bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation Therapy With Concomitant Hydroxyurea and Fluorouracil in Stage II and III Head and Neck Cancer
Authors: Haraf Daniel J. , Kies Merrill , Rademaker Alfred W. , Stenson Kerstin , Mittal Bharat , Pelzer Harold , Wenig Barry , Witt Mary Ellyn , Sulzen Laura , Weichselbaum Ralph R. , Vokes Everett E. 
Published: February 2017

PURPOSE: In 1986, a multi-institutional phase II trial was begun to study the use of chemotherapy with concomitant radiation in patients with stage II and III head and neck cancer. End points were overall survival, progression-free survival, local/regional control, and toxicity in the setting of organ preservation with concomitant treatment. METHODS: Eligible patients with stage II or III disease received chemotherapy and radiation on a 2-week cycle. Chemotherapy consisted of continuous infusion fluorouracil (5-FU) at 800 mg/m2/d for 5 consecutive days (days 1 to 5) and hydroxyurea (HU) at 1 g orally every 12 hours for 13 doses starting the evening before the start of irradiation. Radiation therapy was given as single 1.8- to 2.0-Gy fractions for 5 consecutive days (days 1 to 5) with chemotherapy. Each 5 days of treatment was followed by a 9-day break (days 6 to 14), during which no additional treatment was given. Treatment cycles were repeated until the completion of the planned radiation dose (six to eight cycles). RESULTS: Between 1989 and 1996, 60 patients were enrolled. All patients were eligible for analysis, with a median follow-up of 52 months for surviving patients and 42 months for all patients. Grade 3 to 4 mucositis occurred in 57% of patients. The 5 year-actuarial overall survival, progression-free survival, and local/regional control were 65%, 82%, and 86%, respectively. Eight patients developed local and/or regional recurrence after treatment. Surgical salvage was possible in three of these patients. Thus, the ultimate 5-year local/regional control was 91%. CONCLUSION: Concomitant radiation and chemotherapy with 5-FU and HU is an effective regimen in patients with stage II and III head and neck cancer. Progression-free survival and local/regional control appear to be superior to expected rates in patients treated with surgery and radiation. Further testing of this regimen in a phase III setting is indicated.
Health-Related Quality of Life 1 Year After Allogeneic or Autologous Stem-Cell Transplantation: A Prospective Study
Authors: Hjermstad Marianne J. , Evensen Stein A. , Kvaløy Stein O. , Fayers Peter M. , Kaasa Stein 
Published: February 2017

PURPOSE: To evaluate health-related quality of life (HRQOL) in adults treated with high-dose chemotherapy followed by allogeneic (SCT) and autologous (ASCT) stem-cell transplantation 1 year after transplantation, using data from concurrent lymphoma patients receiving combination chemotherapy (CT) as a reference. MATERIALS AND METHODS: Forty-one leukemia patients (SCT group), 51 lymphoma patients (ASCT group), and 85 CT patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline and after 1 year. RESULTS: The SCT group (median age, 36 years) had better functioning scores and less symptomatology at baseline compared with the ASCT (median age, 41 years) and CT (median age, 37 years) groups. Statistically significant differences of 10 or more points on the 0 to 100 scales were found for 10 of 15 scales and items (P ≤ .01) between the SCT and ASCT groups. Global quality of life (79 v 58, P < .0001), role function (83 v 65, P = .001), sleep disturbances (6 v 28, P < .0001), and fatigue (25 v 44, P = .0001) deviated most. The differences were 10 or more points for seven of 15 scales and items comparing the SCT and CT groups, with sleep disturbances (6 v 35, P < .0001) and pain (11 v 29, P < .01) deviating most. Differences across groups were smaller after 1 year; cognitive function was the only scale with a statistically significant difference (ASCT 80 v CT 89; P = .002). Patterns of change in HRQOL scores were different between groups during follow-up. A great improvement was found in the ASCT group (P < .01 for emotional and role function, fatigue, appetite, and constipation), whereas no significant changes were observed for the SCT group. CONCLUSION: Prospective studies with extended follow-up periods are necessary to separate a slow recovery process from more permanently reduced HRQOL after transplantation and to examine the late side effects from previous treatment.
Phase I and Pharmacologic Study of the Combination of Paclitaxel, Cisplatin, and Topotecan Administered Intravenously Every 21 Days as First-Line Therapy in Patients With Advanced Ovarian Cancer
Authors: Herben Virginie M.M. , Nannan Panday Vinodh R. , Richel Dick J. , Schellens Jan H.M. , van der Vange Nine , Rosing Hilde , Beusenberg Fred D. , Hearn Solange , Doyle Edward , Beijnen Jos H. , ten Bokkel Huinink Wim W. 
Published: February 2017

PURPOSE: To evaluate the feasibility of administering topotecan in combination with paclitaxel and cisplatin without and with granulocyte colony-stimulating factor (G-CSF) support as first-line chemotherapy in women with incompletely resected stage III and stage IV ovarian carcinoma. PATIENTS AND METHODS: Starting doses were paclitaxel 110 mg/m2 administered over 24 hours (day 1), followed by cisplatin 50 mg/m2 over 3 hours (day 2) and topotecan 0.3 mg/m2/d over 30 minutes for 5 consecutive days (days 2 to 6). Treatment was repeated every 3 weeks. After encountering dose-limiting toxicities (DLTs) without G-CSF support, the maximum-tolerated dose was defined as 5 μg/kg of G-CSF subcutaneously starting on day 6. RESULTS: Twenty-one patients received a total of 116 courses at four different dose levels. The DLT was neutropenia. At the first dose level, all six patients experienced grade 4 myelosuppression. G-CSF support permitted further dose escalation of cisplatin and topotecan. Nonhematologic toxicities, primarily fatigue, nausea/vomiting, and neurosensory neuropathy, were observed but were generally mild. Of 15 patients assessable for response, nine had a complete response, four achieved a partial response, and two had stable disease. CONCLUSION: Neutropenia was the DLT of this combination of paclitaxel, cisplatin, and topotecan. The recommended phase II dose is paclitaxel 110 mg/m2 (day 1), followed by cisplatin 75 mg/m2 (day 2) and topotecan 0.3 mg/m2/d (days 2 to 6) with G-CSF support repeated every 3 weeks.
Age, Sex, and Smoking Are Predictors of Circulating Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor–Binding Protein 3
Authors: Kaklamani Virginia G. , Linos Athena , Kaklamani Evangelia , Markaki Ioanna , Mantzoros Christos 
Published: February 2017

PURPOSE: Insulin-like growth factor (IGF-1) and its major binding protein (IGF-BP3) have recently been implicated in the pathogenesis of several malignancies. However, anthropometric and lifestyle predictors of these hormones have not been elucidated. Here we report the results of a cross-sectional study. SUBJECTS AND METHODS: This cross-sectional study examines the relationship of a series of epidemiologic parameters (age, sex, height, body mass index, smoking, alcohol consumption, and coffee drinking) with IGF-1 and IGF-BP3 in a sample of 130 healthy adults. RESULTS: We observed that serum levels of IGF-1 are higher, whereas levels of IGF-BP3 are lower, in men than in women. In addition, serum levels of IGF-1 are independently and negatively associated with age and positively associated with pack-year history of smoking. Finally, serum levels of IGF-BP3 are independently and negatively associated with the number of cigarettes smoked per day or pack-year history of smoking. CONCLUSION: Age, sex, and smoking are independent predictors of IGF-1 and/or IGF-BP3. The influence of these epidemiologic variables on the pathogenesis of disease states associated with IGF-1 and IGF-BP3 warrants further exploration.
Pamidronate Reduces Skeletal Morbidity in Women With Advanced Breast Cancer and Lytic Bone Lesions: A Randomized, Placebo-Controlled Trial
Authors: Theriault Richard L. , Lipton Allan , Hortobagyi Gabriel N. , Leff Richard , Glück Stefan , Stewart John F. , Costello Sean , Kennedy Ian , Simeone Joseph , Seaman John J. , Knight Robert D. , Mellars Kathleen , Heffernan Maika , Reitsma Dirk J. 
Published: February 2017

PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.
Quantitative Polymerase Chain Reaction for the Detection of Micrometastases in Patients With Breast Cancer
Authors: Slade Martin J. , Smith Brendan M. , Sinnett H. Dudley , Cross Nicholas C.P. , Coombes R. Charles 
Published: February 2017

PURPOSE: Previous reports have indicated that reverse transcriptase polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK-19) may be useful in the management of patients with breast cancer. However, the specificity of this technique is low, principally because of a high rate of false-positive results. To improve the specificity of this assay, we developed a quantitative RT-PCR methodology that enables an estimate to be made of the number of CK-19 transcripts in blood and bone marrow samples. PATIENTS AND METHODS: We examined 45 peripheral-blood samples and 30 bone marrow samples from patients with a variety of nonneoplastic conditions using nested RT-PCR for CK-19. We also examined bone marrow and peripheral-blood samples from 23 patients with primary breast cancer and peripheral-blood samples from 37 patients with metastatic breast cancer. The number of CK-19 transcripts was estimated in positive specimens by competitive PCR and normalized to the number of ABL transcripts as an internal control for the quality and quantity of cDNA. RT-PCR results were compared with the numbers of CK-19–positive cells detected by immunocytochemistry. RESULTS: Analysis of samples from patients without cancer enabled us to define an upper limit for the background ratio of CK-19 to ABL transcripts (1:1,000 for blood samples and 1:1,600 for bone marrow samples). Using these figures as cut-off points, elevated CK-19: ABL ratios were detected in peripheral-blood samples of 20 of 37 (54%) patients with metastatic breast cancer and in bone marrow samples of 14 of 23 (61%) patients with primary breast cancer. Only three of 23 (13%) primary breast cancer peripheral-blood samples and none of the control samples were positive by these criteria. Only two of 23 patients (9%) with primary breast cancer showed immunocytochemically detectable cells in the blood; 10 of 23 (43%) showed immunocytochemically detectable cells in the bone marrow. Of 36 patients with metastatic breast cancer, eight (22%) showed positive events. CONCLUSION: Quantitative RT-PCR for CK-19 detects a percentage of patients with breast cancer and may enable the progression or regression of the disease to be monitored.
Phase I Trial of Escalating Doses of Paclitaxel Plus Doxorubicin and Dexrazoxane in Patients With Advanced Breast Cancer
Authors: Sparano Joseph A. , Speyer James , Gradishar William J. , Liebes Leonard , Sridhara Rajeshwari , Mendoza Sandra , Fry David , Egorin Merrill J. 
Published: February 2017

PURPOSE: To determine the maximum-tolerable dose (MTD) of paclitaxel given as a 3-hour intravenous (IV) infusion that could be used in conjunction with doxorubicin and dexrazoxane, and to determine the effect of dexrazoxane on the pharmacokinetics of paclitaxel and doxorubicin. PATIENTS AND METHODS: Twenty-five patients with advanced breast cancer received dexrazoxane (600 mg/m2 by IV infusion over 15 minutes), followed 15 minutes later by doxorubicin (60 mg/m2 IV), followed 15 minutes later by paclitaxel (150 or 175 mg/m2 by IV infusion over 3 hours) in cohorts of three to six patients using a standard phase I design without (group A) and with (group B) granulocyte colony-stimulating factor (G-CSF). Treatment continued until there was a substantial decrease in the left ventricular ejection fraction (LVEF), congestive heart failure, progressive disease, or physician discretion to discontinue. RESULTS: The MTD of paclitaxel was 150 mg/m2, and adjunctive therapy with G-CSF was required to prevent febrile neutropenia. Dexrazoxane had no significant effect on the pharmacokinetics of paclitaxel or doxorubicin. After a median cumulative doxorubicin dose of 360 mg/m2 (range, 60 to 870 mg/m2), no patient developed congestive heart failure or had a decrease in LVEF below normal. An objective response occurred in all five patients with locally advanced breast cancer and in eight of 20 patients (40%; 95% confidence interval, 19% to 61%) with metastatic breast cancer. CONCLUSION: When combined with doxorubicin (60 mg/m2) and dexrazoxane (600 mg/m2), paclitaxel given as a 3-hour infusion had an MTD of 150 mg/m2, and G-CSF was required to prevent febrile neutropenia. Dexrazoxane had no effect on the pharmacokinetics of paclitaxel or doxorubicin. No patient in this trial had a decrease in the LVEF below normal, compared with about 20% to 50% of patients treated with doxorubicin and paclitaxel without dexrazoxane in other trials.
Multi-Institutional Melanoma Lymphatic Mapping Experience: The Prognostic Value of Sentinel Lymph Node Status in 612 Stage I or II Melanoma Patients
Authors: Gershenwald Jeffrey E. , Thompson William , Mansfield Paul F. , Lee Jeffrey E. , Colome Maria I. , Tseng Chi-hong , Lee J. Jack , Balch Charles M. , Reintgen Douglas S. , Ross Merrick I. 
Published: February 2017

PURPOSE: To compare the effect of pathologic sentinel lymph node (SLN) status with that of other known prognostic factors on recurrence and survival in patients with stage I or II cutaneous melanoma. PATIENTS AND METHODS: We reviewed the records of 612 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between January 1991 and May 1995 to determine the effects of tumor thickness, ulceration, Clark level, location, sex, and SLN pathologic status on disease-free and disease-specific survival. RESULTS: In the 580 patients in whom lymphatic mapping and SLN biopsy were successful, the SLN was positive by conventional histology in 85 patients (15%) but negative in 495 patients (85%). SLN status was the most significant prognostic factor with respect to disease-free and disease-specific survival by univariate and multiple covariate analyses. Although tumor thickness and ulceration influenced survival in SLN-negative patients, they provided no additional prognostic information in SLN-positive patients. CONCLUSION: Lymphatic mapping and SLN biopsy is highly accurate in staging nodal basins at risk for regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy. Furthermore, pathologic status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for recurrence. The information from SLN biopsy is particularly helpful in establishing stratification criteria for future adjuvant trials.
Phase II Study of Phenylacetate in Patients With Recurrent Malignant Glioma: A North American Brain Tumor Consortium Report
Authors: Chang Susan M. , Kuhn John G. , Robins H. Ian , Schold S. Clifford , Spence Alexander M. , Berger Mitchel S. , Mehta Minesh P. , Bozik Michael E. , Pollack Ian , Schiff David , Gilbert Mark , Rankin Cathy , Prados Michael D. 
Published: February 2017

PURPOSE: To determine the response rate, time to treatment failure, and toxicity of phenylacetate in patients with recurrent malignant glioma and to identify plasma concentrations achieved during repeated continuous infusion of this agent. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma were treated with phenylacetate. The schedule consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off). A starting dose of 400 mg/kg total body weight per day of phenylacetate was initially used and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient dose escalations were allowed to a maximum of 450 mg/kg ideal body weight/d. Tumor response was assessed every 8 weeks. The National Cancer Institute common toxicity criteria were used to assess toxicity. Plasma concentrations achieved during the patients' first two 14-day infusions were assessed. RESULTS: Forty-three patients were enrolled between December 1994 and December 1996. Of these, 40 patients were assessable for toxicity and response to therapy. Reversible symptoms of fatigue and somnolence were the primary toxicities, with only mild hematologic toxicity. Thirty (75%) of the 40 patients failed treatment within 2 months, seven (17.5%) had stable disease, and three (7.5%) had a response defined as more than 50% reduction in the tumor. Median time to treatment failure was 2 months. Thirty-five patients have died, with a median survival of 8 months. Pharmacokinetic data for this dose schedule showed no difference in the mean plasma concentrations of phenylacetate between weeks 1 and 2 or between weeks 5 and 6. CONCLUSION: Phenylacetate has little activity at this dose schedule in patients with recurrent malignant glioma. Further studies with this drug would necessitate an evaluation of a different dose schedule.
Phase I and Pharmacologic Study of the Tyrosine Kinase Inhibitor SU101 in Patients With Advanced Solid Tumors
Authors: Eckhardt S. Gail , Rizzo Jinee , Sweeney Kevin R. , Cropp Gillian , Baker Sharyn D. , Kraynak,† Maura A. , Kuhn John G. , Villalona-Calero Miguel A. , Hammond Lisa , Weiss Geoffrey , Thurman Allison , Smith Lon , Drengler Ronald , Eckardt John R. , Moczygemba Judy , Hannah Alison L. , Von Hoff Daniel D. , Rowinsky Eric K. 
Published: February 2017

PURPOSE: To evaluate the clinical feasibility and pharmacologic behavior of the platelet-derived growth factor (PDGF) tyrosine kinase inhibitor SU101, administered on a prolonged, intermittent dosing schedule to patients with advanced solid malignancies. PATIENTS AND METHODS: Twenty-six patients were treated with SU101 doses ranging from 15 to 443 mg/m2 as a 24-hour continuous intravenous (IV) infusion weekly for 4 weeks, repeated every 6 weeks. Pharmacokinetic studies were performed to characterize the disposition of SU101 and its major active metabolite, SU0020. Immunohistochemical staining of PDGF-α and -β receptors was performed on malignant tumor specimens obtained at diagnosis. RESULTS: Twenty-six patients were treated with 52 courses (187 infusions) of SU101. The most common toxicities were mild to moderate nausea, vomiting, and fever. Two patients experienced one episode each of grade 3 neutropenia at the 333 and 443 mg/m2 dose levels. Dose escalation of SU101 above 443 mg/m2/wk was precluded by the total volume of infusate required, 2.5 to 3.0 L. Individual plasma SU101 and SU0020 concentrations were described by a one-compartment model that incorporates both first-order formation and elimination of SU0020. SU101 was rapidly converted to SU0020, which exhibited a long elimination half-life averaging 19 ± 12 days. At the 443 mg/m2/wk dose level, trough plasma SU0020 concentrations during weeks 2 and 4 ranged from 54 to 522 μmol/L. Immunohistochemical studies revealed PDGF-α and -β receptor staining in the majority (15 of 19) of malignant neoplasms. CONCLUSION: SU101 was well tolerated as a 24-hour continuous IV infusion at doses of up to 443 mg/m2/wk for 4 consecutive weeks every 6 weeks. Although further dose escalation was precluded by infusate volume constraints, this SU101 dose schedule resulted in the achievement and maintenance of substantial plasma concentrations of the major metabolite, SU0020, for the entire treatment period.
Multitargeted Antifolate LY231514 as First-Line Chemotherapy for Patients With Advanced Non–Small-Cell Lung Cancer: A Phase II Study
Authors: Rusthoven James J. , Eisenhauer Elizabeth , Butts Charles , Gregg Richard , Dancey Janet , Fisher Bryn , Iglesias Jose 
Published: February 2017

PURPOSE: To evaluate the efficacy and safety of the multitargeted antifolate LY231514 (MTA) in patients receiving initial chemotherapy for unresectable, advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with measurable, advanced NSCLC who had not received previous chemotherapy for advanced disease were considered for this study. Eligible patients who gave written informed consent initially received MTA 600 mg/m2 intravenously (IV) for 10 minutes every 3 weeks. After three patients received treatment at this dose, the dose was reduced to 500 mg/m2 IV at the same infusion time and frequency because of toxicity seen in this study and another Canadian MTA trial in colorectal cancer. Patients received up to four cycles after complete or partial remission or six cycles after stable disease was documented. RESULTS: Thirty-three patients were accrued onto the study. All were assessable for toxicity, and 30 patients were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance status score of 0 or 1, 18 patients (55%) had adenocarcinoma, and nine patients (27%) had squamous cell carcinoma. Twenty-five patients (76%) had stage IV disease, and the remainder had stage IIIB disease at trial entry. Seven patients experienced a confirmed partial response and no complete responses were seen; thus, the overall response rate was 23.3% (95% confidence interval, 9.9% to 42.3%). The median duration of response was 3.1 months (range, 2.3 to 13.5 months) after a median follow-up period of 7.9 months. Four (67%) of six patients with stage IIIB disease and three (12.5%) of 24 with stage IV disease responded to treatment. Four patients (13.3%) experienced febrile neutropenia and 13 (39%) experienced grade 3 or 4 neutropenia, whereas only one patient (3%) developed grade 4 thrombocytopenia. Nonhematologic toxicity was generally mild or moderate, but 39% of patients developed a grade 3 skin rash. Most other toxicities comprised grade 1 or 2 stomatitis, diarrhea, lethargy, and anorexia. Ten patients stopped protocol therapy because of toxicity. CONCLUSION: MTA seems to have clinically meaningful activity as a single agent against advanced NSCLC. Toxicity is generally mild and tolerable. Further study of this agent in combination with cisplatin and other active drugs is warranted in this disease.