ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Dose-Escalation Study of SCH 900776 in Combination With Cytarabine in Subjects With Acute Leukemias (Protocol No. P05247)
Personalized Cancer Therapy for Patients With Metastatic Medullary Thyroid or Metastatic Colon Cancer
Who cites it
68 citing papers in PubMed, 117 citations in OpenAlex.
- Randomized phase II trial of cytosine arabinoside with and without the CHK1 inhibitor MK-8776 in relapsed and refractory acute myeloid leukemia.Leukemia research · 2017Trial
- Discovery of BEND4 as a novel single-gene prognostic marker and therapeutic target for adverse AML.NPJ precision oncology · 2026Article
- CHK1 and CHK2 as Context-Dependent Rheostats of Genotoxic Stress: Implications for Cell Fate and Tumor Immunity.International journal of biological sciences · 2026Review
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- The Potential for Targeting GCancers · 2024Review
- Navigating the Maze of Kinases: CaMK-like Family Protein Kinases and Their Role in Atherosclerosis.International journal of molecular sciences · 2024Review
- Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.International journal of molecular sciences · 2024Review
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Article
- Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.Hematology reports · 2023Review
- HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation.The Journal of clinical investigation · 2023Article
- Claspin haploinsufficiency leads to defects in fertility, hyperplasia and an increased oncogenic potential.The Biochemical journal · 2022Article
- HMGA2 expression defines a subset of human AML with immature transcriptional signature and vulnerability to G2/M inhibition.Blood advances · 2022Article
- The identification of hub biomarkers and pathways in lung cancer and prognostic evaluation.Translational cancer research · 2022Article
- Chk1 Inhibition Potently Blocks STAT3 Tyrosine705 Phosphorylation, DNA-Binding Activity, and Activation of Downstream Targets in Human Multiple Myeloma Cells.Molecular cancer research : MCR · 2022Article
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Frontiers in oncology · 2022Review
- Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.Frontiers in oncology · 2022Review
- Review
- Comparative Activity and Off-Target Effects in Cells of the CHK1 Inhibitors MK-8776, SRA737, and LY2606368.ACS pharmacology & translational science · 2021Article
- Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
purposeIncorporation of cytarabine into DNA activates checkpoint kinase 1 (Chk1), which stabilizes stalled replication forks, induces S-phase slowing, and diminishes cytarabine cytotoxicity. The selective Chk1 inhibitor SCH 900776 abrogates cytarabine-induced S-phase arrest and enhances cytarabine cytotoxicity in acute leukemia cell lines and leukemic blasts in vitro. To extend these findings to the clinical setting, we have conducted a phase I study of cytarabine and SCH 900776. EXPERIMENTAL
designTwenty-four adults with relapsed and refractory acute leukemias received timed sequential, continuous infusion cytarabine 2 g/m(2) over 72 hours (667 mg/m(2)/24 hours) beginning on day 1 and again on day 10. SCH 900776 was administered as a 15- to 30-minute infusion on days 2, 3, 11, and 12. The starting dose of SCH 900776 was 10 mg/m(2)/dose.
resultsDose-limiting toxicities consisting of corrected QT interval prolongation and grade 3 palmar-plantar erythrodysesthesia occurred at 140 mg flat dosing (dose level 5, equivalent to 80 mg/m(2)). Complete remissions occurred in 8 of 24 (33%) patients, with 7 of 8 at 40 mg/m(2) or higher. SCH 900776 did not accumulate at any dose level. Marrow blasts obtained pretreatment and during therapy showed increased phosphorylation of H2Ax after SCH 900776 beginning at 40 mg/m(2), consistent with unrepaired DNA damage.
conclusionsThese data support a randomized phase II trial of cytarabine +/- SCH 900776 at a recommended flat dose of 100 mg (equivalent to 56 mg/m(2)) for adults with poor-risk leukemias. The trial (SP P05247) was registered at www.clinicaltrials.gov as NCT00907517.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.