bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.
Authors: Locatelli F , Niemeyer C , Angelucci E , Bender-Götze C , Burdach S , Ebell W , Friedrich W , Hasle H , Hermann J , Jacobsen N , Klingebiel T , Kremens B , Mann G , Pession A , Peters C , Schmid H J , Stary J , Suttorp M , Uderzo C , van't Veer-Korthof E T , Vossen J , Zecca M , Zimmermann M 
Published: February 2017

PURPOSE To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.
Detection of circulating tumor cells in patients with Ewing's sarcoma and peripheral primitive neuroectodermal tumor.
Authors: West D C , Grier H E , Swallow M M , Demetri G D , Granowetter L , Sklar J 
Published: February 2017

PURPOSE To determine the feasibility of detecting Ewing's sarcoma (ES) or peripheral primitive neuroectodermal tumor (PNET) through a reverse-transcriptase polymerase chain reaction (RT-PCR) of the t(11;22)(q24;q12) fusion transcript in blood and bone marrow samples from patients with these neoplasms. PATIENTS AND METHODS Peripheral-blood (PB) and/or bone marrow aspirate (BM) samples were obtained from 28 patients with ES or PNET at initial presentation or at relapse. Patients were divided into two groups: newly diagnosed patients with nonmetastatic disease and those with metastatic/relapsed disease. RNA was extracted from fractionated BM and PB samples, and RT-PCR was performed for the EWS/HumFLI1 fusion mRNA was transcribed across the t(11;22) breakpoint. RESULTS Among the 16 patients with nonmetastatic disease, three of 16 were RT-PCR positive for EWS/HumFLI1 RNA in BM and three of 10 were positive in PB. The total number of nonmetastatic patients who were positive in either PB or BM was four of 16 (25%). Among patients with metastatic/relapsed disease, two of six were positive in BM and five of 10 were positive in PB. The total fraction of patients with metastatic/relapsed disease that was positive in either BM or PB was six of 12 (50%). CONCLUSION In this study, we show that it is possible to amplify the EWS/HumFLI1 RNA by RT-PCR from the BM and PB of a subset of patients with both nonmetastatic and metastatic ES or PNET, which implies that occult tumor cells are present at these sites. The true biologic and clinical meaning of this information is unknown. However, it does suggest a possible application of RT-PCR for the monitoring of residual disease in patients who are undergoing therapy for ES or PNET. This approach may permit early identification of patients who may benefit from alternative therapy or who may be spared possible overtreatment.
Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma.
Authors: Witte R S , Elson P , Bono B , Knop R , Richardson R R , Dreicer R , Loehrer P J 
Published: February 2017

PURPOSE Alkylating agents have modest activity in advanced urothelial carcinoma. Ifosfamide (IFX) is an agent as yet unstudied in advanced urothelial carcinoma. Despite recent advances in the treatment of this disease, there continues to be a need to identify new active agents and their toxicity spectra. Here we report results from the use of IFX in this population. PATIENTS AND METHODS Ambulatory patients with advanced urothelial carcinoma were treated with IFX 3,750 mg/m2 and mesna 2250 mg/m2 both intravenously (IV) daily for 2 days every 3 weeks. Significant renal and CNS toxicity required a dose change of IFX to 1,500 mg/m2 IV with mesna 750 mg/m2 IV for 5 days every 3 weeks. Doses were modified for hematologic, renal, and CNS toxicity. RESULTS Of 56 eligible patients entered onto the study, 26 received the 2-day schedule and 30 were treated on the 5-day regimen. All patients had progressive disease following prior systemic chemotherapy. There were five complete responses (CRs) and six partial responses (PRs) for an overall response rate of 20% (exact 95% confidence interval [CI], 10% to 32%). Renal and CNS toxicity was severe before the change in schedule, but manageable after the change. Major identified toxicities were gastrointestinal, myelosuppressive, renal, and CNS. There were four early deaths to which treatment probably contributed, but were multifactorial in etiology. CONCLUSION IFX has significant activity, but also major toxicity in a heavily cisplatin-pretreated cohort with advanced urothelial carcinoma. A modification of dose and/or schedule from that described should be considered in future trials. Combination regimens using this agent should be explored.
Analysis of the cost-effectiveness of paclitaxel as alternative combination therapy for advanced ovarian cancer.
Authors: McGuire W , Neugut A I , Arikian S , Doyle J , Dezii C M 
Published: February 2017

PURPOSE A phase III trial by the Gynecologic Oncology Group (GOG) provides strong evidence that a new alternative therapy--paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) in combination with cisplatin (Platinol; Bristol-Myers Squibb Co)--is clinically more effective than the standard therapy using cyclophosphamide (Cytoxan; Bristol-Myers Squibb Co) in combination with cisplatin in the treatment of advanced ovarian cancer. We conducted a pharmacoeconomic analysis to determine whether the alternative paclitaxel-cisplatin (TP) therapy is cost-effective (CE) in comparison to standard cyclophosphamide-cisplatin (CP) therapy. METHODS Using an economic model, we applied cost data figures to resource utilization data derived from the two arms of the GOG trial. We examined paclitaxel benefits in terms of increased mean survival time, as well as median survival time. Estimates of the cumulative proportion surviving in the trial were based on Kaplan-Meier procedures. RESULTS Per year of life gained (YLG), TP therapy costs more ($19,820 more for inpatient treatment; $21,222 outpatient) than CP treatment. CONCLUSION The TP regimen's increased mean survival cost per YLG (inpatient and outpatient settings) adds a substantial benefit at an acceptable cost compared with CP therapy.
Repetitive cycles of cyclophosphamide, thiotepa, and carboplatin intensification with peripheral-blood progenitor cells and filgrastim in advanced breast cancer patients.
Authors: Shapiro C L , Ayash L , Webb I J , Gelman R , Keating J , Williams L , Demetri G , Clark P , Elias A , Duggan D , Hayes D , Hurd D , Henderson I C 
Published: February 2017

PURPOSE As an alternative to single-cycle cyclophosphamide, thiotepa, and carboplatin (CTCb) intensification, we evaluated the feasibility of administering one-quarter dose CTCb for four cycles with peripheral-blood progenitor-cell (PBPC) and filgrastim (granulocyte colony-stimulating factor [G-CSF]) in advanced-stage breast cancer patients. PATIENTS AND METHODS From June 1992 to August 1993, 20 stage IIIB (n = 7) and IV (n = 13) breast cancer patients received 78 cycles of induction with doxorubicin 90 mg/m2 by intravenous (IV) bolus with G-CSF 5 microg/kg/d by subcutaneous injection (SC) repeated every 14 to 21 days for four cycles. PBPC were collected by 2-hour single-blood volume leukapheresis on 2 consecutive days at the time of hematologic recovery from each cycle of doxorubicin. Eighteen patients received 61 cycles of intensification with cyclophosphamide 1,500 mg/m2, thiotepa 125 mg/m2, and carboplatin 200 mg/m2 by IV continuous infusion with G-CSF 10 microg/kg/d SC and PBPC support repeated every 21 to 42 days for four cycles. RESULTS Twelve of 20 patients (60%) completed all four planned cycles of doxorubicin induction followed by four cycles of one-quarter dose CTCb intensification. Statistically significantly decreases in the yield of mononuclear cells (MNC) (median slope per day, -0.032; P = .03), granulocyte-macrophage colony-forming unit (CFU-GM) (median slope per day, -0.57; P = .0008), and burst-forming unit-erythroid (BFU-E) (median slope per day, -1.18; P = .006) were observed over the course of the eight leukaphereses. Of 18 patients who began CTCb, 12 (67%) completed four cycles. Six patients were removed from study during intensification: two for progressive disease (PD), one refused further treatment, and three for dose-limiting hematologic toxicity. A fourth patient fulfilled the criteria for dose-limiting hematologic toxicity after cycle 4. The toxicity of the multiple cycle CTCb intensification regimen consisted of grade IV leukopenia, grade IV thrombocytopenia, and febrile neutropenia in 100%, 100%, and 26% of cycles, respectively. The median duration of each CTCb cycle was 24 days (range, 18 to 63), and the median duration of an absolute neutrophil count (ANC) < or = 500/microL and platelet count < or = 20,000/microL during each cycle was 6 days (range, 2 to 15) and 4 days (range, 0 to 38), respectively. CONCLUSION It is feasible to administer repetitive cycles of one-quarter dose CTCb intensification with PBPC and G-CSF. Additional studies are required to determine whether multiple cycles of CTCb intensification might offer a therapeutic advantage over a single high-dose cycle.
Reappraisal of the role of axillary lymph node dissection in the conservative treatment of breast cancer.
Authors: Haffty B G , Ward B , Pathare P , Salem R , McKhann C , Beinfield M , Fischer D , Reiss M 
Published: February 2017

PURPOSE The purpose of this study was (1) to review systemic therapy practice patterns to assess how information regarding nodal status currently influences systemic therapy decisions, and (2) to review long-term outcome of patients who do not undergo axillary dissection compared with patients who do. METHODS AND MATERIALS For the current practice patterns portion of the study, the records of 292 patients who presented in the past 3 years with invasive breast cancer and underwent conservative surgery were reviewed to determine systemic therapy administered with respect to patient age, primary tumor size, clinical nodal status, and presenting symptoms. For the long-term outcome portion of the study, the records of 955 patients with invasive breast cancer who underwent conservative surgery and radiation therapy before December 1989 were reviewed. Patient characteristics and outcome of those patients who underwent axillary dissection (n = 565, 59%) were compared with a cohort of patients treated during the same era who did not undergo axillary dissection (n = 390, 41%). RESULTS For the current practice-patterns cohort, information regarding nodal status appeared to influence adjuvant systemic therapy for those patients less than 50 years of age and for those patients with palpable masses who were older than 50. Patients older than 50 with nonpalpable mammographically detected tumors have a low probability of nodal involvement and information regarding nodal status rarely changed therapy in this group of patients. In the long-term outcome study, there were no significant differences in the rates of distant metastasis, disease-free survival, or overall survival between those patients who underwent lymph node dissection and those who did not. CONCLUSION For selected patients, axillary lymph node dissection appears to have little influence on subsequent management and long-term outcome. These data suggest that it is time to reassess the role of axillary lymph node dissection in patients who undergo conservative surgery and radiation therapy.
Phase I trial of tirapazamine in combination with cisplatin in a single dose every 3 weeks in patients with solid tumors.
Authors: Johnson C A , Kilpatrick D , von Roemeling R , Langer C , Graham M A , Greenslade D , Kennedy G , Keenan E , O'Dwyer P J 
Published: February 2017

PURPOSE AND METHODS Tirapazamine (SR4233, WIN 59075) is a benzotriazine-di-N-oxide bioreductive agent that is selectively activated to a reactive DNA-damaging species in hypoxic tumors. Preclinical studies show that synergistic antitumor activity results from a schedule-dependent interaction between tirapazamine and several cytotoxic drug classes, including cisplatin. In a phase I combination study, tirapazamine (130 to 260 mg/m2) was administered as a 1-hour intravenous (IV) infusion beginning 3 hours before cisplatin (75 to 100 mg/m2). Thirteen patients received 41 courses of therapy. These patients had an excellent performance status and were not heavily pretreated. The predominant diagnosis was lung cancer. RESULTS The major acute side effects were nausea and vomiting, which were controlled with an intensive antiemetic regimen. Other acute effects included diarrhea and muscle cramping, while with repeated dosing, anorexia and fatigue predominated. Full doses of each agent were well tolerated in combination, although in this previously treated population, fatigue increased markedly after three cycles of therapy. Partial responses were observed in two patients (one with non-small-cell lung cancer and one with breast cancer), and a minor response occurred in a patient with mesothelioma. Tirapazamine pharmacokinetics were linear with respect to increasing dose with a mean maximum plasma concentration (Cmax) of 5.97 +/- 2.25 microg/mL and an area under the concentration-time curve (AUC) of 811.4 +/- 311.9 microg/mL.min at 260 mg/m2. These results are consistent with other ongoing single-agent and combination studies and indicate that therapeutically relevant levels of tirapazamine are achievable in patients based on animal models. The mean cisplatin AUC was 285.6 +/- 46.4 microg/mL.min with mean Cmax values of 3.38 +/- 0.43 microg/mL at 75 mg/m2. The clearance of cisplatin was unaffected by coadministration with tirapazamine. CONCLUSION This trial shows that in previously treated patients, full doses of cisplatin are well tolerated with increasing doses of tirapazamine up to 260 mg/m2. The observation of clinical responses in this trial supports the phase II investigation of this regimen.
Initial clinical trial of a selective retinoid X receptor ligand, LGD1069.
Authors: Miller V A , Benedetti F M , Rigas J R , Verret A L , Pfister D G , Straus D , Kris M G , Crisp M , Heyman R , Loewen G R , Truglia J A , Warrell R P 
Published: February 2017

PURPOSE The retinoid response is mediated by nuclear receptors, including retinoic acid receptors (RARs) and retinoid "X" receptors (RXRs). All-trans retinoic acid (RA) binds only RARs, while 9-cis RA is an agonist for both RARs and RXRs. Recently, LGD1069 was identified as a highly selective RXR agonist with low affinity for RARs. We undertook a dose-ranging study to examine the safety, clinical tolerance, and pharmacokinetics of LGD1069 in patients with advanced cancer. PATIENTS AND METHODS Fifty-two patients received. LGD1069 administered orally once daily at doses that ranged from 5 to 500 mg/m2 for 1 to 41 weeks. Treatment proceeded from a starting dose of 5 mg/m2. Pharmacokinetic sampling was performed on selected patients on days 1, 15, and 29. RESULTS Reversible, asymptomatic increases in liver biochemical tests were the most common dose-limiting adverse effect. Less prominent reactions included leukopenia, hypertriglyceridemia, and hypercalcemia. Characteristic retinoid toxicities, such as cheilitis, headache, and myalgias/arthralgias, were mild or absent. Two patients with cutaneous T-cell lymphoma experienced major antitumor responses. Pharmacokinetic studies obtained in 27 patients at eight dose levels showed that the day 1 area under the plasma concentration-times-time curves (AUCs) were proportional to dose. At all doses studied, the day 1 AUCs were similar to those on days 15 and 29, indicating a lack of induced metabolism. CONCLUSION LGD1069 is a unique compound that exploits a newly identified pathway of retinoid receptor biology that may be relevant to tumor-cell proliferation and apoptosis. Further investigation of this drug is warranted. Based on the results of this study, a dose of 300 mg/m2 is recommended for single-agent trials.
Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study.
Authors: de Gramont A , Bosset J F , Milan C , Rougier P , Bouché O , Etienne P L , Morvan F , Louvet C , Guillot T , François E , Bedenne L 
Published: February 2017

PURPOSE This multicenter study compared the therapeutic ratio of a monthly schedule of low-dose leucovorin (LV) and fluorouracil (5-FU) bolus with a bimonthly schedule of high-dose LV and 5-FU bolus plus continuous infusion in patients with advanced colorectal cancer. PATIENTS AND METHODS Of the 448 patients randomly assigned to treatment, 433 were assessable. Treatment A was a monthly regimen of intravenous (IV) LV 20 mg/m2 plus bolus 5-FU 425 mg/m2 for 5 days every 4 weeks. Treatment B was a bimonthly regimen of IV LV 200 mg/m2 as a 2-hour infusion followed by bolus 5-FU 400 mg/m2 and 22-hour infusion 5-FU 600 mg/m2 for 2 consecutive days every 2 weeks. Therapy was continued until disease progression. Second-line chemotherapy, which included 5-FU continuous infusion, was allowed in both arms. RESULTS The response rates in 348 patients with measurable lesions were 14.4% (monthly regimen) and 32.6% (bimonthly regimen) (P = .0004). The median progression-free survival times were 22 weeks (monthly regimen) and 27.6 weeks (bimonthly regimen) (P = .0012). The median survival times were 56.8 weeks (monthly regimen) and 62 weeks (bimonthly regimen) (P = .067). Grade 3-4 toxicities occurred in 23.9% of patients in the monthly arm compared with 11.1% of those in the bimonthly arm (P = .0004). Patients in arm A more frequently experienced severe granulocytopenia (7.3% v 1.9%), diarrhea (7.3% v 2.9%), and mucositis (7.3% v 1.9%) than patients in arm B. CONCLUSION The bimonthly regimen was more effective and less toxic than the monthly regimen and definitely increased the therapeutic ratio. However, there was no evidence of increased survival.
Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma.
Authors: Tanigawa N , Amaya H , Matsumura M , Shimomatsuya T 
Published: February 2017

PURPOSE The relationship between the expression of vascular endothelial growth factor (VEGF) and its receptor, KDR, in human gastric carcinoma tissues and tumor angiogenesis, as well as patient outcome, were investigated. MATERIALS AND METHODS One hundred sixty-three primary tumor specimens were investigated by immunohistochemical studies with anti-VEGF, anti-KDR, and anti-CD34 antibodies and by monitoring patients for at least 2 years after surgery. RESULTS For intensity of VEGF staining, 48 tumors were graded as 0, 36 as 1+, 63 as 2+, and 16 as 3+. Tumors with strong VEGF staining, assessed as 2+ and 3+, had significantly higher vascularity than those with weak VEGF. Eighty-eight tumors (54%) were positive for KDR. There was no association between KDR expression and tumor vascularity. No close correlation was found between VEGF and KDR expressions. The Cox proportional hazards model identified intratumoral vessel count as the most significant and independent prognostic factor among various clinicopathologic factors. In contrast, overall survival rates for 84 patients with weak VEGF staining tumors and 79 with strong VEGF staining tumors were not significantly different. Patients with tumors of either localized Borrmann types or well-differentiated histologies, which are found more frequently in tumors with strong VEGF staining, survived significantly longer than those with tumors of either infiltrative Borrmann types or poorly differentiated histologies. CONCLUSION We suggest that expression of VEGF is more frequently found in tumors with well-differentiated histology and plays a role in the promotion of angiogenesis in human gastric carcinomas.
Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis.
Authors: Pao C C , Hor J J , Yang F P , Lin C Y , Tseng C J 
Published: February 2017

PURPOSE To determine the presence of cervical cancer cells in circulating peripheral blood of stage IVb cervical cancer patients with metastasis to distant organs. PATIENTS AND METHODS Cervical cancer tissue from 15 stage IVb cervical cancer patients with metastasis were analyzed for the presence of human papillomavirus (HPV) type 16 DNA by nested polymerase chain reaction (PCR). The presence of transcriptional products of the HPV type 16 E6-transforming gene in the peripheral blood of the same 15 cancer patients was analyzed by reverse transcription and PCR. Cervical tissues and peripheral-blood specimens from 12 normal healthy individuals served as controls. RESULTS Thirteen of 15 (86.7%) cervical cancer tissues from same number of patients were found to contain HPV type 16 DNA. Peripheral-blood specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were found to contain HPV-specific mRNA detectable by reverse transcription (RT) and PCR. Cervical tissues from all 12 normal controls were HPV-free. None of the peripheral-blood specimens from two cervical HPV-negative cancer patients and 12 normal controls contained detectable amounts of mRNA of HPV type 16 E6-transforming gene. CONCLUSION The most likely source of the HPV-specific mRNA detected in the peripheral blood of cervical cancer patients with metastasis is the cervical cancer cells derived from or shed from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a sensitive indicator of circulating cervical cancer cells. If PCR positivity is proven to be able to predict disease progression reliably, these findings may have clinical applications in the treatment of cervical and many other cancers.