SARC025 arms 1 and 2: A phase 1 study of the poly(ADP-ribose) polymerase inhibitor niraparib with temozolomide or irinotecan in patients with advanced Ewing sarcoma.

Abstract:

BACKGROUND:In preclinical Ewing sarcoma (ES) models, poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors were identified as a potential therapeutic strategy with synergy in combination with cytotoxic agents. This study evaluated the safety and dosing of the PARP1/2 inhibitor niraparib (NIR) with temozolomide (TMZ; arm 1) or irinotecan (IRN; arm 2) in patients with pretreated ES. METHODS:Eligible patients in arm 1 received continuous NIR daily and escalating TMZ (days 2-6 [D2-6]) in cohort A. Subsequent patients received intermittent NIR dosing (cohort B), with TMZ re-escalation in cohort C. In arm 2, patients were assigned to NIR (days 1-7 [D1-7]) and escalating doses of IRN (D2-6). RESULTS:From July 2014 to May 2018, 29 eligible patients (23 males and 6 females) were enrolled in arms 1 and 2, which had 7 dose levels combined. Five patients experienced at least 1 dose-limiting toxicity (DLT) in arm 1 (grade 4 [G4] neutropenia for >7 days or G4 thrombocytopenia), and 3 patients experienced at least 1 DLT in arm 2 (grade 3 [G3] colitis, G3 anorexia, or G3 alanine aminotransferase elevation). The maximum tolerated dose was NIR at 200 mg every day on D1-7 plus TMZ at 30 mg/m2 every day on D2-6 (arm 1) or NIR at 100 mg every day on D1-7 plus IRN at 20 mg/m2 every day on D2-6 (arm 2). One confirmed partial response was observed in arm 2; the median progression-free survival was 9.0 weeks (95% CI, 7.0-10.1 weeks) and 16.3 weeks (95% CI, 5.1-69.7 weeks) in arms 1 and 2, respectively. The median decrease in tumor poly(ADP-ribose) activity was 89% (range, 83%-98%). CONCLUSIONS:The combination of NIR and TMZ or IRN was tolerable, but at lower doses in comparison with conventional cytotoxic combinations. A triple-combination study of NIR, IRN, and TMZ has commenced.

journal_name

Cancer

journal_title

Cancer

authors

Chugh R,Ballman KV,Helman LJ,Patel S,Whelan JS,Widemann B,Lu Y,Hawkins DS,Mascarenhas L,Glod JW,Ji J,Zhang Y,Reinke D,Strauss SJ

doi

10.1002/cncr.33349

subject

Has Abstract

pub_date

2020-12-08 00:00:00

eissn

0008-543X

issn

1097-0142

pub_type

杂志文章

相关文献

CANCER文献大全
  • A comparison of cancer risk in Crohn's disease and ulcerative colitis.

    abstract::The authors estimated cancer risk among 589 patients hospitalized with Crohn's disease between 1960-1976 by calculating the ratios of observed number of cancers (O) in our hospital sample to the expected number of cancers (E) based on the age- and sex-specific cancer rates of a standard population. The authors then co...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19811215)48:12<2742::aid-cncr282

    authors: Greenstein AJ,Sachar DB,Smith H,Janowitz HD,Aufses AH Jr

    更新日期:1981-12-15 00:00:00

  • Facilitating clinical trials. The expanding role of the nurse.

    abstract::Clinical trials are becoming increasingly difficult to carry out in the face of a changing health care delivery system. The reluctance of third party payers to reimburse for experimental therapy and the growing practice of providers to limit resources allocated for the care of cancer patients undergoing such therapies...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.2820671818

    authors: Engelking C

    更新日期:1991-03-15 00:00:00

  • Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

    abstract:BACKGROUND:Fludarabine plus busulfan (FB) and fludarabine plus melphalan (FM) are 2 widely used reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (allo-SCT). METHODS:The current survey compared transplantation outcomes for a cohort of 394 acute myeloid leukemia (AML) ...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.29163

    authors: Baron F,Labopin M,Peniket A,Jindra P,Afanasyev B,Sanz MA,Deconinck E,Nagler A,Mohty M

    更新日期:2015-04-01 00:00:00

  • Prognostic factors in telecobalt therapy for early supraglottic carcinoma.

    abstract:BACKGROUND:The local control rates of T1 and T2 supraglottic carcinoma treated with radiation alone were reported as 71% to 92% and 59% to 83%, respectively. The factors that affect the local control rate for early supraglottic carcinoma were investigated. METHODS:From 1967 through 1985, 100 cases with early supraglot...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19930701)72:1<57::aid-cncr282072

    authors: Inoue T,Matayoshi Y,Inoue T,Ikeda H,Teshima T,Murayama S

    更新日期:1993-07-01 00:00:00

  • A retrospective analysis of 10-year survivors from carcinoma of the lung.

    abstract::From 1949 to 1972, 4732 patients with carcinomas of the lung were seen. Of these, 118 patients were found alive at 10 years from their initial diagnosis and treatment. This number represents only 2.5% of all lung cancers seen because many have been lost to follow-up within the first ten years, and their true status is...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19840315)53:6<1405::aid-cncr2820

    authors: Temeck BK,Flehinger BJ,Martini N

    更新日期:1984-03-15 00:00:00

  • Microsatellite instability and expression of MLH1 and MSH2 in carcinomas of the small intestine.

    abstract:BACKGROUND:Carcinomas of the small intestine are rare, but the risk is greatly increased in patients with hereditary nonpolyposis colorectal cancer (HNPCC) due to an inherited mismatch repair (MMR) gene mutation, most commonly affecting the genes MLH1 or MSH2. Defective MMR is characterized by microsatellite instabilit...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.11197

    authors: Planck M,Ericson K,Piotrowska Z,Halvarsson B,Rambech E,Nilbert M

    更新日期:2003-03-15 00:00:00

  • EphA2 overexpression is associated with angiogenesis in ovarian cancer.

    abstract:BACKGROUND:EphA2 is overexpressed in the majority of ovarian cancers and predicts poor clinical outcome. Based on EphA2's emerging role in angiogenesis, we hypothesized that tumors overexpressing EphA2 demonstrate greater microvessel density (MVD) and matrix metalloproteinase (MMP) expression. METHODS:After Institutio...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.22415

    authors: Lin YG,Han LY,Kamat AA,Merritt WM,Landen CN,Deavers MT,Fletcher MS,Urbauer DL,Kinch MS,Sood AK

    更新日期:2007-01-15 00:00:00

  • Transplantation of human basal cell carcinomas to athymic mice.

    abstract::Basal cell carcinomas (BCCs) obtained from 22 subjects undergoing microscopically controlled surgery were transplanted to 40 athymic (nude) mice. With no further immunosuppression of the mice, no tumor growth was noted in the first 14 attempts. When mice were further immunosuppressed with anti-lymphocyte serum (ALS) i...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19850801)56:3<519::aid-cncr28205

    authors: Grimwood RE,Johnson CA,Ferris CF,Mercill DB,Mellette JR,Huff JC

    更新日期:1985-08-01 00:00:00

  • Heterotransplantation of small cell lung carcinoma into nude mice. Stability of the phenotypic characters.

    abstract::In order to validate xenografted small cell lung carcinomas (SCLC) for biological studies, the authors established 12 lung neuroendocrine (NE) tumors (eight typical SCLC and four atypical NE tumors [ANE]) by heterotransplantation onto nude mice. Their characterization was performed using serial ultrastructural, enzyma...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19890915)64:6<1238::aid-cncr2820

    authors: Brambilla E,Jacrot M,Batandier C,Brichon PY,Morel F,Nagy-Mignotte H,Paramelle B,Brambilla C

    更新日期:1989-09-15 00:00:00

  • Juvenile xanthogranuloma. Clinicopathologic analysis and immunohistochemical study of 57 patients.

    abstract::Fifty-seven cases of juvenile xanthogranuloma that fulfilled the classic description of histologic findings of the disease were analyzed clinicopathologically and immunohistochemically. Two forms could be distinguished: 47 cases of the infantile form and 10 of the adolescent and young adult form. The infantile lesion ...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19851101)56:9<2280::aid-cncr2820

    authors: Sonoda T,Hashimoto H,Enjoji M

    更新日期:1985-11-01 00:00:00

  • Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma.

    abstract:BACKGROUND:Vascular endothelial growth factor-C (VEGF-C) plays an important role in lymphangiogenesis and activates VEGF receptor-3 (VEGFR-3). Lymphatic spread is an important prognostic factor in patients with lung adenocarcinoma. The aim of the current study was to determine whether the expression of VEGF-C and VEGFR...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.21366

    authors: Kojima H,Shijubo N,Yamada G,Ichimiya S,Abe S,Satoh M,Sato N

    更新日期:2005-10-15 00:00:00

  • Prostate carcinoma presentation, diagnosis, and staging: an update form the National Cancer Data Base.

    abstract:BACKGROUND:Based on the 1998 Patient Care Evaluation (PCE) from the American College of Surgeons National Cancer Data Base (NCDB), the authors described contemporary nationwide patterns of prostate carcinoma presentation, diagnosis, and staging. METHODS:The authors reviewed 54,212 cases from the 1998 PCE. Demographics...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.11635

    authors: Miller DC,Hafez KS,Stewart A,Montie JE,Wei JT

    更新日期:2003-09-15 00:00:00

  • Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction.

    abstract::The authors retrospectively searched for human papillomavirus (HPV) types 16 and 18 in 60 cases of carcinoma arising from the nasal cavities (NC) and paranasal sinuses (PS) by using the polymerase chain reaction (PCR) on DNA extracted from formalin-fixed, paraffin-embedded tissues. In cases of SCC (n = 49), the author...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19920115)69:2<353::aid-cncr28206

    authors: Furuta Y,Takasu T,Asai T,Shinohara T,Sawa H,Nagashima K,Inuyama Y

    更新日期:1992-01-15 00:00:00

  • A comparative study of copper-67 radiolabeling and kinetic stabilities of antibody-macrocycle chelate conjugates.

    abstract:BACKGROUND:The development of new chelating agents and radiolabeling protocols is essential to progress in radioimmunotherapy with antibody-chelate conjugates. METHODS:Immunoconjugates of four polyazamacrocycles with N-bonded acetate groups were prepared by conjugation via 2-iminothiolane to Lym-1, a murine antilympho...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19940201)73:3+<779::aid-cncr2820

    authors: Kukis DL,Diril H,Greiner DP,DeNardo SJ,DeNardo GL,Salako QA,Meares CF

    更新日期:1994-02-01 00:00:00

  • Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single-center, open-label, phase 2 study.

    abstract:BACKGROUND:Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX. METHODS:In this phase 2, single-arm,...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.30445

    authors: Gulhati P,Raghav K,Shroff RT,Varadhachary GR,Kopetz S,Javle M,Qiao W,Wang H,Morris J,Wolff RA,Overman MJ

    更新日期:2017-05-15 00:00:00

  • The impact of age, treatment, and symptoms on the physical and mental health of cancer patients. A longitudinal perspective.

    abstract:BACKGROUND:To describe continuing care and rehabilitation needs of cancer patients, a longitudinal design (6 months) was performed among patients 50 years of age and older with solid tumors. The study examined how age, type of treatment, site of cancer, and symptom experience affect physical functioning and their menta...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19941001)74:7+<2128::aid-cncr282

    authors: Given CW,Given BA,Stommel M

    更新日期:1994-10-01 00:00:00

  • Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma: a Swiss experience with 588 tumors.

    abstract:BACKGROUND:A new, internationally accepted histologic classification of renal cell carcinoma (RCC) and a new edition of the TNM staging system were introduced in 1997. In the latter, there was a dramatic change in the pT classification of organ-confined renal cancer in which the break point between category pT1 and pT2...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:

    authors: Moch H,Gasser T,Amin MB,Torhorst J,Sauter G,Mihatsch MJ

    更新日期:2000-08-01 00:00:00

  • The use of a tumor colony assay in predicting chemotherapeutic drug response in murine bladder cancer.

    abstract::A tumor colony assay (TCA) was evaluated for its ability to predict anticancer drug responses in an N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT)-induced murine bladder tumor (MBT) model. Ten anticancer drugs were evaluated in vivo and in vitro using four MBT cell lines (40 drug responses). Using the optimum c...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19830815)52:4<619::aid-cncr28205

    authors: Niell HB,Soloway MS,Wood CA,McCallum LW,Webster K

    更新日期:1983-08-15 00:00:00

  • B-cell lymphoma in severe combined immunodeficiency not associated with the Epstein-Barr virus.

    abstract::Patients with congenital and acquired immunodeficiencies are at increased risk for the development of B-cell lymphoproliferative disorders. When the appropriate tests have been performed, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) or EBV DNA has been found in tissues from these tumors. These data have provide...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0142(19871215)60:12<2941::aid-cncr282

    authors: Garcia CR,Brown NA,Schreck R,Stiehm ER,Hudnall SD

    更新日期:1987-12-15 00:00:00

  • C-cell disease of the thyroid gland in multiple endocrine neoplasia, type 2b.

    abstract::Multiple endocrine neoplasia, type 2b (MEN 2b) is a disorder characterized by C-cell disease of the thyroid gland (medullary carcinoma or C-cell hyperplasia, or both), pheochromocytoma, ganglioneuromatosis, and skeletal and connective tissue abnormalities. The medullary thyroid carcinoma (MTC) is bilateral and multice...

    journal_title:Cancer

    pub_type: 杂志文章,评审

    doi:10.1002/1097-0142(197912)44:6<2173::aid-cncr282044

    authors: Carney JA,Sizemore GW,Hayles AV

    更新日期:1979-12-01 00:00:00

  • Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis.

    abstract:BACKGROUND:It has been suggested that tissue factor (TF) plays an important role in tumor metastasis. Its expression in sarcoma cells was reported to up-regulate the vascular endothelial growth factor (VEGF) gene and thereby enhance tumor angiogenesis, which is essential to tumor metastasis. Although many malignant tum...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0142(20000115)88:2<295::aid-cnc

    authors: Seto S,Onodera H,Kaido T,Yoshikawa A,Ishigami S,Arii S,Imamura M

    更新日期:2000-01-15 00:00:00

  • Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database.

    abstract:BACKGROUND:The incidence of rectal cancer in the United States in young patients is considered to be low. Underestimating this incidence may result in a failure to diagnose younger patients with rectal cancer in a timely manner. METHODS:The authors conducted a retrospective cohort study using Surveillance, Epidemiolog...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.25432

    authors: Meyer JE,Narang T,Schnoll-Sussman FH,Pochapin MB,Christos PJ,Sherr DL

    更新日期:2010-09-15 00:00:00

  • Onycholysis as a complication of systemic chemotherapy: report of five cases associated with prolonged weekly paclitaxel therapy and review of the literature.

    abstract:BACKGROUND:Onycholysis has been reported in association with the use of several noncytotoxic drugs and with chemotherapy in 135 patients. Onycholysis may be precipitated by exposure to ultraviolet radiation. METHODS:The authors studied 91 patients who received paclitaxel and 187 patients who received doxorubicin. RES...

    journal_title:Cancer

    pub_type: 杂志文章,评审

    doi:10.1002/(sici)1097-0142(20000515)88:10<2367::aid-c

    authors: Hussain S,Anderson DN,Salvatti ME,Adamson B,McManus M,Braverman AS

    更新日期:2000-05-15 00:00:00

  • Early surveillance is associated with less incidence and severity of breast cancer-related lymphedema compared with a traditional referral model of care.

    abstract:BACKGROUND:Bioimpedance spectroscopy (BIS) has enabled the early identification of breast cancer-related lymphedema. In this study, differences in health service metrics and in the incidence of breast cancer-related lymphedema are evaluated in an early surveillance model of care compared with a traditional referral mod...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.31873

    authors: Koelmeyer LA,Borotkanics RJ,Alcorso J,Prah P,Winch CJ,Nakhel K,Dean CM,Boyages J

    更新日期:2019-03-15 00:00:00

  • Determinants of the recommended phase 2 dose of molecular targeted agents.

    abstract:BACKGROUND:The recommended phase 2 dose (RP2D) of anticancer agents is determined traditionally by dose-limiting toxicities. Nontoxicity or biological endpoints such as pharmacokinetics, pharmacodynamics, and efficacy can also be used to identify RP2D, which may be relevant to molecularly targeted agents (MTAs). METHO...

    journal_title:Cancer

    pub_type: 杂志文章,meta分析

    doi:10.1002/cncr.30579

    authors: Hansen AR,Cook N,Amir E,Siu LL,Abdul Razak AR

    更新日期:2017-04-15 00:00:00

  • 11p15.5 epimutations in children with Wilms tumor and hepatoblastoma detected in peripheral blood.

    abstract:BACKGROUND:Constitutional or somatic mosaic epimutations are increasingly recognized as a mechanism of gene dysregulation resulting in cancer susceptibility. Beckwith-Wiedemann syndrome is the cancer predisposition syndrome most commonly associated with epimutation and is extremely variable in its phenotypic presentati...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.32907

    authors: Fiala EM,Ortiz MV,Kennedy JA,Glodzik D,Fleischut MH,Duffy KA,Hathaway ER,Heaton T,Gerstle JT,Steinherz P,Shukla N,McNeer N,Tkachuk K,Bouvier N,Cadoo K,Carlo MI,Latham A,Dubard Gault M,Joseph V,Kemel Y,Kentsis A,

    更新日期:2020-07-01 00:00:00

  • Oral bisphosphonates: A review of clinical use in patients with bone metastases.

    abstract:BACKGROUND:This study was conducted to review the efficacy and safety of oral bisphosphonates for the treatment of bone metastases in cancer patients. METHODS:Available published clinical studies of oral bisphosphonates in bone metastases from 1980 to the present were identified through a MEDLINE search and from liter...

    journal_title:Cancer

    pub_type: 杂志文章,评审

    doi:

    authors: Major PP,Lipton A,Berenson J,Hortobagyi G

    更新日期:2000-01-01 00:00:00

  • The yield of routine chest radiography in children with cancer hospitalized for fever and neutropenia.

    abstract::A routine admission chest radiograph (CXR) in pediatric patients with cancer who are admitted to the hospital for fever and neutropenia has been advised because the signs and symptoms of pneumonia may be absent. The authors studied 131 consecutive patient admissions for fever and neutropenia to evaluate the diagnostic...

    journal_title:Cancer

    pub_type: 临床试验,杂志文章

    doi:10.1002/1097-0142(19910901)68:5<940::aid-cncr28206

    authors: Katz JA,Bash R,Rollins N,Cash J,Buchanan GR

    更新日期:1991-09-01 00:00:00

  • The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS.

    abstract:BACKGROUND:The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene resulting from the chromosome inversion inv(2)(p21;p23) recently was identified in nonsmall cell lung cancer (NSCLC). The authors of this study investigated the frequency, genetic and clinicopathologic prof...

    journal_title:Cancer

    pub_type: 杂志文章

    doi:10.1002/cncr.24181

    authors: Wong DW,Leung EL,So KK,Tam IY,Sihoe AD,Cheng LC,Ho KK,Au JS,Chung LP,Pik Wong M,University of Hong Kong Lung Cancer Study Group.

    更新日期:2009-04-15 00:00:00

  • Prevention of radiation enteritis by an absorbable polyglycolic acid mesh sling. A 60-case multicentric study.

    abstract::Radiation-induced small bowel injury is a limiting factor to postoperative tumoricidal pelvic doses exceeding 4500 to 5000 cGy. Data from a review of the literature showed the inadequacy of medical measures and the bad reproducibility of radiation therapeutic attempts to decrease small intestine damage. Recent studies...

    journal_title:Cancer

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1002/1097-0142(19911215)68:12<2545::aid-cncr282

    authors: Rodier JF,Janser JC,Rodier D,Dauplat J,Kauffmann P,Le Bouedec G,Giraud B,Lorimier G

    更新日期:1991-12-15 00:00:00