bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of 6% Miltefosine Solution, a Topical Chemotherapy in Cutaneous Metastases From Breast Cancer
Authors: Leonard R. , Hardy J. , van Tienhoven G. , Houston S. , Simmonds P. , David M. , Mansi J. 
Published: February 2017

PURPOSE: To compare 6% miltefosine solution (Miltex; Asta Medica, Frankfurt, Germany), a new topical cytostatic drug, with placebo as palliative treatment for cutaneous metastases from breast cancer. PATIENTS AND METHODS: In a double-blind, placebo-controlled, multicenter phase III study, a total of 52 patients with inoperable progressive skin lesions from histologically or cytologically confirmed breast cancer, not manageable by radiotherapy or systemic treatment, with superficial or flat skin lesions (estimated depth of invasion ≤ 1 cm) were randomized to receive either 6% miltefosine solution or placebo. The solution was applied at the dose of 2 drops/10 cm2, once daily during the first week and twice daily thereafter until treatment failure. RESULTS: Treatment groups were well balanced for patient characteristics at study entry except for a small difference in age. Time to treatment failure (TTF), the primary parameter of this study, showed miltefosine solution to be significantly superior to placebo (P = .007); the median TTF in the miltefosine solution group was nearly three times longer than that in the placebo group (56 days v 21 days). The rate of response based on intention to treat patients was 33.3% for miltefosine solution compared with 3.7% for placebo (P = .006). Cutaneous reactions were seen mainly in the miltefosine group, with the type and frequency similar to those observed in previous studies. CONCLUSION: 6% Miltefosine solution is confirmed as an effective palliative treatment option for cutaneous metastases from breast cancer. Skin reactions, when present, are well tolerated and only occasionally require cessation of treatment.
Phase II Trial of the Anti-GD2Monoclonal Antibody 3F8 and Granulocyte-Macrophage Colony-Stimulating Factor for Neuroblastoma
Authors: Kushner Brian H. , Kramer Kim , Cheung Nai-Kong V. 
Published: February 2017

PURPOSE: To describe oncolytic effects of treatment with anti-GD2monoclonal antibody 3F8 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with neuroblastoma (NB).PATIENTS AND METHODS: Patients were eligible for 3F8/GM-CSF if intensive therapy had not eradicated potentially lethal NB. One cycle consisted of GM-CSF (subcutaneous bolus) on days 1 through 5, 11, and 12, and GM-CSF (2-hour intravenous [IV] infusion) followed after a 1-hour interval by 3F8 (1.5-hour IV infusion) on days 6 through 10 and 13 through 17. GM-CSF was dosed at 250 μg/m2/d on days 1 through 7 and at 500 μg/m2/d on days 8 through 17. 3F8 was dosed at 10 mg/m2/d (100 mg/m2/cycle). 3F8 was given with an opiate and an antihistamine. Patients without progressive disease (PD) or elevated human antimouse antibody titers could be treated again beginning 3 weeks after completion of a cycle.RESULTS: Among 19 patients treated for NB resistant to induction therapy, 12 of 15 had complete remission (CR) of bone marrow (BM) disease, and three others who had less than partial responses achieved prolonged progression-free survival (one remains on study at 21+ months, two had PD at 12 and 17 months). Among patients treated for recurrent NB resistant to retrieval therapy, five of 10 had CR in BM. The 15 patients treated for PD fared poorly, although two had scintigraphic findings suggestive of a short-term response. Side effects were limited to readily manageable pain and, less commonly, rash of short duration; hence, patients were treated as outpatients.CONCLUSION: 3F8/GM-CSF is well tolerated and shows promise for treatment of minimal residual NB in BM.
Phase III Randomized Intergroup Trial of Subtotal Lymphoid Irradiation Versus Doxorubicin, Vinblastine, and Subtotal Lymphoid Irradiation for Stage IA to IIA Hodgkin’s Disease
Authors: Press Oliver W. , LeBlanc Michael , Lichter Allen S. , Grogan Thomas M. , Unger Joseph M. , Wasserman Todd H. , Gaynor Ellen R. , Peterson Bruce A. , Miller Thomas P. , Fisher Richard I. 
Published: February 2017

PURPOSE: The management of early-stage Hodgkin’s disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin’s disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin’s disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P < .001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.
Activity of Oral Fludarabine Phosphate in Previously Treated Chronic Lymphocytic Leukemia
Authors: Boogaerts M. A. , Van Hoof A. , Catovsky D. , Kovacs M. , Montillo M. , Zinzani P. L. , Binet J. L. , Feremans W. , Marcus R. , Bosch F. , Verhoef G. , Klein M. 
Published: February 2017

PURPOSE: A prospective, multicenter, open-label phase II clinical trial was conducted to assess the efficacy and safety of oral fludarabine phosphate. Reference to an historical group of patients treated with the intravenous (IV) formulation allowed the investigators to compare the two formulations. PATIENTS AND METHODS: Efficacy was assessed using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) and National Cancer Institute (NCI) criteria for complete remission (CR), partial remission (PR), stable disease, or disease progression. Safety monitoring included World Health Organization (WHO) toxicity grading for all adverse events. RESULTS: Seventy-eight (96.3%) of 81 recruited patients with previously treated B-cell chronic lymphocytic leukemia (CLL) received 10-mg tablets of fludarabine phosphate to a dose of 40 mg/m2/d for 5 days, repeated every 4 weeks, for a total of six to eight cycles. According to IWCLL criteria, the overall remission rate was 46.2% (CR, 20.5%; PR, 25.6%). The comparative figures using NCI criteria were 51.3% (CR, 17.9%; PR, 33.3%). Overall, 30 incidents of severe adverse events were reported for 22 patients. WHO grade 3 or grade 4 hematologic toxicities included granulocytopenia (53.8%), leukocytopenia (28.2%), thrombocytopenia (25.6%), and anemia (24.4%). Gastrointestinal adverse events were more common with the oral formulation than previously reported with IV fludarabine phosphate. However, these events were generally mild to moderate. CONCLUSION: This study demonstrates that oral fludarabine phosphate has similar clinical efficacy to the IV formulation and a safety profile that is both predictable and essentially similar to that of the IV formulation.
Lack of Adherence With the Analgesic Regimen: A Significant Barrier to Effective Cancer Pain Management
Authors: Miaskowski Christine , Dodd Marylin J. , West Claudia , Paul Steven M. , Tripathy Debu , Koo Peter , Schumacher Karen 
Published: February 2017

PURPOSE: To evaluate oncology outpatients’ level of adherence to their analgesic regimen during a 5-week period.PATIENTS AND METHODS: A random sample of 65 adult oncology outpatients with a Karnofsky performance status score of ≥ 50, an average pain intensity score of ≥ 2.5, and radiographic evidence of bone metastasis were recruited for this longitudinal study from seven outpatient settings. On a daily basis, patients rated their level of pain intensity and recorded pain medication intake. Adherence rates for opioid analgesics prescribed on an around-the-clock (ATC) and on an as-needed (PRN) basis were calculated on a weekly basis.RESULTS: Overall adherence rates for ATC opioid analgesics ranged from 84.5% to 90.8% and, for PRN analgesics, from 22.2% to 26.6%. No significant differences over time were found in either of these adherence rates.CONCLUSION: One factor that seems to contribute to ineffective cancer pain management is poor adherence to the analgesic regimen.
CD8+ T Cells in Cutaneous T-Cell Lymphoma: Expression of Cytotoxic Proteins, Fas Ligand, and Killing Inhibitory Receptors and Their Relationship With Clinical Behavior
Authors: Vermeer Maarten H. , van Doorn Remco , Dukers Danny , Bekkenk Marcel W. , Meijer Chris J.L.M. , Willemze Rein 
Published: February 2017

PURPOSE: We investigated the number, phenotype, and prognostic significance of CD8+ T cells in patients with mycosis fungoides (MF) and CD30− primary cutaneous large T-cell lymphoma (PCLTCL).PATIENTS AND METHODS: Immunohistochemical stainings for CD8, granzyme B (GrB), T cell–restricted intracellular antigen (TIA-1), Fas ligand (FasL), and killer-cell inhibitory receptors (KIRs; CD95, CD158a, and CD158b) were performed on 83 first-diagnostic biopsy samples obtained from patients with plaque-stage MF (n = 42), tumor-stage MF (n = 20), and CD30− PCLTCL (n = 21).RESULTS: Serial sections and double-staining experiments showed that the large majority of CD8+ T cells in MF and CD30− PCLTCL expressed TIA-1 and FasL, whereas only a minority expressed GrB, which suggested that these CD8+ T cells were partly activated cytotoxic T lymphocytes (CTLs). These CD8+ CTLs never or rarely expressed KIRs. This phenotype was a constant feature of CD8+ CTLs and did not alter with disease progression. In contrast, the median percentage of CD8+ CTLs in plaque-stage MF (22%), tumor-stage MF (7%), and CD30− PCLTCL (3%) differed significantly (P < .0001) and was associated with a significant decrease in 5-year survival. Also within the group of tumor-stage MF, a significant relation between CD8+ CTLs and survival was found. Multivariate analysis in the total group of MF demonstrated that both skin stage and percentage of CD8+ CTLs were independent parameters of survival.CONCLUSION: Our results demonstrated that partly activated CD8+ CTLs were present in CTCL and that high proportions of these cells correlated with a better prognosis. This suggested that these CD8+ CTLs could play an important role in the antitumor response in these conditions.
Long-Term Results of Combined-Modality Therapy for Locally Advanced Breast Cancer With Ipsilateral Supraclavicular Metastases: The University of Texas M.D. Anderson Cancer Center Experience
Authors: Brito Rogelio A. , Valero Vicente , Buzdar Aman U. , Booser Daniel J. , Ames Frederick , Strom Eric , Ross Merrick , Theriault Richard L. , Frye Debra , Kau Shu-Wan , Asmar Lina , McNeese Marsha , Singletary S. Eva , Hortobagyi Gabriel N. 
Published: February 2017

PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy. PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor–positive tumors received tamoxifen for 5 years. RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred. CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.
CD4+ T-Cell Immune Response to Large B-Cell Non-Hodgkin’s Lymphoma Predicts Patient Outcome
Authors: Ansell Stephen M. , Stenson Mary , Habermann Thomas M. , Jelinek Diane F. , Witzig Thomas E. 
Published: February 2017

PURPOSE: Previous studies in patients with non-Hodgkin’s lymphoma (NHL) and other malignancies have suggested that the presence of host infiltrates in the tumors of these patients may predict a better outcome. This study was undertaken to determine the prognostic importance of the presence of T cells in the biopsy specimens of patients with B-cell NHL.PATIENTS AND METHODS: Seventy-two patients with diffuse large B-cell NHL were prospectively evaluated at a single institution between 1987 and 1994. The percentage of CD3+, CD3+/HLA-DR+, CD4+, CD8+, and natural killer cells was determined by flow cytometry in the pretreatment diagnostic biopsy specimen and correlated with patient outcome.RESULTS: An increase in the percentage CD4+ T cells in the pretreatment tumor biopsies significantly correlated with patient outcome. The percent of CD4+ T cells was also highly correlated with CD3+/HLA-DR+, CD45RO+, and low l-selectin (CD62L) expression, indicating that the CD4+ T cells are activated memory T-helper cells. Those patients with increased numbers of CD4+ T cells, compared with other patients, had a significantly longer 5-year failure-free survival (72% v 43%, respectively; P = .04), as well as a significantly longer 5-year overall survival (65% v 38%, respectively; P = .05). When evaluated in a multivariate model, the International Prognostic Index and more than 20% infiltrating CD4+ T cells in the pretreatment biopsy were significant independent predictors of relapse-free and overall survival.CONCLUSION: The presence of increased numbers of activated CD4+ cells in the area of B-cell diffuse large-cell NHL predicts a better prognosis. This finding provides a strong rationale for the investigation of cellular immunotherapy in B-cell NHL.
Results of a Prospective Trial of Mantle Irradiation Alone for Selected Patients With Early-Stage Hodgkin’s Disease
Authors: Backstrand Kendall H. , Ng Andrea K. , Takvorian Ronald W. , Jones Ellen L. , Fisher David C. , Molnar-Griffin Beverly J. , Silver Barbara , Tarbell Nancy J. , Mauch Peter M. 
Published: February 2017

PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin’s disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin’s disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had ≥ 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin’s disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P = .04). Significant differences in FFTF were not seen by histology (P = .26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P = .25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin’s disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.
Concurrent Paclitaxel and Radiation in the Treatment of Locally Advanced Head and Neck Cancer
Authors: Sunwoo John B. , Herscher Laurie L. , Kroog Glenn S. , Thomas Giovana R. , Ondrey Frank G. , Duffey Dianne C. , Solomon Beth I. , Boss Carol , Albert Paul S. , McCullugh Linda , Rudy Susan , Muir Chris , Zhai Suoping , Figg William D. , Cook John A. , Mitchell James B. , Van Waes Carter 
Published: February 2017

PURPOSE: To determine the feasibility of an organ preservation regimen consisting of infusional paclitaxel administered concurrently with radiotherapy to patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Thirty-three previously untreated patients with stage III or IV tumors were enrolled onto the study. Paclitaxel was administered as a 120-hour continuous infusion every 3 weeks during the course of radiation therapy. Sixteen patients received a paclitaxel dose of 105 mg/m2, and 17 patients received 120 mg/m2. Radiation was delivered in a standard format at 1.8 Gy/d to a total dose of 70.2 to 72 Gy. RESULTS: Three months after therapy, a 76% complete response (CR) at the primary site and a 70% overall CR was achieved. At 36 months, locoregional control was 55.7%, overall survival was 57.8%, and disease-free survival was 51.1%. The median survival duration for all 33 patients was greater than 50 months at the time of this report. Local toxicities including mucositis, dysphagia, and skin reactions were severe but tolerable. All patients retained functional speech, and all but four patients were swallowing food 3 months after treatment. Steady-state plasma concentrations for paclitaxel were not achieved during a 120-hour infusion, suggesting a nonlinear process. Tumor volume quantified by pretreatment computerized tomography imaging was associated with likelihood of response and survival. CONCLUSION: Paclitaxel administered as a 120-hour continuous infusion in combination with radiotherapy is a feasible and promising treatment for patients with advanced HNSCC.
Phase I Trial of the Combination of Irinotecan, Paclitaxel, and Carboplatin in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Socinski Mark A. , Sandler Alan B. , Miller Langdon L. , Locker Paula K. , Hanover Cristy K. , Elfring Gary L. , Israel Valerie K. , Pirotta Nicoletta , Natale Ronald B. 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose, toxicities, and dose suitable for phase II/III trials of irinotecan (CPT-11) combined with paclitaxel and carboplatin in patients with advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were enrolled to this multicenter, phase I study. The initial regimen was paclitaxel 225 mg/m2/3 h, followed by carboplatin area under the curve (AUC) 6 over 30 minutes on day 1, and CPT-11 starting at 40 mg/m2 over 90 minutes, days 1 and 8, every 3 weeks. Dose-limiting toxicity occurred in three of seven patients. The regimen was amended, with doses reduced to paclitaxel 175 mg/m2/3 h, carboplatin AUC 5 and CPT-11 at 40 mg/m2, all on day 1 every 3 weeks. Dose escalation of CPT-11 proceeded to 80 mg/m2 then 125 mg/m2 before dose-limiting toxicities were experienced. Subsequent patients received an intermediate CPT-11 dose of 100 mg/m2. RESULTS: Thirty-three patients were enrolled; 32 patients were assessable for safety, and 31 were assessable for tumor response. The primary first-cycle dose-limiting toxicities were neutropenia and diarrhea. The most common grade 3/4 toxicity observed during all cycles was neutropenia (16 patients [50%], with six [19%] developing neutropenic fever). Objective tumor response was observed in 39% (12/31, 95% confidence interval, 22% to 58%). The median time to tumor progression was 6.8 months, median survival 11.0 months, and 1-year survival probability 0.46. CONCLUSION: CPT-11 100 mg/m2, paclitaxel 175 mg/m2, and carboplatin AUC 5 given every 3 weeks can be safely administered in patients with advanced NSCLC. Neutropenia and diarrhea are the dose-limiting toxicities. The combination shows appreciable activity, and survival data are favorable.
Phase I Study of Topotecan Plus Cranial Radiation for Glioblastoma Multiforme: Results of Radiation Therapy Oncology Group Trial 9507
Authors: Fisher Barbara J. , Scott C. , Macdonald D. R. , Coughlin C. , Curran W. J. 
Published: February 2017

PURPOSE: A phase I trial was conducted by the Radiation Therapy Oncology Group (RTOG) to determine the maximum-tolerated dose of topotecan that could be safely combined with standard cranial radiation for glioblastoma multiforme. A secondary objective was to document the acute and late toxicities of this combination of chemotherapy and radiation. PATIENTS AND METHODS: Forty-seven patients with histologically confirmed glioblastoma multiforme were entered onto this phase I trial. Three cycles of topotecan were administered at 21-day intervals commencing at day 1 of cranial radiotherapy (60 Gy/30 fractions). Each cycle consisted of daily 30-minute intravenous (IV) infusions for 5 days. The dose of topotecan was escalated in three-dose increments from 0.5 mg/m2/d to 1.0 mg/m2/d to 1.5 mg/m2/d in different patient groups. RESULTS: The majority of patients were over age 50. Three dose levels of topotecan were tested. Fifteen patients accrued to level 1 (topotecan dose 0.5 mg/m2/d). No grade 4 toxicities were seen. Sixteen patients accrued to level 2 (topotecan dose 1.0 mg/m2/d), five of whom had brief episodes of grade 4 neutropenia. Seventeen patients accrued to level 3 (1.5 mg/m2/d). Six of these patients had brief episodes of grade 4 neutropenia and four developed grade 3 thrombocytopenia. No serious nonhematologic or late toxicities were seen. Median survival for all patients was 9.7 months. There was no apparent difference in survival by topotecan dose schedule. CONCLUSION: Toxicity was acceptable at an IV topotecan dose of 1.5 mg/m2/d administered daily for 5 days every 21 days for three cycles. A phase II trial has been performed using this dose of topotecan.