ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- CT-guided intratumoral immunotherapy for advanced solid tumors: a prospective clinical study of safety and systemic antitumor effects.Frontiers in immunology · 2026Trial
- Exploring the landscape of targetable alterations in patients with glioblastoma.Nature reviews. Clinical oncology · 2026Review
- RAS signaling at the crossroads of radioresistance and tumor immunity.Journal for immunotherapy of cancer · 2026Review
- Evaluating "brain permeability": A critical issue for the development of therapeutic agents for primary and metastatic brain tumors.Neuro-oncology · 2026Review
- Glioblastoma Multiforme: Current Developments in Molecular Pathways, Magnetic Field-Based Interventions, and Personalized Therapy.Journal of clinical practice and research · 2026Review
- Article
- The evolution of chemotherapy in brain tumors: from historical milestones to precision medicine in glioblastoma.Exploration of targeted anti-tumor therapy · 2026Review
- A postoperative in situ drug delivery system based on biphasic drug-release and "Three-in-One" Effect of curcumin to inhibit the recurrence of glioma.International journal of pharmaceutics: X · 2025Article
- Glioma drug development benefits from emerging phase 0 and window-of-opportunity trial paradigm.Cell communication and signaling : CCS · 2025Review
- Targeting replication stress in glioblastoma: From genotoxic treatment and inhibitors of the DNA damage response to immunotherapy.Neuro-oncology advancesReview
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23 authors.
Funding
Abstract
purposeAdavosertib is an oral small-molecule inhibitor of Wee1. The Adult Brain Tumor Consortium conducted a phase I study evaluating adavosertib in combination with radiation (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM), as well as a surgical window-of-opportunity study in recurrent GBM. PATIENTS AND
methodsThe MTD of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in two separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ. A combination cohort with both concurrent and adjuvant adavosertib at MTD followed. We also performed intratumoral drug distribution studies in patients with recurrent GBM undergoing surgery.
resultsAs separate cohorts, the MTD for concurrent adavosertib with RT/TMZ was 200 mg daily Monday through Friday × 6 weeks during RT, and the MTD for adjuvant adavosertib with TMZ was 425 mg daily for 5 days of each 28-day cycle. However, six of 12 patients experienced dose-limiting toxicities (DLT) in the combination cohort. The mean ratios of the intratumoral to plasma concentration of adavosertib were 4.18 ± 3.36 for contrast-enhancing tissue and 0.74 ± 0.63 in nonenhancing tissue.
conclusionsAdavosertib at 200 mg daily Monday through Friday × 6 weeks with RT/TMZ and at 425 mg daily on a 5-day/28-day cycle with TMZ had an unacceptable DLT rate. Additional dose levels in combination cohorts resulted in DLT, and we deemed concurrent adavosertib too toxic for further examination. Adavosertib 425 mg daily on a 5-day/28-day cycle with adjuvant TMZ is the recommended phase II dosage. Tissue pharmacokinetics in tissue homogenates and by microdialysis provided complementary information about drug penetration.
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