bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I and Pharmacokinetic Study of Irinotecan and Docetaxel in Patients With Advanced Solid Tumors: Preliminary Evidence of Clinical Activity
Authors: Adjei Alex A. , Klein Cheri E. , Kastrissios Helen , Goldberg Richard M. , Alberts Steven R. , Pitot Henry C. , Sloan Jeff A. , Reid Joel M. , Hanson Lorelei J. , Atherton Pamela , Rubin Joseph , Erlichman Charles 
Published: February 2017

PURPOSE: The goals of this study were to determine the maximum-tolerated dose and describe the toxicities of the combination of irinotecan and docetaxel administered every 3 weeks to patients with advanced malignancies and, also, to evaluate the effect of irinotecan on the disposition of docetaxel and describe preliminary evidence of antitumor activity. PATIENTS AND METHODS: Eighteen patients received 85 courses (median, two courses; range, one to 15 courses) of treatment with irinotecan, administered over 90 minutes by intravenous infusion, followed by docetaxel, administered over 60 minutes by intravenous infusion. Four escalating dose levels of irinotecan/docetaxel (160/50 mg/m2, 160/65 mg/m2, 200/65 mg/m2, and 200/75 mg/m2) were studied. Pharmacokinetic analyses were performed to evaluate the effect of irinotecan on the disposition of docetaxel. RESULTS: The most common and dose-limiting toxicity was myelosuppression, which consisted of neutropenia that was severe (National Cancer Institute common toxicity criteria [NCI CTC] grade 4) but brief (< 5 days) in 11 patients, with three episodes of febrile neutropenia. Nonhematologic toxicities of anorexia, nausea, and stomatitis were mild to moderate (NCI CTC grades 1 and 2), but there was one incidence each of both CTC grade 3 anorexia and nausea. All patients had total alopecia. Diarrhea was dose-dependent and severe in four patients who failed to take adequate antidiarrhea therapy. Five out of 16 assessable patients, one with cholangiocarcinoma, one with leiomyosarcoma, and three with non–small-cell lung cancer, achieved partial remissions. CONCLUSION: The combination of irinotecan and docetaxel causes significant reversible myelosuppression, which was dose limiting but led to no serious sequelae. There was no evidence of a clinically significant interaction using these two agents in this sequence. The combination showed antitumor activity at all the dose levels tested and should be further studied in a number of tumor types. The recommended phase II dose on this schedule is irinotecan 160 mg/m2 and docetaxel 65 mg/m2.
Phase I Study of Paclitaxel in Combination With a Multidrug Resistance Modulator, PSC 833 (Valspodar), in Refractory Malignancies
Authors: Fracasso Paula M. , Westerveldt Peter , Fears Carole A. , Rosen D. Marc , Zuhowski Eleanor G. , Cazenave Lorraine A. , Litchman Manuel , Egorin Merrill J. 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of paclitaxel when given with PSC 833 (valspodar) to patients with refractory solid tumors. PATIENTS AND METHODS: Patients were initially treated with paclitaxel 175 mg/m2 continuous intravenous infusion (CIVI) over 3 hours. Subsequently, 29 hours of treatment with CIVI PSC 833 was started 2 hours before paclitaxel treatment was initiated. In this combination, the starting dose of paclitaxel was 52.5 mg/m2. Paclitaxel doses were escalated by 17.5 mg/m2 increments for four subsequent cohorts. Each cohort consisted of three patients with the exception of the last cohort, which consisted of six patients. Data for the pharmacokinetics of paclitaxel with and without concurrent PSC 833 administration were obtained. RESULTS: All 18 patients completed at least one course of concurrent treatment (median, two courses; range, one to six) and were evaluable for toxicity. The MTD for paclitaxel with PSC 833 was 122.5 mg/m2. Neutropenia was the DLT. All patients had PSC 833 blood concentrations greater than 1,000 ng/mL before, during, and 24 hours after the paclitaxel infusion. PSC 833 produced small increases in the paclitaxel peak plasma concentrations and areas under the concentration-time curve. However, PSC 833 greatly prolonged the terminal phase of paclitaxel, resulting in plasma paclitaxel concentrations of more than 0.05 μmol/L for much longer than expected. As a result, myelosuppression was comparable to that produced by full-dose paclitaxel given without PSC 833. Of the 16 patients who were assessable for response, one patient experienced a partial response and an additional nine patients experienced disease stabilization after paclitaxel treatment alone. CONCLUSION: Treatment with paclitaxel 122.5 mg/m2 as a 3-hour CIVI concurrent with a 29-hour CIVI of PSC 833 results in acceptable toxicity. The addition of PSC 833 alters the pharmacokinetics of paclitaxel, which explains the enhanced neutropenia experienced by patients treated with this drug combination.
Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After High-Dose Therapy With Autologous Hematopoietic Progenitor-Cell Support for Lymphoid Malignancies
Authors: Micallef Ivana N. M. , Lillington Debra M. , Apostolidis John , Amess John A. L. , Neat Michael , Matthews Janet , Clark Taane , Foran James M. , Salam Ashiq , Lister T. Andrew , Rohatiner Ama Z. S. 
Published: February 2017

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q−, 15 had −7/7q−, seven had −18/18q−, seven had −13/13q−, and four had −20/20q−. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P = .009) and older age (P = .02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P = .05 and .07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.
Allogeneic Bone Marrow Transplantation for Therapy-Related Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Long-Term Study of 70 Patients—Report of the French Society of Bone Marrow Transplantation
Authors: Yakoub-Agha I. , de La Salmonière P. , Ribaud P. , Sutton L. , Wattel E. , Kuentz M. , Jouet J.P. , Marit G. , Milpied N. , Deconinck E. , Gratecos N. , Leporrier M. , Chabbert I. , Caillot D. , Damaj G. , Dauriac C. , Dreyfus F. , François S. , Molina L. , Tanguy M.L. , Chevret S. , Gluckman E. 
Published: February 2017

PURPOSE: To identify predictive factors of survival, relapse, and transplantation-related mortality (TRM) among patients with therapy-related myelodysplastic syndrome (t-MDS) or acute leukemia (t-AML) who underwent allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From 1980 to 1998, 70 patients underwent allogeneic BMT for t-MDS (n = 31) or t-AML (n = 39) after prior cytotoxic exposure. Thirty-three patients had received induction-type chemotherapy before BMT. At the time of transplantation, there were 24 patients in complete remission (CR) and 46 with active disease. RESULTS: With a median follow-up of 7.9 years (range, 1.1 to 18.8 years) after BMT, 16 patients are alive, whereas 19 died of relapse, 34 of TRM, and one of relapse of the primary disease. The estimated 2-year overall survival, event-free survival, relapse, and TRM rates were 30% (95% confidence interval [CI], 19% to 40%), 28% (95% CI, 18% to 39%), 42% (95% CI, 26% to 57%), and 49% (95% CI, 36% to 62%), respectively. In multivariable analysis, age greater than 37 years, male sex, positive recipient cytomegalovirus (CMV) serology, absence of CR at BMT, and intensive schedules used for conditioning were associated with poor outcome. CONCLUSION: BMT is an effective treatment for patients with t-MDS or t-AML who have responsive disease and, in particular, who have no poor-risk cytogenetic features. The poor results of the other patients, especially those with active disease at BMT, emphasize the need to delineate indications and perform prospective protocols.
Clinical Utility of the Percentage of Positive Prostate Biopsies in Defining Biochemical Outcome After Radical Prostatectomy for Patients With Clinically Localized Prostate Cancer
Authors: D’Amico Anthony V. , Whittington Richard , Malkowicz S. Bruce , Schultz Delray , Fondurulia Julia , Chen Ming-Hui , Tomaszewski John E. , Renshaw Andrew A. , Wein Alan , Richie Jerome P. 
Published: February 2017

PURPOSE: To determine the clinical utility of the percentage of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for men with PSA-detected or clinically palpable prostate cancer. METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men while accounting for the previously established risk groups that are defined according to pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Committee on Cancer (AJCC) clinical T stage. The findings were then tested using an independent surgical database that included data for 823 men. RESULTS: Controlling for the known prognostic factors, the percentage of positive prostate biopsies added clinically significant information (P < .0001) regarding time to PSA failure after RP. Specifically, 80% of the patients in the intermediate-risk group (1992 AJCC T2b, or biopsy Gleason 7 or PSA > 10 ng/mL and ≤ 20 ng/mL) could be classified into either an 11% or 86% 4-year PSA control cohort using the preoperative prostate biopsy data. These findings were validated in the intermediate-risk patients using an independent surgical data set. CONCLUSION: The validated stratification of PSA outcome after RP using the percentage of positive prostate biopsies in intermediate-risk patients is clinically significant. This information can be used to identify men with newly diagnosed and clinically localized prostate cancer who are at high risk for early (≤ 2 years) PSA failure and, therefore, may benefit from the use of adjuvant therapy.
Examining the Role of Neoadjuvant Androgen Deprivation in Patients Undergoing Prostate Brachytherapy
Authors: Potters Louis , Torre Taryn , Ashley Richard , Leibel Steven 
Published: February 2017

PURPOSE: To assess the role of neoadjuvant androgen deprivation (NAAD) and transperineal interstitial permanent prostate brachytherapy (TIPPB) using a matched-pair analysis selected from a large cohort of patients undergoing TIPPB. PATIENTS AND METHODS: Six hundred twelve consecutive patients with clinically confined prostate cancer were treated between June 1992, and January 1997, with permanent ultrasound-guided TIPPB with either palladium-103 or iodine-125 as monotherapy or combined with external radiation. Patients with prostate glands ≥ 60 g underwent treatment with NAAD before TIPPB to reduce the prostate volume (n = 163). The median duration of NAAD was 3.4 months before TIPPB (range, 1 to 8 months). To assess the benefit of NAAD, a matched-pair analysis was performed. The American Society of Therapeutic Radiology and Oncology Consensus Group definition of prostate-specific antigen (PSA) relapse-free survival (RFS) was used with the added caveat of an absolute increase of ≥ 1.0 ng/mL. Differences in pretreatment PSA, Gleason scores, and stage were analyzed by Kaplan-Meier curves and the log-rank test. RESULTS: Two hundred sixty-three patients were matched, with a median follow-up duration of 46 months (range, 24 to 76 months). The actuarial 5-year PSA-RFS rate for all 263 patients is 86.5%. The 5-year PSA-RFS rate for patients treated with NAAD and TIPPB was 87.1% compared with 86.9% for those treated with TIPPB only (P = .935). Subgroup analysis by Gleason score groupings, pretreatment PSA, or stage of disease failed to identify any factors for which androgen ablation was beneficial. CONCLUSION: We were unable to identify any improvement with the addition of NAAD to TIPPB in patients with localized prostate cancer in this retrospective matched-pair analysis. Furthermore, there was no subset for which the addition of NAAD was found to be beneficial. Clarification of the role and duration of NAAD in patients with early-stage prostate cancer will require prospective data.
Sucralfate in the Prevention of Treatment-Induced Diarrhea in Patients Receiving Pelvic Radiation Therapy: A North Central Cancer Treatment Group Phase III Double-Blind Placebo-Controlled Trial
Authors: Martenson James A. , Bollinger John W. , Sloan Jeff A. , Novotny Paul J. , Urias Rodolfo E. , Michalak John C. , Shanahan Thomas G. , Mailliard James A. , Levitt Ralph 
Published: February 2017

PURPOSE: Randomized studies have suggested that sucralfate is effective in mitigating diarrhea during pelvic radiation therapy (RT). This North Central Cancer Treatment Group study was undertaken to confirm the antidiarrheal effect of sucralfate. Several other measures of bowel function were also assessed. PATIENTS AND METHODS: Patients receiving pelvic RT to a minimum of 45 Gy at 1.7 to 2.1 Gy/d were eligible for the study. Patients were assigned randomly, in double-blind fashion, to receive sucralfate (1.5 g orally every 6 hours) or an identical looking placebo during pelvic RT. RESULTS: One hundred twenty-three patients were randomly assigned and found assessable. Overall, there was no significant difference in patient characteristics between those receiving sucralfate and those receiving placebo. Moderate or worse diarrhea was observed in 53% of patients receiving sucralfate versus 41% of those receiving placebo. Compared with patients receiving placebo, more sucralfate-treated patients reported fecal incontinence (16% v 34%, respectively; P = .04) and need for protective clothing (8% v 23%, respectively; P = .04). The incidence and severity of nausea were worse among those taking sucralfate (P = .03). Analysis of patient-reported symptoms 10 to 12 months after RT showed a nonsignificant trend toward more problems in patients taking sucralfate than in those taking placebo (average, 2.3 v 1.9 problems, respectively; P = .34). CONCLUSION: Sucralfate did not decrease pelvic RT-related bowel toxicity by any of the end points measured and seems to have aggravated some gastrointestinal symptoms.
Single-Arm, Open-Label Phase II Study of Intravenously Administered Tirapazamine and Radiation Therapy for Glioblastoma Multiforme
Authors: Del Rowe J. , Scott C. , Werner-Wasik M. , Bahary J.P. , Curran W.J. , Urtasun R.C. , Fisher B. 
Published: February 2017

PURPOSE: This phase II study tested the efficacy and safety of tirapazamine (Sanofi Synthelabo Research, Malvern, PA), a bioreductive agent, in glioblastoma multiforme (GBM) patients. The patients were staged according to a model constructed by a recursive partitioning analysis (RPA) of glioma patients in prior Radiation Therapy Oncology Group (RTOG) trials and compared with a matched standard population, as predicted by the model. PATIENTS AND METHODS: A total of 124 patients diagnosed with a GBM were treated with radiation therapy and intravenous tirapazamine between January 27,1995, and April 25,1997. All patients received 60 Gy in 2-Gy fractions. Tirapazamine was delivered three times a week for 12 treatments during radiotherapy. Fifty-five patients received tirapazamine at 159 mg/m2. A second dose level, 260 mg/m2, was opened, and 69 patients were entered. RESULTS: There was no significant survival advantage to the drug in any RPA class at either dose level. The median survival time was 10.8 months for the patient population treated with the 159-mg/m2 dose of tirapazamine and 9.5 months for the group treated with the 260-mg/m 2 dose of tirapazamine. Survival times by RPA class for patients receiving tirapazamine at 159 mg/m2 were 27.4 months (class III), 10.8 months (class IV), 7.9 months (class V), and 3.8 months (class VI). Survival times by RPA class for patients receiving tirapazamine at 260 mg/m2 were 16.2 months (class III), 10.3 months (class IV), 5.1 months (class V), and 1.3 months (class VI). Patients in RPA class III treated in the 159 mg/m2 dose arm had a notably longer survival than patients in the RTOG database RPA class III, but the difference did not reach statistical significance. There were no fatal toxicities. Grade 3/4 toxicities were more frequent at the higher dose level. CONCLUSION: Survival in the population treated with radiation and tirapazamine was equivalent to the control population. Patients in RPA class III treated with radiation and tirapazamine at the 159-mg/m2 dose had a longer survival when compared with the historical controls. The improvement in survival did not reach statistical significance. Toxicity was acceptable in both treatment arms, but grade 3/4 toxicities were more frequent in the higher dose regimen.
Prevention of Central Venous Catheter–Related Infections and Thrombotic Events in Immunocompromised Children by the Use of Vancomycin/Ciprofloxacin/Heparin Flush Solution: A Randomized, Multicenter, Double-Blind Trial
Authors: Henrickson Kelly J. , Axtell Richard A. , Hoover Susan M. , Kuhn Suzanne M. , Pritchett Jodi , Kehl Sue C. , Klein John P. 
Published: February 2017

PURPOSE: To determine whether an antibiotic flush solution containing vancomycin, heparin, and ciprofloxacin (VHC) can prevent the majority of line infections. PATIENTS AND METHODS: A prospective double-blind study was performed comparing VHC to vancomycin and heparin (VH) to heparin alone in 126 pediatric oncology patients. RESULTS: The 153 assessable lines resulted in 36,944 line days studied. There were 58 blood stream infections (43 Gram-positive, 14 Gram-negative, and one fungal). Forty were defined as line infections (31 heparin, three VH, six VHC). The time to develop a line infection was significantly increased using either antibiotic flush (VH, P = .011; VHC, P = .036). The rate of total line infections (VH, P = .004; VHC, P = .005), Gram-positive line infections (VH, P = .028; VHC, P = .022), and Gram-negative line infections (VH, P = .006; VHC, P = .003) was significantly reduced by either VH or VHC. Sixty-two (41%) of the lines developed 119 occlusion episodes (heparin, 3.99 per 1,000 line days; VHC, 1.75 per 1,000 line days; P = .0005). Neither antibiotic could be detected after flushing, and no adverse events were detected, including increased incidence of vancomycin-resistant Enterococcus colonization or disease. CONCLUSION: The use of either VH or VHC flush solution significantly decreased the complications associated with the use of tunneled central venous lines in immunocompromised children and would save significant health care resources.
Intensification With Intermediate-Dose Intravenous Methotrexate Is Effective Therapy for Children With Lower-Risk B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study
Authors: Mahoney Donald H. , Shuster Jonathan J. , Nitschke Ruprecht , Lauer Stephen , Steuber C. Philip , Camitta Bruce 
Published: February 2017

PURPOSE: To determine whether early intensification with 12 courses of intravenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 12 courses of IV MTX alone for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction therapy. Patients were randomized to receive intensification with IV MTX 1,000 mg/m2 plus IV MP 1,000 mg/m2 (regimen A) or IV MTX 1,000 mg/m2 alone (regimen C). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and triple intrathecal therapy every 12 weeks for 2 years. RESULTS: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The estimated 4-year overall continuous complete remission for patients treated with regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P = .5). No significant difference in overall outcome was shown by sex or race. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen. CONCLUSION: Intensification with 12 courses of IV MTX is an effective therapy for prevention of relapse in children with B-precursor ALL who are at lower risk for relapse but may be associated with an increased risk for neurotoxicity. Prolonged infusions of MP combined with IV MTX did not provide apparent advantage.
CD56 Expression Is an Indicator of Poor Clinical Outcome in Patients With Acute Promyelocytic Leukemia Treated With Simultaneous All-Trans-Retinoic Acid and Chemotherapy
Authors: Ferrara Felicetto , Morabito Fortunato , Martino Bruno , Specchia Giorgina , Liso Vincenzo , Nobile Francesco , Boccuni Piernicola , Di Noto Rosa , Pane Fabrizio , Annunziata Mario , Schiavone Ettore Mariano , De Simone Mariacarla , Guglielmi Cesare , Del Vecchio Luigi , Lo Coco Francesco 
Published: February 2017

PURPOSE: Preliminary reports suggest that leukemic cell expression of CD56, a neural cell adhesion molecule, is associated with adverse clinical outcome in either acute myeloid leukemia with t(8;21) or acute promyelocytic leukemia (APL). We investigated the prognostic relevance of CD56 in a series of patients with APL who were treated homogeneously with all-trans-retinoic acid (ATRA) and chemotherapy. PATIENTS AND METHODS: Clinicobiologic presenting features and therapeutic results were analyzed in a series of 100 patients with genetically proven APL who were treated, according to the example of the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto multicenter trial, with ATRA plus idarubicin (AIDA) and for whom data on CD56 expression were available at diagnosis. RESULTS: Fifteen patients (15%) showed expression of CD56 in greater than or equal to 20% blasts at diagnosis and were considered as CD56+. No differences were found regarding age, sex, WBC and platelet counts, incidence of coagulopathy, hemoglobin and fibrinogen levels, promyelocytic leukemia/retinoic acid receptor (PML/RAR) alpha fusion type, or complete remission (CR) rate in the comparison of the CD56+ and CD56− populations. Conversely, compared with patients who were CD56−, patients with CD56+ APL had shorter CR duration (P = .04) and overall survival (P = .002). In the multivariate analysis, CD56 positivity and initial WBC count greater than 10 × 109 cells/L retained statistical significance in overall survival (P = .04 and P = .02, respectively). CONCLUSION: The expression of CD56 is significantly associated with inferior CR duration and survival in patients with APL who were treated with modern frontline treatment that included ATRA and simultaneous chemotherapy. Combined with other well-established prognostic factors such as WBC count, CD56 expression at diagnosis might be used to build prognostic scores for risk-adapted therapy in APL.