bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double dose-intensive chemotherapy with autologous stem-cell support for metastatic breast cancer: no improvement in progression-free survival by the sequence of high-dose melphalan followed by cyclophosphamide, thiotepa, and carboplatin.
Authors: Ayash L J , Elias A , Schwartz G , Wheeler C , Ibrahim J , Teicher B A , Reich E , Warren D , Lynch C , Richardson P , Schnipper L , Frei E , Antman K 
Published: February 2017

PURPOSE Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/ m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration. METHODS Women with at least partial responses (PRS) to induction received melphalan (140 or 180 mg/ m2) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival times for the whole group are estimated at 11 and 20 months, respectively. CONCLUSION Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agenting that may adversely influence outcome.
Improving the cancer chemotherapy use process.
Authors: Fischer D S , Alfano S , Knobf M T , Donovan C , Beaulieu N 
Published: February 2017

PURPOSE Reports of the tragic consequences of erroneous cancer chemotherapy overdoses at a prominent cancer center and a university hospital prompted a review of our institution's practices and those of 123 other hospitals to ascertain for each the current in-house process to prevent chemotherapy errors. METHODS A multidisciplinary committee of oncologists, nurses, and pharmacists reviewed the chemotherapy use process and identified opportunities for improvement. A 1-page facsimile survey was answered by 150 of 215 members of the American Society of Clinical Oncology (ASCO) who received it. RESULTS We further restricted the writing of cytotoxic chemotherapy orders to physicians who were board-certified or -eligible in hematology or medical, pediatric, and gynecologic oncology and their approved fellows. Dispensation of drugs is limited to oncology-certified pharmacists, and administration to chemotherapy-certified nurses. Standard orders are used either on special oncology forms or designated order sets in the computer. Procedures to regulate the ordering of antineoplastic drugs for nonmalignant indications by nononcology specialists are outlined. A process to prevent chemotherapy errors is in place in 95% of hospitals. Dedicated medical oncology units are ubiquitous, and most cancer centers and university hospitals have dedicated gynecologic and pediatric oncology units. Chemotherapy orders are generally written by oncology fellows and countersigned by an attending oncologist in cancer centers and university hospitals, whereas private oncology attending physicians write them in most community hospitals. Drugs are administered by oncology-certified nurses in most institutions. CONCLUSIONS These recommendations should improve the safety and effective use of chemotherapy and reduce the error rate to as close to zero as human fallibility will allow.
Treatment of cancer with radiation and drugs.
Authors: Tannock I F 
Published: February 2017

PURPOSE To review the current status and future prospects of combined treatment of cancer with radiation and drugs. DESIGN A review of (1) mechanisms whereby combined use of radiation and drugs might lead to improved therapeutic benefit for the treatment of cancer; (2) problems related to the design and analysis of clinical trials that evaluate combined modality treatment; and (3) clinical results of larger randomized trials that have compared combined versus single modality treatment for various types of cancer. RESULTS Improvement in the therapeutic index depends on exploitation of the biologic properties that differ between tumors and normal tissues; such properties may include mechanisms of resistance to radiation and drugs, tissue microenvironment, and cell proliferation or repopulation during radiotherapy. To detect or rule out the small but clinically important differences in outcome that might occur will require the performance of large, randomized, controlled trials or patient-based meta-analyses; single-arm studies, small randomized trials, and subgroup analyses of larger trials can generate hypotheses. Clinical gains from combined treatment have been demonstrated in a few sites, with disappointing results in others. In general, more promising results have accrued from concurrent treatment, despite greater toxicity, than from sequential use of drugs and radiation. CONCLUSION Clinical gains from combined treatment with radiation and drugs have been small. New, mechanistically based approaches to combined treatment are required.
Phase I/II trial of PIXY321 to enhance engraftment following autologous bone marrow transplantation for lymphoid malignancy.
Authors: Vose J M , Anderson J E , Bierman P J , Appelbaum F R , Anderson J R , Garrison L , Lebsack M E , Armitage J O 
Published: February 2017

PURPOSE A phase I/II study of PIXY321 following high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) was conducted to evaluate the safety and clinical potential of this agent. PATIENTS AND METHODS Fifty patients with Hodgkin's disease or non-Hodgkin's lymphoma (NHL) undergoing HDT and ABMT received PIXY321 post-ABMT in doses that ranged from 50 to 1,000 micrograms/m2/d either as intravenous (i.v.) or subcutaneous (SC) dosing until engraftment was reached. RESULTS If all doses are considered together, the median time to reach an absolute neutrophil count (ANC) > or = 500/microL was 18 days and the median time to platelet transfusion independence was 21 days. At the estimated optimum dose of 750 micrograms/m2/d by SC injection once daily, the median time to reach an ANC > or = 500/microL was 15 days and the median time to platelet transfusion independence was 16 days. Historical control patients who received granulocyte-macrophage colony-stimulating factor (GM-CSF) had a median time to an ANC > or = 500/microL of 19 days and a median time to platelet independence of 26 days. CONCLUSION The administration of PIXY321 post-ABMT was generally well tolerated and resulted in prompt engraftment in the majority of patients who underwent HDT and ABMT for lymphoid malignancies. The optimum dose and route of administration of PIXY321 suggested by this trial was 750 micrograms/m2/d by once-daily SC injection. Compared with historical control patients who received 2-hour i.v. GM-CSF, patients who received PIXY321 at 750 micrograms/m2/d by SC injection once daily had an improvement in the median days to neutrophil and platelet engraftment by 4 and 10 days, respectively.
Significance of cytogenetic findings for the clinical outcome in patients with T-cell lymphoma of angioimmunoblastic lymphadenopathy type.
Authors: Schlegelberger B , Zwingers T , Hohenadel K , Henne-Bruns D , Schmitz N , Haferlach T , Tirier C , Bartels H , Sonnen R , Kuse R 
Published: February 2017

PURPOSE The aim of this study was to evaluate the significance of cytogenetic findings for the clinical outcome of patients with Angioimmunoblastic Lymphadenopathy (AILD)-Type T-cell lymphoma. MATERIALS AND METHODS In a retrospective analysis, the cytogenetic findings of 50 patients with AILD-type T-cell lymphoma were correlated with the frequency of spontaneous and therapy-induced remissions and with survival using the statistical methods of Kaplan and Meier and the model of Cox for multivariate analysis. Treatment was not uniform because the patients were treated in different hospitals during a period of 8 years and because a standard therapy has not yet been established. RESULTS The following cytogenetic findings were associated with a significantly lower incidence of therapy-induced remissions and a significantly shorter survival duration: presence of aberrant metaphases in unstimulated cultures (P = .04 for both parameters); clones with an additional X chromosome (P = .0001 and P = .03, respectively); structural aberrations of the short arm of chromosome 1, preferentially involving 1p31-32 (P < .001 and P = .04, respectively); and complex aberrant clones with more than four aberrations (P = .0003 and P = .005, respectively). Multivariate analysis showed that these cytogenetic findings had a significant influence on survival, but therapy modalities did not. Only the presence of complex aberrant clones was an independent prognostic factor. Trisomy 3 had no effect on survival, but patients without trisomy 5 (P = .08) tended to live longer. CONCLUSION This is the first study that seems to indicate that cytogenetic findings have prognostic significance in AILD-type T-cell lymphoma. These results must be proven in prospective studies of homogeneously treated patients.
Inferior vena cava filters in cancer patients: indications and outcome.
Authors: Schwarz R E , Marrero A M , Conlon K C , Burt M 
Published: February 2017

PURPOSE Our experience with inferior vena cava (IVC) filter placement to prevent pulmonary emboli (PE) in cancer patients with deep vein thromboses (DVT) was reviewed to identify indications, patient characteristics, complications, and long-term outcome. METHODS Charts of 182 patients with cancer were retrospectively analyzed. All patients had received an IVC filter in our institution between January 1980 and April 1992. RESULTS Of 182 patients, 103 were men and 79 were women. Median age was 59 years (range, 15 to 88). Eight patients (4%) had stage I disease, 22 patients (12%) stage II, 37 patients (20%) stage III, and 115 patients (63%) stage IV. A DVT was diagnosed in 97 patients (53%), a PE in 46 patients (25%), and a combination in 39 patients (21%). Indications for IVC filter placement were DVT or PE in the presence of contraindications to anticoagulation therapy (perioperative, n = 58; CNS metastases, n = 20; thrombocytopenia, n = 7; bleeding, n = 61; others, n = 24; total, N = 170) or anticoagulation failure (recurrent PE, n = 6; recurrent DVT; n = 6; total N = 12). Filter placement complications (n = 6, 3%) included malposition (n = 3), migration (n = 1), arrhythmia (n = 1), and wound infection (n = 1), but no deaths. After filter placement, four patients developed a recurrent PE, and 11 patients developed a recurrent DVT. No significant postthrombotic complications were observed. CONCLUSION IVC filter placement patients with advanced cancer and thrombotic complications is safe, well tolerated, and can offer effective therapy/prophylaxis with a low incidence of treatment failure.
Tamoxifen-associated eye disease. A review.
Authors: Nayfield S G , Gorin M B 
Published: February 2017

PURPOSE The oral antiestrogen tamoxifen has demonstrated efficacy in the treatment of metastatic breast cancer and as adjuvant therapy in early-stage disease. Clinical trials of tamoxifen in chemoprevention of breast cancer among high-risk women have focused attention on potential adverse effects of long-term tamoxifen use, including the possibility of ocular toxicity. This review evaluates the published case reports, clinical series, and clinical trial data on ocular toxicities attributed to tamoxifen. Clinical issues of surveillance, differential diagnosis, and management of tamoxifen-related eye disease are discussed. DESIGN National Library of Medicine online bibliographic services were used to identify case reports and clinical studies of ocular adverse effects that occurred in patients receiving tamoxifen published through the fall of 1994. The medical literature relevant to issues raised by the reports and studies was similarly identified and reviewed. RESULTS Case reports and case series identify crystalline retinal deposits, macular edema, and corneal changes as potential tamoxifen ocular toxicities. Extensive retinal lesions and macular edema with visual impairment have been reported in a few patients receiving high-dose tamoxifen. Less extensive retinal changes may occur in patients receiving low doses for long periods, and isolated retinal crystals may be observed in patients without visual symptoms. CONCLUSION Ocular toxicity is uncommon in the current clinical setting of long-term, low-dose tamoxifen use. Physicians should be aware of the potential for ocular toxicity among patients receiving the drug and should assure appropriate surveillance and prompt evaluation of visual complaints.
Phase I and pharmacologic study of sequences of paclitaxel and cyclophosphamide supported by granulocyte colony-stimulating factor in women with previously treated metastatic breast cancer.
Authors: Kennedy M J , Zahurak M L , Donehower R C , Noe D A , Sartorius S , Chen T L , Bowling K , Rowinsky E K 
Published: February 2017

PURPOSE Pacltaxel is active in metastatic breast cancer, but limited information is available on combinations of this agent with other cytotoxic agents. Study aims were to determine the maximum-tolerated doses (MTDs) of paclitaxel (24-hour infusion) and cyclophosphamide (1-hour infusion) administered every 21 days with granulocyte colony-stimulating factor (G-CSF, filgrastim) to determine the effect of drug sequence on toxicity and pharmacology and to evaluate the activity of this combination in women with anthracycline-resistant disease. PATIENTS AND METHODS Thirty-seven women with metastatic breast cancer were treated. Starting doses were paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2, with filgrastim 5 microG/kg/d subcutaneously beginning 24 hours after chemotherapy. Four patients were treated at each dose level. The sequence of drug administration was alternated between sequential patients, and with subsequent courses of therapy in each patient, to enable evaluation of effects of drug sequence on toxicity and pharmacology. Patients were treated every 21 days and disease status was reevaluated every two courses. RESULTS Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 is the MTD for this combination on this schedule. The hematopoietic toxicity of therapy was sequence-dependent. Paired analysis of toxicity data indicated more severe toxicity in courses in which paclitaxel was administered first. Sequence-dependent pharmacologic effects did not account for this phenomenon. Responses were noted in 29% of patients with anthracycline-resistant disease. CONCLUSION Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 with filgrastim administered every 21 days are the doses recommended for further study.
Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study.
Authors: McGuire W P , Blessing J A , Moore D , Lentz S S , Photopulos G 
Published: February 2017

PURPOSE Taxol (paclitaxel; Bristol-Myers Squibb, Princeton, NJ) is a new antineoplastic drug with broad-spectrum activity in solid tumors, including epithelial ovarian cancer, head and neck cancer, esophageal cancer, breast cancer, bladder cancer, and lung cancer. Its unique mechanism of action, polymerization of tubulin monomers, has stimulated both clinical and preclinical research on this agent. As limited drug supplies became more plentiful, a phase II trial of Taxol was initiated in patients with advanced squamous cervix cancer who had received no prior chemotherapy. PATIENTS AND METHODS In this trial, 30 assessable patients were initially entered onto the study and four partial responses were seen. Further accrual of 22 assessable patients was then accomplished to define better the response rate with smaller confidence intervals. The starting dose of Taxol was 170 mg/m2 (135 mg/m2 for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalations to 200 mg/m2 and deescalations to 110 mg/m2 were allowed based on adverse effects. RESULTS The final response rate was 17% (two complete responses and seven partial responses). The primary and dose-limiting toxicity was neutropenia. CONCLUSION The response rate makes Taxol a drug with sufficient activity to explore it in combination with other agents with similar activity.
Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.
Authors: Stahl M , Wilke H , Fink U , Stuschke M , Walz M K , Siewert J R , Molls M , Fett W , Makoski H B , Breuer N , Schmidt U , Niebel W , Sack H , Eigler F W , Seeber S 
Published: February 2017

PURPOSE The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC. PATIENTS AND METHODS Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation. RESULTS Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively. CONCLUSION This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.
High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group.
Authors: Veerman A J , Hählen K , Kamps W A , Van Leeuwen E F , De Vaan G A , Solbu G , Suciu S , Van Wering E R , Van der Does-Van der Berg A 
Published: February 2017

PURPOSE Here we report the results of a nationwide cooperative study in the Netherlands on acute lymphoblastic leukemia (ALL) in children. The aim of the study was to improve the cure rate and to minimize side effects in a group of non-high-risk ALL patients, especially with regard to the CNS. A second aim was to study potential prognostic factors. METHODS Children (age 0 to 15 years) with non-high-risk ALL (WBC count < 50 x 10(9)/L, no mediastinal mass, no B-cell phenotype, and no CNS involvement) were treated with a uniform protocol, ALL VI. The treatment protocol used 6-week induction regimen with three drugs (vincristine, dexamethasone, and asparaginase), three weekly doses of intravenous (IV) medium high-dose methotrexate (2 g/m2), and 2-year maintenance therapy that consisted of alternating 5-week periods of methotrexate and mercaptopurine and 2-week periods of vincristine and dexamethasone. In the first year of maintenance, triple intrathecal therapy was administered every 7 weeks. RESULTS From December 1, 1984 until July 1, 1988, 291 children with ALL were diagnosed; 206 were categorized as non-high-risk (71%), and 190 were treated according to protocol ALL VI. At 8 years, the event-free survival (EFS) rate was 81% (SE = 3%) and survival rate 85% (SE = 2.9%); the median follow-up time was 7.3 years (range, 36 to 117 months). The CNS relapse rate was 1.1% (two of 184 patients who achieved a complete remission [CR]). The only factor found to be of negative prognostic importance in terms of EFS (P = .05) was a positive acid phosphatase reaction. CONCLUSION For children with non-high-risk ALL, the combination of IV medium high-dose methotrexate (2 g/m2 times three), triple intrathecal therapy in the first year of maintenance treatment, and the use of dexamethasone for induction and pulses during maintenance treatment has proved to be highly effective, especially in the prevention of CNS relapse. A high cure rate was achieved without the use of anthracyclines, alkylating agents, and cranial irradiation.
Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen.
Authors: Magrath I , Adde M , Shad A , Venzon D , Seibel N , Gootenberg J , Neely J , Arndt C , Nieder M , Jaffe E , Wittes R A , Horak I D 
Published: February 2017

PURPOSE We have used identical treatment protocols for adults and children with small non-cleaved-cell lymphoma (SNCL) for many years and report here the results of two successive treatment regimens in these age groups. PATIENTS AND METHODS Seventy-two patients (39 adults and 33 children) were treated with protocol 77-04 between 1977 and 1985. All patients, except those with resected abdominal disease, received 15 cycles of a combination of cyclophosphamide (CTX), doxorubicin (ADR), prednisone (PRED), vincristine (VCR), high-dose methotrexate (MTX), and intrathecal (IT) therapy. Forty-one patients (20 adults and 21 children) were treated with protocol 89-C-41, which has been used since 1989. High-risk patients received four alternating cycles (with a total duration of 12 to 15 weeks) of an intensified version of protocol 77-04 without PRED (CODOX-M), and a new drug combination consisting of ifosfamide, etoposide, high-dose cytarabine (ara-C), and IT MTX (IVAC). Low-risk patients received three cycles of the CODOX-M regimen. High-risk patients were randomized to either receive or not receive granulocyte-macrophage colony-stimulating factor (GM-CSF). RESULTS Event-free survival (EFS) in protocol 77-04 was 56% at 2 years and beyond. EFS in protocol 89-C-41 was 92% at 2 years and beyond. GM-CSF was associated with increased thrombocytopenia. CONCLUSION Adults and children with SNCL have a similar prognosis when treated with the same chemotherapy. EFS in high-risk patients has been markedly improved by including IVAC in protocol 89-C-41, and excellent results can be achieved with only four cycles of therapy. In protocol 89-C-41, GM-CSF was not beneficial.