bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Evaluation of ISIS 3521, an Antisense Oligodeoxynucleotide to Protein Kinase C-Alpha, in Patients With Advanced Cancer
Authors: Nemunaitis J. , Holmlund J. T. , Kraynak M. , Richards D. , Bruce J. , Ognoskie N. , Kwoh T. J. , Geary R. , Dorr A. , Von Hoff D. , Eckhardt S. G. 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose (MTD) and pharmacologic behavior of ISIS 3521 (ISI 641A), an antisense phosphorothioate oligonucleotide to protein kinase C-alpha. PATIENTS AND METHODS: Thirty-six patients with advanced cancer received 99 cycles of ISIS 3521 (0.15 to 6.0 mg/kg/d) as a 2-hour intravenous infusion administered three times per week for 3 consecutive weeks and repeated every 4 weeks. Plasma and urine sampling was performed during the first week of treatment and subjected to capillary gel electrophoresis to determine full-length antisense oligonucleotide in addition to chain-shortened metabolites. RESULTS: Drug-related toxicities included mild to moderate nausea, vomiting, fever, chills, and fatigue. Hematologic toxicity was limited to thrombocytopenia (grade 1, four patients; grade 2, one patient; grade 3, one patient). There was no relationship between dose, maximum concentration of the drug (Cmax), or area under the plasma concentration versus time curve (AUC) and coagulation times or complement levels. Dose escalation was discontinued because of the attainment of peak plasma concentrations, which approached that associated with complement activation in primates. Two patients with non-Hodgkin's lymphoma who completed 17 and nine cycles of therapy achieved complete responses. The pharmacokinetic profile of ISIS 3521 revealed a short elimination half-life (18 to 92 minutes), as well as a dose-dependent decrease in clearance and dose-dependent increases in Cmax, AUC, and elimination half-life. CONCLUSION: No dose-limiting toxicity of ISIS 3521 was identified, and clinical activity was observed. A short elimination half-life was identified, which suggests that alternate schedules with prolonged administration may be necessary for further clinical development.
Assessing the Reliability of Patient, Nurse, and Family Caregiver Symptom Ratings in Hospitalized Advanced Cancer Patients
Authors: Nekolaichuk Cheryl L. , Maguire Thomas O. , Suarez-Almazor Maria , Rogers W. Todd , Bruera Eduardo 
Published: February 2017

PURPOSE: The purpose of this study was to examine the reliability of symptom assessments in advanced cancer patients under various conditions, including multiple raters (patients, nurses, and family caregivers), occasions, and symptoms. PATIENTS AND METHODS: The study sample consisted of 32 advanced cancer patients admitted to a tertiary palliative care unit. Symptom assessments were completed for each patient on two separate occasions, approximately 24 hours apart. On each occasion, the patient, the primary care nurse, and a primary family caregiver independently completed an assessment using the Edmonton Symptom Assessment System (ESAS). The ESAS is a nine-item visual analogue scale for assessing symptoms in palliative patients. The reliability of the assessments (r) was examined using generalizability theory. RESULTS: Three important findings emerged from this analysis. First, the analysis of individual symptom ratings provided a more meaningful representation of the symptom experience than total symptom distress ratings. Secondly, patients, nurses, and caregivers varied in their ratings across different patients, as well as in their ratings of shortness of breath, which may have been a result of individual rater variability. Finally, reliability estimates (r), based on a single rater and one occasion, were less than .70 for all symptoms, except appetite. These estimates improved substantially (r ≥ .70) for all symptoms except anxiety and shortness of breath, using three raters on a single occasion or two raters across two occasions. CONCLUSION: The findings from this study reinforce the need for the development of an integrated symptom assessment approach that combines patient and proxy assessments. Further research is needed to explore individual differences among raters.
Improved Survival of Children With Isolated CNS Relapse of Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study
Authors: Ritchey A. Kim , Pollock Brad H. , Lauer Stephen J. , Andejeski Yvonne , Buchanan George R. 
Published: February 2017

PURPOSE: Isolated meningeal relapse in children with acute lymphoblastic leukemia (ALL) usually has been followed by bone marrow relapse and limited survival. The purpose of this study was to prevent marrow relapse by administering intensive therapy before delayed craniospinal radiation. PATIENTS AND METHODS: Eighty-three patients with ALL in first bone marrow remission with an isolated CNS relapse were treated with systemic chemotherapy known to enter into the CSF and intrathecal chemotherapy for 6 months. Craniospinal irradiation (24 Gy cranial/15 Gy spinal) was then administered, followed by 1.5 years of maintenance chemotherapy. RESULTS: All 83 patients achieved a second remission. The 4-year event-free survival (EFS) rate was 71.1% ± 5.3%. There was a fourfold increased risk of relapse for children whose initial remission was less than 18 months. The 4-year EFS rate for patients with a first complete remission ≥ 18 months was 83.3% ± 5.3%, and for those with a first complete remission less than 18 months, it was 46.2% ± 10.2% (P = .0002.) There was a low incidence of neurologic toxicity and an unexpectedly high rate of allergic reactions to l-asparaginase. Five patients developed secondary malignancies: two with acute nonlymphoblastic leukemia during therapy, one with myelodysplasia after therapy, and two with brain tumors 1.5 to 2 years after cessation of therapy. CONCLUSION: For children with ALL and an isolated CNS relapse, treatment that delays definitive craniospinal irradiation by 6 months to allow for more intensive systemic and intrathecal chemotherapy results in better EFS than has been previously reported. Using this approach, the long-term prognosis for children with first complete remission ≥ 18 months is comparable to that at the time of original diagnosis of ALL.
Ifosfamide, Carboplatin, and Etoposide: A Highly Effective Cytoreduction and Peripheral-Blood Progenitor-Cell Mobilization Regimen for Transplant-Eligible Patients With Non-Hodgkin's Lymphoma
Authors: Moskowitz Craig H. , Bertino Joseph R. , Glassman Jill R. , Hedrick Eric E. , Hunte Sonia , Coady-Lyons Nancy , Agus David B. , Goy Andre , Jurcic Joseph , Noy Ariela , O'Brien James , Portlock Carol S. , Straus David S. , Childs Barrett , Frank Richard , Yahalom Joachim , Filippa Daniel , Louie Diane , Nimer Stephen D. , Zelenetz Andrew D. 
Published: February 2017

PURPOSE: To evaluate a chemotherapy regimen that consisted of ifosfamide administered as an infusion with bolus carboplatin, and etoposide (ICE) supported by granuloctye colony-stimulating factor (G-CSF) for cytoreduction and stem-cell mobilization in transplant-eligible patients with primary refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred sixty-three transplant-eligible patients with relapsed or primary refractory NHL were treated from October 1993 to December 1997 with ICE chemotherapy at Memorial Sloan-Kettering Cancer Center. Administration of three cycles of ICE chemotherapy was planned at 2-week intervals. Peripheral-blood progenitor cells were collected after cycle 3, and all patients who achieved a partial response (PR) or complete response (CR) to ICE chemotherapy were eligible to proceed to transplantation. Event-free and overall survival, ICE-related toxicity, and the number of CD34+ cells collected after treatment with ICE and G-CSF were evaluated. RESULTS: All 163 patients were assessable for response, and there was no treatment-related mortality. A major response (CR/PR) was evident in 108 patients (66.3%); 89% of the responding patients underwent successful transplantation. Patient who underwent transplantation and achieved a CR to ICE had a superior overall survival to that of patients who achieved a PR (65% v 30%; P = .003). The median number of CD34+ cells/kg collected was 8.4 × 106. The dose-limiting toxicity of ICE was hematologic, with 29.4% of patients developing grade 3/4 thrombocytopenia. There were minimal nonhematologic side effects. CONCLUSION: ICE chemotherapy, with ifosfamide administered as a 24-hour infusion to decrease CNS side effects, and the substitution of carboplatin for cisplatin to minimize nephrotoxicity, is a very effective cytoreduction and mobilization regimen in patients with NHL. Furthermore, the quality of the clinical response to ICE predicts for posttransplant outcome.
Clinical Course of Breast Cancer Patients With Complete Pathologic Primary Tumor and Axillary Lymph Node Response to Doxorubicin-Based Neoadjuvant Chemotherapy
Authors: Kuerer Henry M. , Newman Lisa A. , Smith Terry L. , Ames Fred C. , Hunt Kelly K. , Dhingra Kapil , Theriault Richard L. , Singh Gurpreet , Binkley Susan M. , Sneige Nour , Buchholz Thomas A. , Ross Merrick I. , McNeese Marsha D. , Buzdar Aman U. , Hortobagyi Gabriel N. , Singletary S. Eva 
Published: February 2017

PURPOSE: To assess patient and tumor characteristics associated with a complete pathologic response (pCR) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer (LABC). PATIENTS AND METHODS: Three hundred seventy-two LABC patients received treatment in two prospective neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy. Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy. Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics. Median follow-up was 58 months (range, 8 to 99 months). RESULTS: The initial nodal status, age, and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR (P > .05). Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)–negative (P < .01), and anaplastic (P = .01) but of smaller size (P < .01) than those of patients with less than a pCR. Upon multivariate analysis, the effects of ER status and nuclear grade were independent of initial tumor size. Sixteen percent of the patients in this study (n = 60) had a pathologic complete primary tumor response. Twelve percent of patients (n = 43) had no microscopic evidence of invasive cancer in their breast and axillary specimens. A pathologic complete primary tumor response was predictive of a complete axillary lymph node response (P < .01). The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR (89% and 87%, respectively) than in the group who had less than a pCR (64% and 58%, respectively; P < .01). CONCLUSION: Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery. Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate. However, a pCR does not entirely eliminate recurrence. Further efforts should focus on elucidating the molecular mechanisms associated with this response.
Multicenter Phase II Study of Capecitabine in Paclitaxel-Refractory Metastatic Breast Cancer
Authors: Blum Joanne L. , Jones Stephen E. , Buzdar Aman U. , LoRusso Patricia Mucci , Kuter Irene , Vogel Charles , Osterwalder Bruno , Burger Hans-Ulrich , Brown Cheryl Stoner , Griffin Tom 
Published: February 2017

PURPOSE: Capecitabine is a novel, oral, selectively tumor-activated fluoropyrimidine carbamate. This large multicenter phase II trial tested the efficacy and safety of twice-daily oral capecitabine at 2,510 mg/m2/d given for 2 weeks followed by a 1-week rest period and repeated in 3-week cycles, in patients with paclitaxel-refractory metastatic breast cancer. PATIENTS AND METHODS: Patients were to have received at least two but not more than three prior chemotherapeutic regimens, one of which had to have contained paclitaxel given for metastatic disease. One hundred sixty-three patients were entered onto the study at 25 centers, and 162 patients received capecitabine. One hundred thirty-five patients had bidimensionally measurable disease, and 27 patients had assessable disease. RESULTS: The overall response rate was 20% (95% confidence interval, 14% to 28%). All responding patients were resistant to or had failed paclitaxel, and all had received an anthracycline. Three complete responses were seen, with complete response durations of 106, 109, and 194+ days. Median duration of response was 8.1 months, median survival time was 12.8 months, and the median time to disease progression was 93 days. The most common treatment-related adverse events were hand-foot syndrome, diarrhea, nausea, vomiting, and fatigue. Diarrhea (14%) and hand-foot syndrome (10%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity in more than 10% of patients. CONCLUSION: Capecitabine is an active drug in the treatment of paclitaxel-refractory metastatic breast cancer. It has a favorable toxicity profile with the added advantage of being an oral drug administered at home.
Phase II Trial of Gemcitabine in Refractory Germ Cell Tumors
Authors: Einhorn Lawrence H. , Stender Michael J. , Williams Stephen D. 
Published: February 2017

PURPOSE: This phase II study was designed to determine the toxicity and activity of single-agent gemcitabine in heavily pretreated patients with germ cell tumors. PATIENTS AND METHODS: From March 1996 through November 1997, 21 patients were enrolled onto a phase II study of gemcitabine 1,200 mg/m2, given on days 1, 8, and 15 every 4 weeks. One patient was unassessable because he never received any gemcitabine. Thirteen of 20 patients had received three prior regimens, and 13 patients were platinum refractory (progression during or within 4 weeks of platinum treatment). There were five extragonadal cases and two patients with late relapse (relapse beyond 2 years). RESULTS: Gemcitabine was well tolerated. Only one patient had grade 3 or 4 nonhematologic toxicity (grade 3 nausea). Six of 20 patients had grade 3 leukopenia. There were no episodes of granulocytopenic fever, and no patient required platelet transfusion. Three (15%) of 20 patients achieved an objective response, including one complete remission. Three additional patients had a minor radiographic or serologic response. CONCLUSION: Gemcitabine had definite activity in this heavily pretreated germ cell tumor patient population.
Autotransplants for Hodgkin's Disease in Patients Never Achieving Remission: A Report From the Autologous Blood and Marrow Transplant Registry
Authors: Lazarus By Hillard M. , Rowlings Philip A. , Zhang Mei-Jie , Vose Julie M. , Armitage James O. , Bierman Philip J. , Gajewski James L. , Gale Robert Peter , Keating Arm , Klein John P. , Miller Carole B. , Phillips Gordon L. , Reece Donna E. , Sobocinski Kathleen A. , van Besien Koen , Horowitz Mary M. 
Published: February 2017

PURPOSE: Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (ie, those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed. RESULTS: Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted ofbone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, “B” symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome. CONCLUSION: Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy.
Secondary Leukemia or Myelodysplastic Syndrome After Treatment With Epipodophyllotoxins
Authors: Smith Malcolm A. , Rubinstein Lawrence , Anderson James R. , Arthur Diane , Catalano Paul J. , Freidlin Boris , Heyn Ruth , Khayat Anita , Krailo Mark , Land Vita J. , Miser James , Shuster Jonathan , Vena Don 
Published: February 2017

PURPOSE: The incidence of secondary leukemia after epipodophyllotoxin treatment and the relationship between epipodophyllotoxin cumulative dose and risk are not well characterized. The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of secondary leukemia after epipodophyllotoxin treatment. METHODS: Twelve NCI-supported cooperative group clinical trials were identified that use epipodophyllotoxins at low (< 1.5 g/m2 etoposide), moderate (1.5 to 2.99 g/m2 etoposide), or higher (≥ 3.0 g/m2 etoposide) cumulative doses. Cases of secondary leukemia (including treatment-related myelodysplastic syndrome) occurring on these trials have been reported to CTEP, as has duration of follow-up for all patients, thereby allowing calculation of cumulative 6-year incidence rates of secondary leukemia for each etoposide dose group. RESULTS: The calculated cumulative 6-year risks for development of secondary leukemia for the low, moderate, and higher cumulative dose groups were 3.3%, (95% upper confidence bound of 5.9%), 0.7% (95% upper confidence bound of 1.6%), and 2.2%, (95% upper confidence bound of 4.6%), respectively. CONCLUSION: Within the context of the epipodophyllotoxin cumulative dose range and schedules of administration encompassed by the monitoring plan regimens, and within the context of multiagent chemotherapy regimens that include alkylating agents, doxorubicin, and other agents, factors other than epipodophyllotoxin cumulative dose seem to be of primary importance in determining the risk of secondary leukemia. Data obtained by the CTEP secondary leukemia monitoring plan support the relative safety of using epipodophyllotoxins according to the therapeutic plans outlined in the monitored protocols.
Role of Transforming Growth Factor-β1 in Invasion and Metastasis in Gastric Carcinoma
Authors: Maehara Yoshihiko , Kakeji Yoshihiro , Kabashima Akira , Emi Yasunori , Watanabe Akihiro , Akazawa Kohei , Baba Hideo , Kohnoe Shunji , Sugimachi Keizo 
Published: February 2017

PURPOSE: Transforming growth factor-beta1 (TGF-β1) is a major modulator of cellular proliferation and extracellular matrix formation. We determined the role of TGF-β1 in invasion and metastasis in gastric cancer. MATERIALS AND METHODS: We detected TGF-β1 expression in primary and lymph node metastatic lesions of gastric cancer, using an antibody and in situ hybridization. The plasma TGF-β1 levels in the peripheral vein and in the tumor drainage vein were assayed. RESULTS: In the cytoplasm of cancer cells, TGF-β1 was immunostained in 35.9% (78 of 217) of primary gastric carcinomas, and this expression was confirmed by in situ hybridization. Of 59 gastric carcinomas with a TGF-β1–negative primary tumor, metastatic lymph nodes were positive for TGF-β1 staining in 32 cases (54.2%). Positive staining of TGF-β1 in gastric cancer tissues was closely related to serosal invasion, infiltrative growth, and lymph node metastasis. Multivariate analysis showed that the expression of TGF-β1 was an independent risk factor for serosal invasion and infiltrative growth of the tumor. The plasma level of TGF-β1 did not differ between TGF-β1–negative and –positive groups. There were also no differences in plasma TGF-β1 levels among each tumor stage, between the peripheral and the tumor drainage veins, and between preoperative and postoperative testings. CONCLUSION: Transforming growth factor-β1 is closely related to the invasion and metastasis of gastric cancer, and production of TGF-β1 in the tumor does not contribute to the total amount of TGF-β1 in the blood circulation. We interpret our observations to mean that in a tumor microenvironment, TGF-β1 alters the biologic behavior of the tumor.
Topotecan Versus Cyclophosphamide, Doxorubicin, and Vincristine for the Treatment of Recurrent Small-Cell Lung Cancer
Authors: von Pawel Joachim , Schiller Joan H. , Shepherd Frances A. , Fields Scott Z. , Kleisbauer J.P. , Chrysson Nick G. , Stewart David J. , Clark Peter I. , Palmer Martin C. , Depierre Alain , Carmichael James , Krebs Jacqueline B. , Ross Graham , Lane Stephen R. , Gralla Richard 
Published: February 2017

PURPOSE: Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-cell lung cancer (SCLC) who had relapsed at least 60 days after completion of first-line therapy. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg) infused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic review. RESULTS: Response rate was 26 of 107 patients (24.3%) treated with topotecan and 19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The proportion of patients who experienced symptom improvement was greater in the topotecan group than in the CAV group for four of eight symptoms evaluated, including dyspnea, anorexia, hoarseness, and fatigue, as well as interference with daily activity (P ≤ .043). Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P < .001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P < .001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both regimens. CONCLUSION: Topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC and resulted in improved control of several symptoms.