem-cell source, and rate of neutrophil recovery. The three selected end points were also examined for correlation with blood infections and transplant-related mortality. RESULTS: A diagnosis of leukemia, use of total body irradiation, allogeneic transplantation, and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support. No factors were associated with diarrhea. Also, moderate to severe oral mucositis (MUCPEAK ≥ 18 on a scale of 8 to 24) was correlated with blood infections and transplant-related mortality: 60% of patients with MUCPEAK ≥ 18 had positive blood cultures versus 30% of patients with MUCPEAK less than 18 (P = .001); 24% of patients with MUCPEAK ≥ 18 died during the transplantation procedure versus 4% of patients with MUCPEAK less than 18 (P = .001). CONCLUSION: Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality, emphasizing the need for corrective strategies. The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinically significant events, including blood infections and treatment-related mortality.
Hydrocortisone With or Without Mitoxantrone in Men With Hormone-Refractory Prostate Cancer: Results of the Cancer and Leukemia Group B 9182 Study
Authors: Kantoff Philip W. , Halabi Susan , Conaway Mark , Picus Joel , Kirshner Jeffrey , Hars Vera , Trump Donald , Winer Eric P. , Vogelzang Nicholas J. 
Published: February 2017

PURPOSE: Approximately 40,000 men die each year of hormone-refractory prostate cancer (HRPC). The results of treatment with chemotherapy have been disappointing to date, with no trials demonstrating a benefit with respect to survival duration. Corticosteroids and mitoxantrone each have been shown to be active agents in this disease. The purpose of this study was to demonstrate an advantage of mitoxantrone and hydrocortisone (M+H) over hydrocortisone alone with respect to survival duration. PATIENTS AND METHODS: Two hundred forty-two patients with HRPC were randomized to receive either M+H or hydrocortisone alone. Patients were monitored for survival, time to disease progression, time to treatment failure, response, and quality-of-life (QOL) parameters. RESULTS: Treatment in both arms was well tolerated. Although there was a delay in time to treatment failure and disease progression in favor of M+H over hydrocortisone alone, there was no difference in overall survival (12.3 months for M+H v 12.6 months for hydrocortisone alone). There was an indication that QOL was better with M+H, in particular with respect to pain control. CONCLUSION: M+H generated more frequent responses and a delay in both time to treatment failure and disease progression compared with hydrocortisone alone. In addition, there was a possible benefit of M+H with respect to pain control over hydrocortisone alone. No improvement in survival was observed. Although M+H could be viewed as a palliative option for patients with HRPC, new drugs and novel strategies are needed to improve survival for this disease.
Phase I Trial to Determine the Safety, Pharmacodynamics, and Pharmacokinetics of RSR13, a Novel Radioenhancer, in Newly Diagnosed Glioblastoma Multiforme
Authors: Kleinberg L. , Grossman S. A. , Piantadosi S. , Pearlman J. , Engelhard H. , Lesser G. , Ruffer J. , Gerber M. 
Published: February 2017

PURPOSE: To determine the safety, pharmacokinetics, and pharmacodynamic effect of 2-[4-(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylproprionic acid (RSR13) 100 mg/kg/d with radiation therapy (RT) for glioblastoma multiforme (GBM). RSR13, a synthetic allosteric modifier of hemoglobin (HgB), is a novel radioenhancing agent that noncovalently binds to HgB, thereby reducing oxygen binding affinity and increasing tissue oxygen release to hypoxic tissues. PATIENTS AND METHODS: In this multi-institutional, dose frequency–seeking trial, 19 adult patients with newly diagnosed GBM received RSR13 100 mg/kg every other day or daily along with cranial RT (60 Gy/30 fractions). RSR13 was given over 1 hour by central venous access with 4 L/min of O2 by nasal cannula, followed by RT within 30 minutes. Pharmacokinetic (PK) and pharmacodynamic (PD) determinations were performed. The PD end point was shift in P50, the oxygen half-saturation pressure of HgB. RESULTS: Grade 3 dose-limiting toxicity occurred innone of the patients with every-other-day dosing and in two of the 10 patients with daily dosing. Grade 2 or greater toxicity occurred in three out of nine and six out of 10, respectively. PK and PD data demonstrate that a substantial PD effect was reliably achieved, that PD effect was related to RBC RSR13 concentration, and that there was no significant drug accumulation even with daily dosing. The mean shift in P50 was 9.24 ± 2.6 mmHg (a 34% increase from baseline), which indicates a substantial increase in tendency toward oxygen unloading. CONCLUSION: Daily RSR13 (100 mg/kg) during cranial RT is well tolerated and achieves the desired PD end point. A phase II trial of daily RSR13 for newly diagnosed malignant glioma is currently accruing patients within the New Approaches to Brain Tumor Therapy Central Nervous System Consortium to determine survival outcome.
Phase I and Pharmacokinetic Study of Temozolomide on a Daily-for-5-Days Schedule in Patients With Advanced Solid Malignancies
Authors: Hammond Lisa A. , Eckardt John R. , Baker Sharyn D. , Eckhardt S. Gail , Dugan Margaret , Forral Kelly , Reidenberg Pascale , Statkevich Paul , Weiss Geoffrey R. , Rinaldi David A. , Von Hoff Daniel D. , Rowinsky Eric K. 
Published: February 2017

PURPOSE: To determine the principal toxicities, characterize the pharmacokinetics (PKs) and pharmacodynamics (PDs) of temozolomide (TMZ) on a daily-for-5-days schedule, and recommend a dose for subsequent disease-directed studies in both minimally pretreated (MP) and heavily pretreated (HP) patients. PATIENTS AND METHODS: Patients received TMZ as a single oral dose daily for 5 consecutive days every 28 days. TMZ doses were escalated from 100 to 150, and 150 to 200 mg/m2/d in separate cohorts of MP and HP patients. PK plasma was sampled on days 1 and 5. TMZ concentrations were analyzed and pertinent PK parameters were related to the principal toxicities of TMZ in PD analyses. RESULTS: Twenty-four patients were treated with 85 courses of TMZ. Thrombocytopenia and neutropenia were the principal dose-limiting toxicities (DLTs) of TMZ on this schedule. The cumulative rate of severe myelosuppressive effects was unacceptably high at TMZ doses exceeding 150 mg/m2/d in both MP and HP patients. TMZ was absorbed rapidly with maximum concentrations achieved in 0.90 hours, on average, and elimination was rapid, with a half-life and systemic clearance rate (ClS/F) averaging 1.8 hours and 115 mL/min/m2, respectively. When clearance was normalized to body-surface area (BSA), interpatient variability in ClS/F was reduced from 20% to 13% on day 1 and from 16% to 10% on day 5. Patients who experienced DLT had significantly higher maximum drug concentration (median 16 v 9.5 μg/mL, P = .0084) and area under the concentration-time curve (median 36 v 23 μg-h/mL, P = .0019) values on day 5. CONCLUSION: Prior myelosuppressive therapy was not a determinant of toxicity. TMZ 150 mg/m2/d administered as a single oral dose daily for 5 days every 4 weeks is well tolerated by MP and HP patients, with higher doses resulting in unacceptably high rates of severe hematologic toxicity. TMZ doses should be individualized according to BSA rather than use of a prespecified oral dose for all individuals. TMZ is an optimal agent to develop in combination with other cytotoxic, biologic, and targeted therapeutics for patients with relevant malignancies.
Outpatient-Based Bone Marrow Transplantation for Hematologic Malignancies: Cost Saving or Cost Shifting?
Authors: Rizzo J. Douglas , Vogelsang Georgia B. , Krumm Sharon , Frink Barbara , Mock Victoria , Bass Eric B. 
Published: February 2017

PURPOSE: To determine whether a shift in care from an inpatient-based to an outpatient-based bone marrow transplantation (BMT) program decreased charges to payers without increasing clinical complications or out-of-pocket costs to patients. PATIENTS AND METHODS: This nonrandomized prospective cohort study compared clinical and economic outcomes for 132 consecutive BMT patients with hematologic malignancies who received either inpatient- or outpatient-based BMT care. RESULTS: Seventeen of 132 BMT patients underwent outpatient-based BMT. Compared with the inpatient-based group, the outpatient-based group had a markedly lower mean number of inpatient hospital days (22 v 47; P < .001) and decreased mean inpatient facility charges ($61,059 less per patient; P < .0001) but had higher mean outpatient facility charges ($49,732 higher; P < .0001). Total professional fees were similar for the groups. The mean total charge to payers was only 7% less ($12,652; P = .21) for outpatient-based BMT than for inpatient-based BMT, but total charge was 34% less for outpatient compared with inpatient BMT ($54,240; P = 0.056) in a subset of patients who had a standard rather than high risk of treatment failure. There was no significant difference between groups in out-of-pocket costs for transportation, lodging, meals, home nursing, household assistance, child care, medication expenses, or unreimbursed medical bills. There also was no significant difference between groups in reported income lost, involuntary unemployment, or months of disability. The two groups had similar rates of major complications, including death, significant acute graft-versus-host disease, and veno-occlusive disease of the liver. CONCLUSION: Increased use of outpatient-based BMT should produce substantial cost savings for payers without adverse effects on patients for those patients who do not have a high risk of treatment failure.