bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I and Pharmacologic Study of Oral (PEG-1000) 9-Aminocamptothecin in Adult Patients With Solid Tumors
Authors: de Jonge Maja J.A. , Punt Cornelis J.A. , Gelderblom A. Hans , Loos Walter J. , van Beurden Vera , Planting André S.Th. , van der Burg Maria E.L. , van Maanen Lydia W.G.M. , Dallaire Brian K. , Verweij Jaap , Wagener D.J. Theo , Sparreboom Alex 
Published: February 2017

PURPOSE: 9-Amino-20(S)-camptothecin (9-AC) is a specific inhibitor of topoisomerase-I. Recently, a bioavailability of approximately 48% for the oral PEG-1000 formulation was reported. We conducted a phase I and pharmacokinetic study of the oral PEG-1000 formulation of 9-AC to define the maximum-tolerated dose, toxicity profiles, pharmacokinetic-dynamic relationships, and preliminary antitumor activity in patients with solid tumors. PATIENTS AND METHODS: Patients were treated with oral (PEG-1000) 9-AC given once a day for 7 or 14 days at doses ranging from 0.25 to 1.1 mg/m2/d; cycles were repeated every 21 days. For pharmacokinetic analysis, plasma sampling was performed on days 1 and 6 or 8 of the first course using a validated high-performance liquid chromatographic assay. RESULTS: Thirty patients were entered onto the study; three patients were not assessable for toxicity and response. Twenty-seven patients received a total of 89 courses. The dose-limiting toxicities (DLTs) were myelosuppression and diarrhea at a dose of 1.1 mg/m2/d for 14 days. Pharmacokinetics showed a substantial interpatient variation of the area under the plasma concentration-time curve (AUC) of 9-AC. The intrapatient variability was extremely small. A significant correlation was observed between the percentage decrease in WBC count and the AUC of 9-AC lactone (r2 = 0.86). One partial response was noted in a patient with metastatic colorectal cancer. CONCLUSION: DLTs in this phase I study of oral 9-AC daily for 14 days every 21 days were myelosuppression and diarrhea. The recommended dose for phase II studies is 0.84 mg/m2/d. In view of the substantial interpatient variability in AUC and the availability of a limited sampling model, a pharmacokinetic guided phase II study should be considered.
Cisplatin, Gemcitabine, and Paclitaxel in Locally Advanced or Metastatic Non–Small-Cell Lung Cancer: A Phase I-II Study
Authors: Frasci Giuseppe , Panza Nicola , Comella Pasquale , Nicolella Gianpaolo P. , Natale Michele , Manzione Luigi , Bilancia Domenico , Cioffi Riccardo , Maiorino Luigi , De Cataldis Giuseppe , Belli Mario , Micillo Enrico , Mascia Vittorio , Massidda Bruno , Lorusso Vito , De Lena Mario , Carpagnano Francesco , Contu Antonio , Pusceddu Guido , Comella Giuseppe 
Published: February 2017

PURPOSE: Because both cisplatin-paclitaxel and cisplatin-gemcitabine combinations are generally considered to be among the most active regimens in non–small-cell lung cancer (NSCLC) patients, this study aimed to determine the maximum-tolerated dose (MTD) of paclitaxel when combined with fixed doses of cisplatin and gemcitabine in advanced NSCLC patients and aimed to define the therapeutic activity of this new regimen. PATIENTS AND METHODS: From October 1996 to September 1998, 75 patients with stage IIIB-IV NSCLC, who were either chemotherapy-naive (65 patients) or who had been pretreated (10 patients), received fixed doses of cisplatin (50 mg/m2) and gemcitabine (1,000 mg/m2) and escalating doses of paclitaxel in a 1-hour infusion, all on days 1 and 8, every 3 weeks. RESULTS: Five different paclitaxel doses were tested, for a total of 275 cycles delivered. The escalation was stopped at the paclitaxel dose of 75 mg/m2 in pretreated patients, whereas it continued to 150 mg/m2 in chemotherapy-naive patients. A total of 65 chemotherapy-naive patients were treated. A paclitaxel dose of 125 mg/m2 was recommended for phase II, and a total of 39 patients were treated at this level, for a total of 158 cycles delivered. No treatment-related deaths occurred. Five patients were hospitalized because of sepsis, and packed RBC transfusion was required in 13 patients. Grade 4 neutropenia and thrombocytopenia occurred in 23 (31%) and eight (11%) patients, respectively. Overall, 74 of the 75 patients were assessable for response. Four complete (CR) and 38 partial (PR) responses were recorded, for an overall response rate (ORR) of 57%. Three of the ten pretreated patients achieved a PR, compared with four CRs and 35 PRs in the 64 chemotherapy-naive patients (ORR, 61%). Thirty-eight of 39 patients included in phase II were assessable for response and quality of life (QOL) (one patient's disease was not measurable). Two CRs and 24 PRs were recorded in this group, for an ORR of 68% (95% confidence interval, 51% to 82%). The QOL score improved in 27 of 38 (71%) patients. The median survival time was 15 months in the 65 chemotherapy-naive patients, but it had not yet been reached in the 39 patients included in phase II, for whom the 1-year projected survival was 70%. CONCLUSION: The cisplatin-gemcitabine-paclitaxel combination is a feasible and well-tolerated approach in advanced NSCLC patients. Both a major response and a QOL improvement can be obtained in a high proportion of patients, with a median survival time exceeding 1 year. A phase III trial comparing this combination with other effective regimens is under way.
Accuracy of Recall in Health-Related Quality-of-Life Assessment Among Men Treated for Prostate Cancer
Authors: Litwin Mark S. , McGuigan Kimberly A. 
Published: February 2017

PURPOSE: To determine the accuracy of patient recall of health-related quality of life (HRQOL) in men who have undergone radical prostatectomy for early-stage prostate cancer. PATIENTS AND METHODS: Patients enrolled onto a longitudinal, observational cohort study of HRQOL after radical prostatectomy for early-stage prostate cancer were asked to assess their baseline HRQOL before surgery. They were later asked to recall their baseline HRQOL at intervals of 7 to 37 months after surgery. The two views of baseline HRQOL (actual and recall) were compared. HRQOL was measured with established instruments (the RAND 12-Item Short-Form Health Survey and a validated short form of the University of California Los Angeles Prostate Cancer Index) that addressed impairment in the physical, mental, urinary, bowel, and sexual domains. RESULTS: Overall, recall was poor. Patients tended to remember their baseline HRQOL as being better than it actually was. This effect was particularly striking for urinary and sexual function. Greater education and younger age diminished this effect in some domains. The effect did not vary with time since surgery. CONCLUSION: Men undergoing radical prostatectomy for early-stage prostate cancer do not accurately recall their pretreatment HRQOL when asked several months or years later. This recall bias is constant throughout a period of 6 months to 3 years after surgery. By collecting data before treatment and observing subjects longitudinally, investigators can ensure that HRQOL changes are analyzed in the context of any impairment that may have been present at baseline. If a longitudinal study is not feasible, then great caution must be used if patients are asked to recall their pretreatment HRQOL.
Differential Expression of Nuclear Retinoid Receptors in Normal and Malignant Prostates
Authors: Lotan Yair , Xu Xiao C. , Shalev Moshe , Lotan Reuben , Williams Russell , Wheeler Thomas M. , Thompson Timothy C. , Kadmon Dov 
Published: February 2017

PURPOSE: To determine (1) whether nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are differentially expressed in normal and in cancerous human prostate tissues and (2) whether oral fenretinide therapy impacts the expression of these receptors in prostate cancer. PATIENTS AND METHODS: In situ hybridization with antisense riboprobes was used to probe for RAR and RXR transcripts in prostate tissues in a two-phased study: (1) expression of retinoid receptors in eight normal prostates was compared with their expression in 10 randomly picked radical prostatectomy specimens (group A); (2) expression of retinoid receptors was determined in 22 radical prostatectomy specimens from participants in a clinical study (group B). Twelve patients received oral fenretinide 200 mg/d, and 10 received placebo pills for 28 days before surgery. RESULTS: RARα, RARγ, RXRα, and RXRγ mRNAs were detected in most normal and cancerous prostates. In group A, RARβ mRNA was expressed in only four of 10 malignant prostates but was present in seven of eight benign prostates (P = .05). RXRβ mRNA was expressed in four of eight benign prostates and in zero of 10 malignant prostates (P = .023). In group B prostates, RARβ and RXRβ mRNAs were markedly reduced in all cancers and in the adjacent, nonmalignant tissue. There were no differences between receptor expression in the fenretinide-treated group and the placebo group. CONCLUSION: RARβ and RXRβ mRNAs are selectively lost in both prostate cancer and adjacent morphologically normal prostatic tissue, supporting the concept of a field of carcinogenesis. One month of oral fenretinide (200 mg/d) did not influence the expression of retinoid receptors in prostate cancer.
Rifampin Does Not Improve the Efficacy of Quinolone Antibacterial Prophylaxis in Neutropenic Cancer Patients: Results of a Randomized Clinical Trial
Authors: Gomez-Martin Carlos , Solá Claudio , Hornedo Javier , Perea Sofia , Lumbreras Carlos , Valentí Vicente , Arcediano Alberto , Rodriguez Milva , Salazar Ramon , Cortés-Funes Hernán , Hidalgo Manuel 
Published: February 2017

PURPOSE: To determine whether the addition of rifampin to a quinolone-based antibacterial prophylactic regimen in patients undergoing high-dose chemotherapy (HDC) with peripheral-blood stem-cell transplantation (PBSCT) decreases the incidence of neutropenia and fever, Gram-positive bacteremia, and infection-related morbidity. PATIENTS AND METHODS: Patients with solid tumors undergoing HDC with PBSCT were randomized to receive prophylactic antibiotics with either ciprofloxacin 500 mg orally every 8 hours or the same ciprofloxacin regimen with rifampin 300 mg orally every 12 hours. Prophylaxis was started 48 hours before stem-cell reinfusion. Patients were monitored to document the occurrence of neutropenia and fever, incidence and cause of bacterial infection, time to onset and duration of fever, requirement for intravenous antimicrobials, and length of hospital admission. RESULTS: Sixty-five patients were randomized to receive ciprofloxacin and 65 to receive ciprofloxacin plus rifampin, and from these groups, 62 and 61 were assessable, respectively. The proportion of patients who developed neutropenia and fever was 87% in the group treated with ciprofloxacin and 78% in the group treated with ciprofloxacin and rifampin (P = .25). Although there was a trend toward a reduction in the overall incidence of bacteremia (12 v 4 patients), and Gram-positive bacteremia (8 v 2 patients) with the addition of rifampin, none of these comparisons was statistically significant (P = .05 and P = .09, respectively). CONCLUSION: The results of this study, which demonstrate that rifampin does not improve ciprofloxacin antibacterial prophylaxis in cancer patients undergoing HDC with PBSCT support but that it does increase the occurrence of undesirable side effects, do not support the routine use of rifampin in this setting.
Phase I/II Trial of Cyclophosphamide, Mitoxantrone, and Escalated Doses of Carboplatin Supported by Peripheral-Blood Stem Cells in Women With Metastatic Breast Cancer
Authors: Patnaik Amita , MacKinnon Janet , Goss Paul , Nagy Tracy , Stewart Keith , Keating Armand , Crump Michael 
Published: February 2017

PURPOSE: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high complete and overall response rates in metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline-based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m2/d and mitoxantrone 16 mg/m2/d combined with escalating doses of carboplatin 200 to 500 mg/m2/d, each given daily from days −6 to −3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 μg/d subcutaneously starting on day 1. RESULTS: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with ≤ 400 mg/m2 of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 × 109/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 × 109/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). CONCLUSION: The maximum-tolerated dose of carboplatin was 400 mg/m2/d in combination with mitoxantrone 16 mg/m2/d and cyclophosphamide 1,500 mg/m2, all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment.
Mobilization of Peripheral-Blood Stem Cells by Concurrent Administration of Daniplestim and Granulocyte Colony-Stimulating Factor in Patients With Breast Cancer or Lymphoma
Authors: DiPersio John F. , Schuster Michael W. , Abboud Camille N. , Winter Jane N. , Santos Vicki R. , Collins Denise M. , Sherman Jeffrey W. , Baum Charles M. 
Published: February 2017

PURPOSE: To evaluate the safety and hematopoietic activity of daniplestim administered concurrently with granulocyte colony-stimulating factor (G-CSF) for peripheral-blood stem-cell (PBSC) mobilization. PATIENTS AND METHODS: In the initial dose-escalation phase, 25 patients with adenocarcinoma of the breast (AB; 13 patients) or lymphoma (12 patients) were given daniplestim at doses ranging from 0.1 to 3.75 μg/kg/d plus G-CSF 10 μg/kg/d. In the randomized phase, 52 patients with AB (27 patients) or lymphoma (25 patients) were randomized within disease categories to the daniplestim dose chosen in the dose-escalation phase plus G-CSF 10 μg/kg/d (D+G) or placebo plus G-CSF 10 μg/kg/d (P+G) for up to 7 days. RESULTS: A daniplestim dose of 2.5 μg/kg/d was chosen for further study because it was hematopoietically active and had an acceptable side-effect profile. In the randomized phase, in patients with AB, D+G was associated with a higher probability (P = .0696) of collecting ≥ 2.5 × 106 CD34+ cells/kg and significantly higher circulating CD34+ cell counts (P = .0498) on days 6 through 9 after the initiation of dosing. The target level was more likely to be reached with additional leukaphereses in the patients given D+G. Patients given P+G did not benefit from additional leukaphereses beyond the first procedure. The type of mobilization did show a trend toward a shorter duration of neutropenia in the D+G group. The adverse events with D+G consisted largely of mild to moderate flu-like symptoms, including headache and fever, and occurred more frequently than with P+G. CONCLUSION: Daniplestim administered at 2.5 μg/kg/d is tolerable and active when combined with G-CSF, and the combination may prove more effective than G-CSF alone in promoting the collection of adequate numbers of CD34+ cells for PBSC infusion in patients with AB.
Phase I and Pharmacologic Study of Docetaxel and Irinotecan in Advanced Non–Small-Cell Lung Cancer
Authors: Masuda Noriyuki , Negoro Shunichi , Kudoh Shinzoh , Sugiura Takahiko , Nakagawa Kazuhiko , Saka Hideo , Takada Minoru , Niitani Hisanobu , Fukuoka Masahiro 
Published: February 2017

PURPOSE: We conducted a phase I trial of docetaxel, a new antimicrotubule agent, combined with irinotecan (CPT-11), a topoisomerase I inhibitor. The aim was to determine the maximum-tolerated dose (MTD) of docetaxel combined with CPT-11, as well as the dose-limiting toxicities (DLTs) of this combination in advanced non–small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Thirty-two patients with stage IIIB or IV NSCLC were treated at 4-week intervals with docetaxel (60 minutes, day 2) plus CPT-11 (90 minutes, days 1, 8, and 15). The starting doses of docetaxel/CPT-11 were 30/40 mg/m2, and doses were escalated in 10-mg/m2 increments until the MTD was reached. RESULTS: The MTD of docetaxel/CPT-11 was 50/60 mg/m2 (level 5A), or 60/50 mg/m2 (level 5B). Neutropenia and diarrhea were the DLTs. CPT-11 did not affect the pharmacokinetics of docetaxel. There were 11 (37%) partial responses among 30 patients. The median survival time was 48 weeks, and the 1-year survival rate was 44.9%. CONCLUSION: The combination of docetaxel and CPT-11 seems to be active against NSCLC, with acceptable toxicity. The recommended dose for phase II studies is 50 mg/m2 of CPT-11 (days 1, 8, and 15) and 50 mg/m2 of docetaxel (day 2) administered every 28 days.
Differential Frequencies of p16INK4a Promoter Hypermethylation, p53 Mutation, and K-ras Mutation in Exfoliative Material Mark the Development of Lung Cancer in Symptomatic Chronic Smokers
Authors: Kersting M. , Friedl C. , Kraus A. , Behn M. , Pankow W. , Schuermann M. 
Published: February 2017

PURPOSE: The aim of this study was to investigate the frequency of three (epi)genetic alterations (p53 and K-ras mutations and p16INK4a promoter hypermethylation) in symptomatic chronic smokers compared with patients with lung cancer and to evaluate the use of exfoliative material for such analyses. PATIENTS AND METHODS: Fifty-one patients with histologically confirmed lung cancer and 25 chronic smokers (> 20 pack-years) were investigated for mutations in the K-ras (codon 12) and p53 (codons 248, 249, and 273) genes and for allelic hypermethylation of the p16INK4a gene. DNA was isolated from sputum and bilateral bronchial lavage, and brushings were taken at bronchoscopy. RESULTS: Forty-one genetic lesions were detected within exfoliative material from the group of 51 patients with lung cancer and 10 lesions in the chronic smoker group. K-ras mutations occurred exclusively in the lung cancer group, whereas p53 mutations and p16INK4a promoter hypermethylation were also found in chronic smokers. Three of eight chronic smokers who harbored an (epi)genetic alteration were subsequently diagnosed with lung cancer. Analysis of sputum yielded information equivalent to that of samples obtained during bronchoscopy. CONCLUSION: p16INK4a promoter hypermethylation and p53 mutations can occur in chronic smokers before any clinical evidence of neoplasia and may be indicative of an increased risk of developing lung cancer or of early disease. K-ras mutations occur exclusively in the presence of clinically detectable neoplastic transformation. Molecular analysis of sputum for such markers may provide an effective means of screening chronic smokers to enable earlier detection and therapeutic intervention of lung cancer.
Late Effects of Treatment in Survivors of Childhood Acute Myeloid Leukemia
Authors: Leung Wing , Hudson Melissa M. , Strickland Donald K. , Phipps Sean , Srivastava Deo K. , Ribeiro Raul C. , Rubnitz Jeffrey E. , Sandlund John T. , Kun Larry E. , Bowman Laura C. , Razzouk Bassem I. , Mathew Prasad , Shearer Patricia , Evans William E. , Pui Ching-Hon 
Published: February 2017

PURPOSE: To investigate the incidence of and risk factors for late sequelae of treatment in patients who survived for more than 10 years after the diagnosis of childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: Of 77 survivors (median follow-up duration, 16.7 years), 44 (group A) had received chemotherapy, 18 (group B) had received chemotherapy and cranial irradiation, and 15 (group C) had received chemotherapy, total-body irradiation, and allogeneic bone marrow transplantation. Late complications, tobacco use, and health insurance status were assessed. RESULTS: Growth abnormalities were found in 51% of survivors, neurocognitive abnormalities in 30%, transfusion-acquired hepatitis in 28%, endocrine abnormalities in 16%, cataracts in 12%, and cardiac abnormalities in 8%. Younger age at the time of diagnosis or initiation of radiation therapy, higher dose of radiation, and treatment in groups B and C were risk factors for the development of academic difficulties and greater decrease in height Z score. In addition, treatment in group C was a risk factor for a greater decrease in weight Z score and the development of growth-hormone deficiency, hypothyroidism, hypogonadism, infertility, and cataracts. The estimated cumulative risk of a second malignancy at 20 years after diagnosis was 1.8% (95% confidence interval, 0.3% to 11.8%). Twenty-two patients (29%) were smokers, and 11 (14%) had no medical insurance at the time of last follow-up. CONCLUSION: Late sequelae are common in long-term survivors of childhood AML. Our findings should be useful in defining areas for surveillance of and intervention for late sequelae and in assessing the risk of individual late effects on the basis of age and history of treatment.
High-Dose Chemotherapy as Initial Salvage Chemotherapy in Patients With Relapsed Testicular Cancer
Authors: Bhatia S. , Abonour R. , Porcu P. , Seshadri R. , Nichols C.R. , Cornetta K. , Einhorn L.H. 
Published: February 2017

PURPOSE: To assess the role of high-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer. PATIENTS AND METHODS: From August 1992 to April 1998, 65 patients with testicular cancer were treated with high-dose carboplatin and etoposide followed by peripheral-blood stem-cell transplantation or autologous bone marrow transplantation rescue as initial salvage chemotherapy at Indiana University. An identical course was given after hematopoietic reconstitution. Postchemotherapy resection of residual disease was performed in selected patients with incomplete radiographic response associated with normalization of markers. The median follow-up was 39 months (range, 16 to 91 months). RESULTS: Thirty-seven (57%) of the 65 patients are continuously disease-free. Three additional patients are disease-free with subsequent surgery. High-dose chemotherapy was associated with significant morbidity but no treatment-related mortality. CONCLUSION: High-dose chemotherapy as initial salvage chemotherapy achieved impressive long-term survival with acceptable toxicity in patients with relapsed testicular cancer.