tbuckley/cabot-search huggingface dataset:
Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d'Etude de la Greffe de Moelle Osseuse.
Authors: P Bordigoni, J P Vernant, G Souillet, E Gluckman, D Marininchi, N Milpied, A Fischer, E Benz Lemoine, J P Jouet, J Reiffers
Journal: Journal of Clinical Oncology (1989)

Thirty-two children ranging in age from 1.5 to 16 years with poor-prognosis acute lymphoblastic leukemia (ALL) were treated with myeloablative immunosuppressive therapy consisting of cyclophosphamide (CPM) and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) while in first complete remission (CR). The main reasons for assignment to BMT were WBC count greater than 100,000/microL, structural chromosomal abnormalities, and resistance to initial induction therapy. All children were transplanted with marrow from histocompatible siblings. Twenty-seven patients are alive in first CR for 7 to 82 months post-transplantation (median, 30 months). The actuarial disease-free survival rate is 84.4% (confidence interval, 7.2% to 29%) and the actuarial relapse rate is 3.5% (confidence interval, 0.9% to 13%). Four patients died of transplant-related complications, 16 developed low-grade acute graft-v-host disease (GVHD), and six developed chronic GVHD. The very low incidence of relapse (one of 28 long-term survivors) precluded the determination of the prognostic significance of the different poor-outcome features. Moreover, two infants treated with busulfan, CPM, and cytarabine (Ara-C) relapsed promptly in the marrow. In summary, as a means of providing long-term disease-free survival and possible cure, BMT should be considered for children with ALL presenting poor-prognostic features, particularly certain chromosomal translocations [t(4;11), t(9;22)], very high WBC counts, notably if associated with a non-T immunophenotype, and, perhaps, a poor response to initial therapy with corticosteroids (CS), or infants less than 6 months of age.
Do 5-hydroxytryptamine<sub>3</sub> receptor antagonists (5-HT<sub>3</sub>) improve the antiemetic effect of dexamethasone for preventing delayed chemotherapy-induced nausea and vomiting (CINV)? A meta-analysis of randomized controlled trials
Authors: J. Q. Huang, G. F. Zheng, R. Deuson, Y. Briand, G. C. F. Chan, J. Karlberg, B. C. Y. Wong
Journal: Journal of Clinical Oncology (2004)

6037 Background: 5-HT3 receptor antagonists combined with dexamethasone are commonly used to control delayed CINV, despite the lack of supporting evidence from randomized clinical trials. We aimed to evaluate systematically if adding a 5-HT3 receptor antagonist to dexamethasone (combination therapy) is more effective than dexamethasone alone for preventing delayed CINV. Methods: We undertook a meta-analysis of studies that met the following criteria: randomized clinical trials comparing the efficacy of the combination therapy versus dexamethasone alone for preventing delayed CINV; same prophylactic treatment for acute CINV must be used. Studies without raw data or duplicate publications were excluded. A comprehensive literature search was conducted to October 2003 in Medline, PubMed, Embase, CANCERLIT and Cochrane Databases, supplemented by a hand search of reference lists, relevant meeting abstracts and journals. Results: Of 50 potentially useful studies, 5 reports involving 1997 patients that met the predefined entry criteria were included. The overall total protection (no nausea, no vomiting, any / or without rescue medications) from delayed CINV was similar between patients receiving the combination therapy (53.2%, 454/853) and dexamethasone alone (53.3%, 450/844), yielding a relative risk (RR) of 1.03 [95% confidence interval (CI) 0.97–1.09]. Similar efficacy between the two treatment groups was also observed for preventing delayed nausea [RR 1.03 (95% CI 0.98–1.09)] and delayed vomiting [RR 1.03 (95% CI 0.99–1.07)]. Conclusions: Adding a 5-HT3 receptor antagonist to dexamethasone does not improve the antiemetic effect of dexamethasone for preventing delayed CINV. The current recommendation of using this combination treatment for controlling delayed CINV warrants evidence-based re-evaluation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck & Co., Inc.; Merck, Sharpe & Dohme, France Merck & Co. Inc
A phase II trial of pemetrexed (P), gemcitabine (G), and bevacizumab (BV) in untreated patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: A. J. Wozniak, G. P. Kalemkerian, S. M. Gadgeel, B. J. Schneider, M. Valdivieso, R. Venkatramanamoorthy, D. M. Hackstock, W. Chen, L. K. Heilbrun, J. D. Ruckdeschel
Journal: Journal of Clinical Oncology (2009)

e19099 Background: P and G are active agents with acceptable toxicity profiles in the treatment of NSCLC. The addition of BV to chemotherapy has resulted in a significant improvement in survival for pts with non-squamous NSCLC. We are currently conducting a phase II trial of P, G and BV on a novel every two week schedule in untreated pts with advanced NSCLC. Methods: Advanced, non-squamous NSCLC pts with measurable/evaluable disease, no prior treatment for advanced disease, PS 0–1, adequate hepatic, renal and bone marrow function, treated brain metastases were eligible. No unstable hypertension/cardiac disease/vascular disease, hemoptysis, anti-coagulation, recent major surgery, no cavitation or close proximity of primary cancer to a major vessel were allowed. Pts received P 500 mg/m 2 , G 1,500 mg/m 2 , and BV 10 mg/kg every 2 weeks for 12 cycles. Doses were reduced to P 400 mg/m 2 and G 1,200 mg/m 2 when grade 4 neutropenia occurred in the first 2 patients. BV was continued until disease progression or toxicity. Planned accrual is 42 patients. Primary endpoint is progression-free survival. Secondary endpoints are response rate (RR), toxicity, time to progression and overall survival. Results: 20 pts have been accrued. Median age 57.5 yrs, males-55%, stage IV 90%, adenocarcinoma 75%. 18 pts are response evaluable (2 were too early to assess). 11/18 (61%) pts had a response (1 CR, 7 PR, 3 unconfirmed PR) (90% CI for RR is 0.42 - 0.77), and 3 had SD ( 17%) for a disease control rate of 78%. Currently the median treatment cycles for all pts are 6 (range 1–12). All pts are evaluable for toxicity. Grade 3- 4 toxicities: neutropenia 4, anemia 1, thrombocytopenia 2, lymphopenia 1, febrile neutropenia 1, fatigue 4, hypertension 1, GI 2, ALT/AST 3, pneumonitis 1, muscular weakness 1, metabolic 2, otitis media 1. Conclusions: The combination of P, G, and BV is a very active and tolerable treatment for NSCLC despite the preliminary nature of these results. Updated information will be presented at the meeting. This research is supported by Lilly Oncology and Genentech. [Table: see text]
Phase II study of sequentially administered mitomycin (MMC) and irinotecan (CPT-11) in patients (pts) with metastatic breast cancer (MBC)
Authors: E. Mrozek, J. Kolesar, J. Allen, D. Young, D. Angus, K. Kendra, C. A. Rhoades, M. A. Villalona-Calero, C. L. Shapiro
Journal: Journal of Clinical Oncology (2006)

10542 Background: MMC and CPT-11 are synergistic in preclinical studies, as MMC increases expression of Topoisomerase I (Topo I), the target of CPT-11. Three out of 5 heavily pretreated MBC pts benefited from MMC and CPT-11 in a phase I trial. We designed a phase II trial of this combination in MBC pts and hypothesized that increased Topo I expression in peripheral blood mononuclear cells (PBMC) would correlate with longer time to progression (TTP). Methods: Pt eligibility: ECOG PS 2 or less; no more than 2 prior chemotherapy regimens for MBC; adequate organ function; measurable and non-measurable disease were permitted. Treatment: intravenous (IV) MMC-6 mg/m 2 on day 1 and IV CPT-11–125 mg/m 2 on days 2 and 8 every 28 days. Genotyping of NQ01 (enzyme that activates MMC) was evaluated by pyrosequencing; Topo I gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) was evaluated in PBMC pretreatment, 24 hrs, 48 hrs, and 8 days after MMC. Results: Thirty-two pts enrolled with the following characteristics: median age 50 years (range 29–73); median PS 0 (range 0–2); postmenopausal 29 (91%) pts; estrogen receptor (ER) negative 14 (44%) pts; HER-2/neu 3+ by IHC 7 (22%) pts, and 10 (31%) pts were ER(−), PR(−) and HER-2/neu (−). Six (19%) pts had no prior chemotherapy; 7 (22%)-1 prior regimen; and 19 (59%)-2 prior regimens. Pts received a median of 4 cycles (range 1–12). Four (12%) pts experienced grade 4 toxicity (1-neutropenia without fever, 1-abdominal pain, 1-pulmonary embolism, and 1-diarrhea). The most common grade 3 toxicities were neutropenia in 13(41%) pts, nausea in 7 (22%) pts, diarrhea in 6 (19%) pts, fatigue in 5 (16%) pts, and thrombocytopenia in 2 (6%) pts. Median TTP was 4.7 months (95% CI, 4.0 to 5.4 months). For 10 triple negative pts the median TTP of 5.4 months was not different. Baseline and induced Topo I gene expression was greatest in NQ01 wild-type genotype, however, increased Topo I expression in PBMC was associated with shorter TTP. Conclusions: Sequential administration of MMC and CPT-11 had acceptable toxicities and antitumor activity. Our hypothesis that increased Topo I expression in PBMC correlates with longer TTP was incorrect. No significant financial relationships to disclose.
Neoadjuvant bevacizumab with weekly nanoparticle albumin bound nab-paclitaxel plus carboplatin followed by doxorubicin plus cyclophosphamide (AC) for triple-negative breast cancer.
Authors: J. C. Sachdev, L. E. Kronish, S. West, L. Schwartzberg, M. Jahanzeb
Journal: Journal of Clinical Oncology (2010)

TPS100 Background: Triple-negative breast cancers (TNBC) cluster with “basal like” subtype on genomic profiling. Overexpression of Secreted Protein Acidic and Rich in Cysteine (SPARC) has been observed in basal like breast cancer (Charaffe-Jaufrett et al. Oncogene 2006; 2273-84). Endothelial transcytosis of nab-paclitaxel occurs via albumin- gp60-caveolin 1 interaction. SPARC entraps the albumin resulting in higher intratumoral accumulation and increased efficacy of nab-paclitaxel (Desai et al. Translational Oncology 2009; 59-63). Exploiting this mechanism and the dysfunctional BRCA mediated DNA repair in basal like tumors, we hypothesize that nab-paclitaxel plus the DNA damaging drug carboplatin would demonstrate high response rates in TNBC. Bevacizumab may further enhance efficacy by blocking angiogenesis. Patients with TNBC who achieve a pathologic complete remission (pCR) to neoadjuvant treatment have a better disease-free survival (DFS) than those with less than a pCR. We hypothesize that high pCR rates can be achieved for patients with TNBC with this combination translating to an improved DFS than seen historically. Methods: Patients with palpable and operable TNBC ≥ 2 cm are eligible for this single stage phase II trial. The primary endpoint is pCR, defined as the absence of invasive tumor cells in the breast specimen. The planned sample size is 60, assuming a null hypothesis pCR rate of 25% vs. 40% for the alternate hypothesis. 10 patients have been accrued to date. Patients receive carboplatin AUC 6 day 1 and nab-paclitaxel 100 mg/m2 days 1, 8 and 15 of a 28-day cycle for 4 cycles followed by dose dense AC for 4 cycles. Bevacizumab is given at 10 mg/kg Q 2 weeks with chemotherapy for the first 6 cycles. Definitive surgical resection and radiation therapy are per institutional standards. Bevacizumab is continued postoperatively to complete 1 year of treatment. A core biopsy for collection of fresh tumor tissue is required prior to the start of study treatment. Blood is collected at baseline, and after 4 and 8 cycles for biomarker analysis. Gene expression profiling on fresh tissue will be undertaken for correlation with response. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, sanofi-aventis Abraxis BioScience, Genentech Abraxis BioScience, Genentech
A Dose-Response Study of Resistance of Leukemia L1210 to Cyclophosphamide2
Authors: William D. DeWys
Journal: JNCI Journal of the National Cancer Institute (1973)

A series of cyclophosphamide-resistant leukemia sublines were selected by serial drug treatment. Dose-response curves in vivo were determined by following cell outgrowth in drug-treated mice. Dose-response curves of sensitive and resistant lines were similar in form, with a shoulder region indicating accumulation of sublethal damage and an upward concavity of the exponential portion of the curve indicating inhomogeneity of sensitivity in the cell populations. Two-dose fractionation studies were interpreted as evidence that drug-resistant cells could repair sublethal damage, but neither the magnitude of this repair nor the rate of repair differed between sensitive and resistant cells. The dose-response curves differed in slope suggesting either a difference in cell uptake or a difference in intracellular handling of drug as mechanisms of resistance. These studies showed the usefulness of detailed analysis of dose-response curves and suggested the value of correlating dose-response curves with bio-chemical investigations of drug resistance.
Ramdomized 3-armed phase III study of S-1 monotherapy versus S-1/CDDP (SP) versus 5-FU/CDDP (FP) in patients (pts) with advanced gastric cancer (AGC): SC-101 study
Authors: M. Jin, H. Lu, J. Li, L. Shen, Z. Chen, Y. Shi, S. Song, S. Qin, J. Liu, X. Ouyang
Journal: Journal of Clinical Oncology (2008)

4533 Background: SP has been widely used against AGC in Japan. To further evaluate the efficacy and safety for SP in Chinese, we conducted a 3-arm study to investigate superiority of SP to S-1 and FP in pts with AGC. The primary endpoint was response rate (RR) and secondary endpoints were time to treatment failure (TTF), overall survival (OS) and safety. Methods: Treatments with Arm A (S-1 montherapy: S-1 80 mg/m2/d, d1∼28, q6w); Arm B (SP: S-1 80 mg/m2/d, d1∼21, plus CDDP 60 mg/m2 iv d8, q5w); Arm C (FP: 5-FU 600 mg/m2/d, civ, plus CDDP 20 mg/m2/d, iv 30 minutes, d1∼d5, q4w) were continued until disease progression or unacceptable toxicities. Eligibility criteria included unresectable/recurrent AGC, age≥18 years, and no prior chemotherapy. With 60 pts per arm, the trial was designed to have 80% power to detect an improvement of Arm B in RR (2 sided significance level p=0.025). CMH test was applied to RR. Log-rank test and Kaplan-Meier estimation were applied to TTF and OS. Used IRC (Independent Review Committee) evaluation as RR results. Arm C patients could switch to S-1 after treatment failure. Results: From July 2005 to Oct 2006, 230 pts (Arm A/B/C, 80/76/74) were randomized. The FAS were 224 patients (Arm A/B/C, 77/74/73). Median age was 57/56.5/58 yrs. RR(%) of Arm A/B/C were 24.7/37.8/19.2. The RR of Arm B was superior to Arm C (CMH p=0.021, odd ratio: 0.387, 95%CI:0.177∼0.847). The MST (days) were 267 (95%CI:202–323)/433 (95%CI:365-)/309 (95%CI:238-) at the time of analysis (Jan 15, 2007) when 42% of pts were dead. The OS of Arm B was superior to Arm C (Log-rank p=0.038) and Arm A (Log-rank p<0.001). The TTF (days) were 126 (95%CI: 92–152)/159 (95%CI:146–220)/85 (95%CI:66–106). The TTF of Arm B was superior to Arm C (Log-rank p<0.001) and Arm A (Log-rank p=0.008). 41 pts in Arm C switched to S-1 with the RR 14.6%. The most common grade 3/4 toxicities in Arm A/B/C (%) were: anemia, 2.5/5.3/5.4; leucopenia, 1.3/13.2/9.5; neutropenia, 3.8/17.1/16.2; PLT decreased, 0/6.6/12.2; nausea, 0/2.6/5.4; vomiting, 1.3/6.6/12.2; diarrhea, 3.8/6.6/0. No new drug- related SAE was observed. Conclusions: Both S-1 and SP regimen were found to be effective and well tolerated. Furthermore SP could be one of the standard regimens in Chinese pts with AGC. No significant financial relationships to disclose.
Malignant Tumors in American Black and Nigerian Children: A Comparative Study&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: E G Olisa, R Chandra, M A Jackson, J Kennedy, A O Williams
Journal: JNCI Journal of the National Cancer Institute (1975)

Results of a study on the relative frequencies of tumors in American black and Nigerian children were compared with data from the Childhood Cancer Registries in Manchester, United Kingdom, and Kampala, Uganda. The American black child living in Washington, D.C. and the Caucasian child living in Manchester had similar high frequencies for leukemia and glioma, whereas the incidence of lymphoma and retinoblastoma was low. African children living in Nigeria or Uganda had the opposite frequency patterns. These differences in frequencies of tumors between two ethnologically related population groups, American black and Nigerian, suggested the influence of environmental factors in the etiology of these tumors, even though exposure to environmental carcinogens was short. The rarity of Ewing's sarcoma and testicular tumors in American black and Nigerian children suggested a genetic influence.
A novel metronomic schedule of oral vinorelbine for the treatment of metastatic breast cancer in elderly patients: A phase II trial
Authors: R. Addeo, V. Faiola, G. Cennamo, R. Guarrasi, L. Montella, P. Iodice, A. Sgambato, E. Capasso, M. Caraglia, S. Del Prete
Journal: Journal of Clinical Oncology (2009)

1085 Background: Oral vinorelbine (VNR) is particularly useful in elderly patients due to its favorable toxicity profile. Several studies demonstrated that this drug seems to represent an active treatment for metastatic breast cancer (MCB). We evaluated the clinical efficacy and tolerance of metronomic chemotherapy with oral VNR. Methods: Women were eligible if they had a histologically proven untreated MBC and were &gt; 70 years old. A two-staged Simon accrual design was adopted for this phase II trial. Patients were required to have negative estrogen receptor status, at least one bidimensionally measurable target lesion, Karnofsky performance status &gt;70; life expectancy &gt; 3 months. Each patient received oral vinorelbine 80 mg/m 2 fractionated in days 1, 3, and 5, three week on-one week off, every 4 weeks, for a maximum of six cycles unless disease progression or unacceptable toxicity. Results: Thirty-two patients with MBC were eligible, assessable for response, and toxicity. The median age was 75 years (range 70–84), sixteen patients (50%) had a Karnofsky performance status of 90–100. The main comorbidities recorded were: hypertension in 9 (28%) patients and diabetes mellitus in 6 (19%). The overall response rate (on an intent-to-treat basis) was 41% (13 of 32; 95% CI, 20%-54%). Two complete response and 11 partial responses were noted. In addition, other 10 patients (31%) had stable disease of &gt; 4 months duration, and 9 patients (28 %) had disease progression. Median time to disease progression was 7.1 months and median overall survival was 12.7 months. The schedule was well tolerated, grade 3 toxicity was observed only in two patients. Conclusions: Metronomic oral VNR can be safely administered to elderly patients with MBC and is active in this population. Final data analysis will be presented. No significant financial relationships to disclose.
Patients With End Stage Congestive Heart Failure Have Decreased High Molecular Weight Von Willebrand Factor Multimers and Higher Plasma Levels Of Total TGF-β1: Implantation Of a Left Ventricular Assist Devices (LVAD) Exacerbates Both Abnormalities
Authors: Jasimuddin Ahamed, Juan Monteagudo, Mona Kinkhabwala, Mayte Suarez-Farinas, Arthur Reshad Garan, Barry S. Coller, Donna Mancini
Journal: Blood (2013)
Ultrastructure of Human Mesotheliomas 2
Authors: J. M. G. Davis
Journal: JNCI Journal of the National Cancer Institute (1974)

An electron microscope study of 5 human biopsy specimens from suspected mesotheliomas showed that the tumor cell fine structure was usually similar to that of mesotheliomas produced in laboratory animals by the intraperitoneal injection of asbestos dust. In most instances, the tumor cells had a well-developed granular endoplasmic reticulum, and the cell cytoplasm often contained bundles of microfilaments. In some, these microfilaments made up a large part of the cell volume. Glycogen was found in all the neoplasms examined, and some had large amounts. Lipid granules, seen in the cytoplasm of many tumor cells, had a characteristic crenated surface. The cell surface membranes were characteristically modified to form numerous surface processes of variable type found usually around most of the cell circumference. The processes ranged from irregularly shaped mi crovilli to globular projections like miniature pseudopodia, and often these 2 forms were intermingled on the same cell. One biopsy specimen that did not conform to this general pattern was proved at autopsy to be a bronchial carcinoma with secondary spread into the pleural cavity. This indicated that electron microscope examination may be extremely useful as an aid to diagnosis when only small biopsy specimens are available.
Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study.
Authors: M A Weiner, B Leventhal, M L Brecher, R B Marcus, A Cantor, P W Gieser, J L Ternberg, F G Behm, M D Wharam, A R Chauvenet
Journal: Journal of Clinical Oncology (1997)

To determine whether the addition of low-dose total-nodal irradiation (TNI) in pediatric patients with advanced-stage Hodgkin's disease who have received eight cycles of alternating mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) will improve the event-free survival (EFS) and overall survival (OS) when compared with patients who have received chemotherapy only.At diagnosis, 183 children and adolescents with stages IIB, IIIA2, IIIB, and IV Hodgkin's disease were randomized to receive eight cycles of alternating MOPP-ABVD with or without low-dose TNI.Of 183 patients, four were rendered ineligible before treatment was initiated. One hundred sixty-one of 179 patients (90%) were in complete remission (CR) at the completion of eight cycles of alternating MOPP-ABVD; 81 were in the chemotherapy-only group and proceeded to observation off therapy, whereas 80 of 161 were to receive combined modality therapy (CMT). Nine of 80 patients randomized at the time of diagnosis to receive CMT did not receive radiation (RT) because of a protocol violation, but were monitored for EFS and OS and included in all analyses. The estimated EFS and OS rates at 5 years for the 179 eligible patients are 79% and 92%, respectively. The actuarial EFS at 5 years was 80% for patients who received CMT and 79% for patients who received MOPP-ABVD only. The OS for the former group is estimated to be 87% and for the latter patients 96%. Age < or = 13 years of age at diagnosis and the attainment of a clinical CR after three cycles of chemotherapy were associated with a statistically significant improved EFS.Our results indicate that after the delivery of eight cycles of MOPP-ABVD, the addition of low-dose RT does not improve the estimated EFS or OS in pediatric patients with advanced-stage Hodgkin's disease.