ArticleInvestigational new drugs2018
A phase I and pharmacokinetic study of taladegib, a Smoothened inhibitor, in Japanese patients with advanced solid tumors.
Article in Investigational new drugs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed.
- Evaluation of the Tolerability of Hedgehog Pathway Inhibitors in the Treatment of Advanced Basal Cell Carcinoma: A Narrative Review of Treatment Strategies.American journal of clinical dermatology · 2024Review
- Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities.International journal of molecular sciences · 2024Review
- Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer.International journal of molecular sciences · 2024Review
- Current Status of Hedgehog Signaling Inhibitors.Current topics in medicinal chemistry · 2024Review
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- New Emerging Treatment Options for Advanced Basal Cell Carcinoma and Squamous Cell Carcinoma.Advances in therapy · 2022Review
- Breast cancer: molecular mechanisms of underlying resistance and therapeutic approaches.American journal of cancer research · 2022Review
- The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis.Biomedicines · 2021Review
- Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.Signal transduction and targeted therapy · 2021Review
- Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents.Signal transduction and targeted therapy · 2021Review
- Cancer stem cells: a major culprit of intra-tumor heterogeneity.American journal of cancer research · 2021Review
- Emerging role of tumor cell plasticity in modifying therapeutic response.Signal transduction and targeted therapy · 2020Review
- Hedgehog Pathway Inhibitors: A New Therapeutic Class for the Treatment of Acute Myeloid Leukemia.Blood cancer discovery · 2020Review
- Review
- Hedgehog Pathway Inhibition for the Treatment of Basal Cell Carcinoma.Targeted oncology · 2019Review
- Safety and Tolerability of Sonic Hedgehog Pathway Inhibitors in Cancer.Drug safety · 2019Review
- Current Advance of Therapeutic Agents in Clinical Trials Potentially Targeting Tumor Plasticity.Frontiers in oncology · 2019Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background This phase I dose-escalation study investigated the safety of the Smoothened inhibitor taladegib in Japanese patients with advanced solid tumors. Methods Patients received taladegib orally once daily for 28-day cycles, using a 3 + 3 dose-escalation method. The primary objective was the safety and tolerability of taladegib at doses up to the global recommended dose (400 mg). Secondary objectives included pharmacokinetics, changes in skin glioma-associated oncogene homolog 1 (Gli1) transcript levels, and antitumor activity. Results Nineteen patients received treatment (100 mg: 3; 200 mg: 3; 400 mg: 13). No dose-limiting toxicities (DLTs) were observed at doses of 100 mg or 200 mg; 3 of the 9 patients evaluable for DLTs at the 400 mg dose level experienced DLTs (thrombocytopenia: 1; decreased appetite: 2). The most commonly reported treatment-related adverse events were dysgeusia (13/19, 68.4%), decreased appetite (12/19, 63.2%), nausea (9/19, 47.4%), fatigue (9/19, 47.4%), and vomiting (6/19, 31.6%). The pharmacokinetic profile suggested that exposure to taladegib was higher in Japanese than non-Japanese patients, possibly related to differences in body weight and/or drug formulation. At all dose levels, a high level of inhibition of skin Gli1 transcript levels was observed after 15 and 30 days of exposure to taladegib. Partial response was achieved by 1 patient (basal cell carcinoma of the skin) and stable disease by 4 patients. Conclusions Taladegib doses of 100 mg and 200 mg, but not the global recommended dose of 400 mg, were well tolerated in this population of Japanese patients with advanced solid tumors.
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