bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor infusion makes high-dose etoposide a safe outpatient regimen that is effective in lymphoma and myeloma patients.
Authors: Gianni A M , Bregni M , Siena S , Magni M , Di Nicola M , Lombardi F , Tarella C , Pileri A , Bonadonna G 
Published: February 2017

PURPOSE This study assessed the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or recombinant human granulocyte colony-stimulating factor (rhG-CSF) in ameliorating the extent and duration of hematologic toxicity after high-dose etoposide cancer therapy. PATIENTS AND METHODS Thirty-two non-Hodgkin's lymphoma and myeloma patients were treated with 2 to 2.4 g/m2 etoposide infused intravenously (IV) during a 10- to 12-hour period, followed 72 hours later by subcutaneous administration of rhGM-CSF or rhG-CSF. Hematologic toxicity was compared with that observed in 29 patients who were treated with high-dose etoposide without growth factors. RESULTS The median duration of grade 4 neutropenia in growth factor-treated patients was 3 days, and granulocyte counts never decreased to less than 100/microL in approximately half of the patients. The corresponding figures in the control patients were 8 and 3 days, respectively (P < .0001). No effect was observed in platelet and RBC recovery. Growth factor-treated patients became eligible to receive additional myelotoxic chemotherapy a median of 5 days earlier than controls. Nonhematologic toxicity was minimal. Grade 1 mucositis was observed in two of 61 patients (3%). Antitumor activity assessed within 1 month after etoposide administration was documented in 58% of 38 assessable patients. Finally, high-dose etoposide expanded and mobilized the pool of peripheral-blood hematopoietic progenitors. CONCLUSION The use of rhGM-CSF or rhG-CSF makes high-dose etoposide a safe outpatient regimen and should encourage the inclusion of this highly effective and well-tolerated drug in novel treatment strategies that use high-dose therapy early in the clinical course of chemosensitive tumors.
Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia.
Authors: Copelan E A , Biggs J C , Avalos B R , Szer J , Cunningham I , Klein J P , Atkinson K , Kapoor N , Klein J L , Downs K 
Published: February 2017

PURPOSE The study was undertaken to investigate the effectiveness of allogeneic bone marrow transplantation from HLA-identical siblings after preparation with busulfan and cyclophosphamide in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Thirty-nine patients aged 15 to 42 years underwent transplantation at three different centers from November 1984 through November 1990. All patients received 16 mg/kg busulfan and 120 mg/kg cyclophosphamide as preparative therapy. Cyclosporine plus methotrexate or cyclosporine plus corticosteroids with or without methotrexate were given for prevention of graft-versus-host disease (GVHD). RESULTS Twelve patients died of treatment-related complications, 12 patients relapsed, and 15 patients are leukemia-free survivors. For 27 patients in group 1 (first remission, second remission, first relapse), the estimated leukemia-free survival (LFS) rate is 42.3% (95% confidence interval [CI], 22.9% to 71.7%) at 3 years. For 12 patients with more advanced disease (group 2), the 1-year LFS rate is 13.5% (95% CI, 0% to 37.1%). Chronic GVHD occurred at an estimated incidence of 63.3% and developed significantly more frequently among patients who received corticosteroids for prevention of acute GVHD. Chronic GVHD was associated with a significantly lower incidence of relapse and with improved LFS rates. CONCLUSION LFS rate in this study is comparable to that obtained with radiation-containing regimens; however, the effectiveness of this preparative regimen in ALL requires further study.
Long-term follow-up on National Cancer Institute Phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation.
Authors: Goffman T E , Dachowski L J , Bobo H , Oldfield E H , Steinberg S M , Cook J , Mitchell J B , Katz D , Smith R , Glatstein E 
Published: February 2017

PURPOSE We report the results of the final phase I/II program in glioblastoma (GBM) multiforme patients using only hyperfractionated irradiation and intravenous iododeoxyuridine (IdUrd). METHODS For a decade we investigated halogenated pyrimidine radiosensitizers in an effort to exploit the potential for differential uptake of thymidine analogs between proliferating tumor and normal brain tissues. Trials began with bromodeoxyuridine (BrdUrd) but were changed to IdUrd when the latter proved less photosensitizing. A series of dose-escalating pilot trials led to treatment at a maximum-tolerated dose (MTD) of IdUrd of 1,000 mg/m2/d for two separate 14-day courses, one during the initial radiation field and one during the cone down. The radiotherapy also evolved over time and was hyperfractionated in all cases reported. Over 5 years we accrued 45 patients into the final hyperfractionated, 1,000 mg/m2/d scheme. We report here results on only the patients with minimum follow-up of 1 year (90% had at least 2 years of follow-up) or until death. RESULTS The results do not indicate a significant benefit for use of sensitizers, as compared with other contemporary and aggressive types of radiation treatment. The median survival has been 11 months, with a 2-year actuarial survival of 9%. As yet, there are no survivors at 3 years. Tumor biopsies at craniotomy showed relatively low sensitizer incorporation. CONCLUSION The failure of radiosensitizers combined with radiation therapy to show major benefit may be due to patient selection but appears also to be related to the combined problems of poor drug penetration/uptake into tumor, tumor-cell heterogeneity, and a high inherent cellular radioresistance of GBM.
Tamoxifen and the isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients.
Authors: Osborne C K , Wiebe V J , McGuire W L , Ciocca D R , DeGregorio M W 
Published: February 2017

PURPOSE The antiestrogen tamoxifen is effective in therapy for breast cancer. However, its use is limited by the eventual development of acquired tamoxifen resistance in many patients. The mechanisms responsible for tamoxifen resistance remain unknown; loss of estrogen receptor (ER), selection of hormone-independent breast cancer clones, or alterations in serum tamoxifen levels after long-term use do not explain acquired resistance in most patients. Using an experimental model in which human breast cancer cells develop resistance in athymic mice treated with tamoxifen, we have recently shown that acquired resistance is associated with markedly reduced cellular concentrations of tamoxifen and by isomerization of the trans-4-hydroxy metabolite to the less potent cis isomer. MATERIALS AND METHODS Using a sensitive high-performance liquid chromatography (HPLC) assay, we have now measured levels of tamoxifen and its major metabolites in a series of 14 tumors from patients treated with tamoxifen. The duration of therapy ranged from 1 month to 6 years. RESULTS Tumor tamoxifen levels varied over a wide range. Low concentrations were observed in tumors from eight patients, all demonstrating progressive disease at the time of biopsy after a minimum duration of treatment of 6 months. Six tumors had moderate to high tamoxifen levels, two from patients responding to tamoxifen, one from a patient with stable disease, and three from patients with disease progression. Both the cis and trans isomers of the potent antiestrogenic metabolite 4-hydroxy-tamoxifen were detected in 11 tumors. Six tumors had high ratios of the cis to trans isomer (1.10:2.06), all from patients not responding to tamoxifen. The five tumors with low cis:trans ratios included the two tumors from responding patients and three from patients with progression. All but one of the 11 nonresponding patients had either a low tumor tamoxifen level, a high cis:trans ratio, or both. CONCLUSION This study clearly demonstrates a wide range of tumor tamoxifen levels and accumulation of the less antiestrogenic cis isomer of 4-hydroxytamoxifen in some patients on tamoxifen therapy. Additional study is necessary to determine if these metabolic profiles are related to the development of tamoxifen resistance.
A population-based study of neuroblastoma incidence, survival, and mortality in North America.
Authors: Bernstein M L , Leclerc J M , Bunin G , Brisson L , Robison L , Shuster J , Byrne T , Gregory D , Hill G , Dougherty G 
Published: February 2017

PURPOSE The purpose of this study was twofold: (1) to provide a population-based estimate of neuroblastoma incidence, disease stage and age distribution, and survival and mortality rates in North America; and (2) to compare these figures in the province of Quebec at a time shortly before the institution of province-wide screening with those in a population-based control group, the Greater Delaware Valley (GDV) Pediatric Tumor Registry. MATERIALS AND METHODS In Quebec, the four major pediatric teaching hospital records were searched for children with a diagnosis of neuroblastoma. Tumor board registry data and information supplied to the Division of Vital Statistics were also reviewed. Birth statistics were obtained from the population registry. The GDV Pediatric Tumor Registry is a population-based registry of pediatric cancer covering all of Delaware and parts of New Jersey, Pennsylvania, and Maryland. Age, stage of disease, and follow-up data were obtained through December 31, 1989, with Evans neuroblastoma staging data used for all comparisons. RESULTS One hundred thirty children with neuroblastoma were identified in Quebec and 165 in the GDV, in a combined population of 3,178,736 children. The annual incidence of neuroblastoma was 10.95/10(6) under the age of 15 years and 27.75/10(6) between the ages of 0 and 4 years. The annual mortality rate due to neuroblastoma was 4.89/10(6) and 9.10/10(6) for the age groups 0 to 14 and 0 to 4, respectively. The overall 10-year survival rate for the 295 cases of neuroblastoma was 55%. The 10-year survival rates for patients with Evans stage I-IV and IVS disease were 88%, 90%, 63%, 21%, and 81%. There was no significant difference observed in the incidence, mortality, or survival in the two populations. CONCLUSION These data represent the first large, population-based description of the clinical presentation and outcome of patients with neuroblastoma in North America, with no significant differences noted between Quebec patients and the GDV patients.
2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia.
Authors: Santana V M , Mirro J , Kearns C , Schell M J , Crom W , Blakley R L 
Published: February 2017

PURPOSE The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and showed promising anti-leukemic activity in a phase I trial conducted at St Jude Children's Research Hospital. To substantiate and extend this result, we performed a phase II trial in a representative group of children and young adults with relapsed acute leukemia. PATIENTS AND METHODS Twenty-four patients (median age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual blast cells 10 days after treatment received a second course of 2-CDA that was identical to the first. Detailed pharmacokinetic studies were performed on plasma collected from five patients. RESULTS Eight (47%) of the 17 patients with AML had complete hematologic remissions (four after the initial course of 2-CDA), and two (12%) had partial remissions, for a total response rate of 59%. Only one child with ALL achieved remission. Seven of the responding patients underwent allogeneic or autologous bone marrow transplantation, with six remaining free of leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug-induced toxicity was hematologic, with severe neutropenia and thrombocytopenia (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses of 2-CDA. In responding patients, the median times to recovery of neutrophil counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54 nmol/L). CONCLUSION 2-CDA given by prolonged continuous infusion has clinically significant activity against AML and merits further testing in multidrug regimens for this disease.
Treatment of chronic myelogenous leukemia in accelerated and blastic phases with daunorubicin, high-dose cytarabine, and granulocyte-macrophage colony-stimulating factor.
Authors: Kantarjian H M , Talpaz M , Kontoyiannis D , Gutterman J , Keating M J , Estey E H , O'Brien S , Rios M B , Beran M , Deisseroth A 
Published: February 2017

PURPOSE The study was undertaken to improve the results of intensive chemotherapy in chronic myelogenous leukemia (CML) in accelerated (CML-AP) and blastic phases (CML-BP) by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) as supportive therapy. PATIENTS AND METHODS Forty-eight patients were treated with daunorubicin 120 mg/m2 intravenously on day 1, cytarabine (ara-C) 1.5 g/m2/d by continuous infusion over 24 hours for 4 days, and Solu-Medrol (methylprednisolone; The Upjohn Co, Kalamazoo, MI) 100 mg/d for 5 days, followed on day 5 by GM-CSF 125 micrograms/m2/d over 6 hours until recovery of granulocyte count above 2.0 x 10(3)/microliters. Twenty-four patients had CML-BP, and 24 had CML-AP. RESULTS During remission induction, 45 patients (94%) developed febrile episodes (fever of unknown origin, 23 patients [48%]; documented infections, 22 patients [46%]). The median time to recovery of granulocyte count above 0.5 x 10(3)/microliters was 29 days and to platelet count above 30 x 10(3)/microliters, 28 days. Overall, 14 of 48 patients (29%) achieved a complete hematologic remission (CHR), and seven (15%) reverted to a second chronic phase. CHR was noted in eight of 24 patients with CML-BP (33%), and in six of 24 patients with CML-AP (25%). Cytogenetic responses were observed in 11 patients (23%), but were transient. Sixteen patients developed either fluid retention, hypotension, pleuropericardial effusions, or pericarditis, or a combination of these side effects. These side effects were severe in four patients and are likely to be disease-associated, as a similar regimen of intensive chemotherapy and GM-CSF at the same dose and schedule in acute lymphocytic leukemia was not associated with these side effects. CONCLUSIONS The results pertinent to remission rates, induction mortality, myelosuppression profile and related complications, and overall survival were not significantly improved compared with previous experience. In summary, the results of intensive chemotherapy in CML-transformed phases remain poor, despite the addition of GM-CSF as a supportive measure.
Carboplatin: an active drug in metastatic breast cancer.
Authors: Martín M , Díaz-Rubio E , Casado A , Santabárbara P , López Vega J M , Adrover E , Lenaz L 
Published: February 2017

PURPOSE The study was undertaken to assess the antitumor activity of carboplatin 400 mg/m2 intravenously every 4 weeks in metastatic breast cancer (MBC). PATIENTS AND METHODS Thirty-four MBC patients without any prior exposure to chemotherapy entered the study. All patients had measurable disease in at least one site and were assessable for response and toxicity. RESULTS Of 34 assessable patients, 12 obtained a complete (one) or partial (11) response to carboplatin, resulting in an overall response rate of 35% (95% confidence interval, 19.8% to 53.5%). The median duration of response was 8 months (range, 2+ to 12 months). Responses were seen in lymph nodes (four of six), lung (five of nine), skin and soft tissues (four of nine), breast (two of eight), and liver (three of 11), but not in measurable lytic lesions of the bone. Toxicity was mild, mainly consisting of emesis (81% of the patients; 66% of the courses), leukopenia of World Health Organization (WHO) grade 1 to 2 (47% of the patients; 18% of the courses), and thrombocytopenia (12% of the patients; 3% of the courses). There were no cases of life-threatening toxicity, although one patient developed grade 4 thrombocytopenia without bleeding. Of 22 patients who did not respond to carboplatin, 18 received salvage therapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF; 15 patients); cyclophosphamide, methotrexate, and fluorouracil (CMF; one patient); or hormones (two patients). Objective responses to CAF and hormonal therapy were seen in 11 of 15 and two of two patients, respectively. The remaining patient did not respond to CMF salvage chemotherapy. Overall, the response rate to either first-line carboplatin or second-line salvage therapy was 73.5% (25 of 34 patients). After a median follow-up time of 22 months, the median survival was 19 months. CONCLUSIONS Carboplatin is an active drug in MBC patients without previous exposure to chemotherapy. In our study, the use of an experimental drug as first-line single-agent treatment in MBC did not have a negative influence on patient survival, as the majority of the carboplatin nonresponding patients could be salvaged with a conventional therapeutic regimen.
Identification of patients who are at high risk for locoregional breast cancer recurrence after conservative surgery and radiotherapy: a review article for surgeons, pathologists, and radiation and medical oncologists.
Authors: Clarke D H , Martinez A A 
Published: February 2017

PURPOSE Many retrospective reports have been published identifying risk factors for locoregional (LR) recurrence after breast conservation therapy (BCT). We review these reports, with the purpose of better enabling surgeons, pathologists, radiation oncologists, and medical oncologists to develop strategies for an individualized treatment approach. DESIGN AND RESULTS English-language retrospective and prospective randomized studies published in the 1980s were reviewed. Histopathologic predictors, young age, extent of conservative surgery (CS), lobular carcinoma, and the impact of adjuvant chemotherapy are all examined as reported risk factors for LR. CONCLUSIONS Recognition of these factors provides rationale for individualizing the extent of CS based on histopathologic features. In addition, the aggressiveness of radiotherapy (RT) should be dictated by the extent of CS and by identifiable prognostic factors. Strategies are presented for an individualized treatment approach based on a clear understanding of the prognostic factors for LR.
Etoposide, doxorubicin, and cisplatin chemotherapy for advanced gastric adenocarcinoma: results of a phase II trial.
Authors: Lerner A , Gonin R , Steele G D , Mayer R J 
Published: February 2017

PURPOSE A phase II study of etoposide, doxorubicin, and cisplatin (EAP) therapy in patients with advanced gastric carcinoma was performed in an attempt to confirm encouraging results reported by German investigators using an identical EAP regimen. PATIENTS AND METHODS Thirty-six consecutive, previously untreated patients with surgically unresectable, measurable gastric carcinoma were treated every 28 days with etoposide (120 mg/m2, days 4, 5, and 6), doxorubicin (20 mg/m2, days 1 and 7), and cisplatin (40 mg/m2, days 2 and 8). A total of 108 courses of treatment was given. RESULTS Therapy was associated with myelosuppression (median granulocyte nadir, 239/microL; median platelet nadir, 81,000/microL), which reached its maximum 14 days after the start of therapy and necessitated hospitalization after 24 of 108 (22%) treatment courses. Four of 36 (11%) patients died of treatment-related toxicity: three from sepsis and one from hemorrhage. Objective responses were observed in 12 of 36 (33%) patients; three (8%) patients experienced a clinical complete response. The median time to progression was 4 months for all 36 patients and 8 months for the 12 responding patients. Of the 13 patients with localized but unresectable disease, five subsequently underwent surgical resection; only one of these five was rendered disease-free. CONCLUSION The EAP regimen is highly toxic and results in response rates and survival times no better than those of more easily tolerated treatment programs.
Is postchemotherapy retroperitoneal surgery necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses?
Authors: Fosså S D , Qvist H , Stenwig A E , Lien H H , Ous S , Giercksky K E 
Published: February 2017

PURPOSE At least one third of the patients with metastatic testicular cancer are rendered tumor-free by cisplatin-based chemotherapy. One may question, therefore, the routine use of postchemotherapy retroperitoneal lymph node dissection (RLND), especially if the residual masses are less than 20 mm in diameter. To define the role of such surgery, we analyzed the postchemotherapy histology in testicular cancer patients with minimal residual disease. PATIENTS AND METHODS Seventy-eight patients with advanced nonseminomatous testicular cancer underwent RLND after three to four cycles of cisplatin- or carboplatin-based chemotherapy. In all patients, the largest diameter of the residual retroperitoneal mass was less than 20 mm. RESULTS Complete fibrosis/necrosis was found in 51 patients, mature teratoma in 22, and vital malignant germ cell tumor in five. In two of the latter five patients, alphafetoprotein (AFP) had increased immediately before RLND. In the 76 patients with normal pre-RLND tumor markers, the presence of undifferentiated malignant teratoma (MTU) in the primary tumor and normal prechemotherapy tumor markers were independent parameters predicting complete fibrosis/necrosis, which was demonstrated in all 15 patients with these two pretreatment parameters. CONCLUSIONS Postchemotherapy RLND can be omitted in patients with MTU in the primary tumor who have normal AFP/human chorionic gonadotropin (AFP/HCG) before chemotherapy and whose residual retroperitoneal mass is less than 20 mm in diameter. If the pre-RLND tumor markers are normal, RLND should be performed in all other patients with small residual masses, even in the presence of a normal computed tomography (CT) and particularly if regular follow-up of the patients is not guaranteed.