ArticleCancer chemotherapy and pharmacology2014
Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors.
Article in Cancer chemotherapy and pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 195 citations in OpenAlex.
- A Phase 1/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer.British journal of cancer · 2023Trial
- A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients.BMC cancer · 2017Trial
- Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer.Investigational new drugs · 2016Trial
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Combination of CHK1 and CHK2 inhibitors exerts synergistic antitumor effects against neuroblastoma cells.Pediatric research · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Lysine demethylase 5D promotes CHEK1 inhibitor sensitivity through p38-mediated cyclooxygenase-2 expression in castration-resistant prostate cancer cells.The Journal of pharmacology and experimental therapeutics · 2025Article
- Comparative in vivo toxicology of ATR inhibitors ceralasertib, elimusertib, and berzosertib alone and in combination with ionizing radiation.Toxicology and applied pharmacology · 2025Article
- Therapeutic Targeting of DNA Damage Response Pathways inBrain tumor research and treatment · 2025Review
- Antitumor Activity of Radiation Therapy Combined with Checkpoint Kinase Inhibition in SHH/International journal of molecular sciences · 2025Article
- Guarding against digestive-system cancers: Unveiling the role of Chk2 as a potential therapeutic target.Genes & diseases · 2025Review
- Exploring drug repurposing as a therapeutic strategy for non-alcoholic fatty liver disease (NAFLD): identification of potential targets and pathways.Gastroenterology and hepatology from bed to bench · 2025Article
- Targeting synthetic lethality: an effective therapeutic approach in ovarian and endometrial cancers.Therapeutic advances in medical oncology · 2025Review
- The Potential for Targeting GCancers · 2024Review
- Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons.Cellular and molecular life sciences : CMLS · 2024Article
- Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons.Research square · 2024Article
- Construction of a Novel Mitochondria-Associated Gene Model for Assessing ESCC Immune Microenvironment and Predicting Survival.Journal of microbiology and biotechnology · 2024Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Checkpoint kinase 2 controls insulin secretion and glucose homeostasis.Nature chemical biology · 2024Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeAZD7762 is a Chk1 kinase inhibitor which increases sensitivity to DNA-damaging agents, including gemcitabine. We evaluated the safety of AZD7762 monotherapy and with gemcitabine in advanced solid tumor patients. EXPERIMENTAL
designIn this Phase I study, patients received intravenous AZD7762 on days 1 and 8 of a 14-day run-in cycle (cycle 0; AZD7762 monotherapy), followed by AZD7762 plus gemcitabine 750-1,000 mg/m(2) on days 1 and 8, every 21 days, in ascending AZD7762 doses (cycle 1; combination therapy).
resultsForty-two patients received AZD7762 6 mg (n = 9), 9 mg (n = 3), 14 mg (n = 6), 21 mg (n = 3), 30 mg (n = 7), 32 mg (n = 6), and 40 mg (n = 8), in combination with gemcitabine. Common adverse events (AEs) were fatigue [41 % (17/42) patients], neutropenia/leukopenia [36 % (15/42) patients], anemia/Hb decrease [29 % (12/42) patients] and nausea, pyrexia and alanine aminotransferase/aspartate aminotransferase increase [26 % (11/42) patients each]. Grade ≥3 AEs occurred in 19 and 52 % of patients in cycles 0 and 1, respectively. Cardiac dose-limiting toxicities occurred in two patients (both AZD7762 monotherapy): grade 3 troponin I increase (32 mg) and grade 3 myocardial ischemia with chest pain, electrocardiogram changes, decreased left ventricular ejection fraction, and increased troponin I (40 mg). AZD7762 exposure increased linearly. Gemcitabine did not affect AZD7762 pharmacokinetics. Two non-small-cell lung cancer patients achieved partial tumor responses (AZD7762 6 mg/gemcitabine 750 mg/m(2) and AZD7762 9 mg cohort).
conclusionsThe maximum-tolerated dose of AZD7762 in combination with gemcitabine 1,000 mg/m(2) was 30 mg. Although development of AZD7762 is not going forward owing to unpredictable cardiac toxicity, Chk1 remains an important therapeutic target.
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