ArticleInvestigational new drugs2011
Phase I study of 17-allylamino-17 demethoxygeldanamycin, gemcitabine and/or cisplatin in patients with refractory solid tumors.
Article in Investigational new drugs, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Phase II trial of gemcitabine and tanespimycin (17AAG) in metastatic pancreatic cancer: a Mayo Clinic Phase II Consortium study.Investigational new drugs · 2015Trial
- A phase II study of gemcitabine in combination with tanespimycin in advanced epithelial ovarian and primary peritoneal carcinoma.Gynecologic oncology · 2012Trial
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Identifying drug candidates for pancreatic ductal adenocarcinoma based on integrative multiomics analysis.Journal of gastrointestinal oncology · 2024Article
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- Novel peptide-based vaccine targeting heat shock protein 90 induces effective antitumor immunity in a HER2+ breast cancer murine model.Journal for immunotherapy of cancer · 2022Article
- Review
- The HSP90 inhibitor NVP-AUY922 inhibits growth of HER2 positive and trastuzumab-resistant breast cancer cells.Investigational new drugs · 2018Article
- Backbone and methyl resonance assignments of the 42 kDa human Hsc70 nucleotide binding domain in the ADP state.Biomolecular NMR assignments · 2017Article
- The remarkable multivalency of the Hsp70 chaperones.Cell stress & chaperones · 2017Review
- Calpain Genetic Disruption and HSP90 Inhibition Combine To Attenuate Mammary Tumorigenesis.Molecular and cellular biology · 2016Article
- Targeting Hsp90 in urothelial carcinoma.Oncotarget · 2015Review
- Topically applied Hsp90 inhibitor 17AAG inhibits UVR-induced cutaneous squamous cell carcinomas.The Journal of investigative dermatology · 2015Article
- Cytoplasmic HSP90α expression is associated with perineural invasion in pancreatic cancer.International journal of clinical and experimental pathology · 2014Article
- Phase I study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies.Investigational new drugs · 2013Article
- Molecular mechanism of 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced AXL receptor tyrosine kinase degradation.The Journal of biological chemistry · 2013Article
- Non-specific chemical inhibition of the Fanconi anemia pathway sensitizes cancer cells to cisplatin.Molecular cancer · 2012Article
- Hsp90 inhibitors and drug resistance in cancer: the potential benefits of combination therapies of Hsp90 inhibitors and other anti-cancer drugs.Biochemical pharmacology · 2012Review
- Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers.Biochimica et biophysica acta · 2012Review
- Targeting the dynamic HSP90 complex in cancer.Nature reviews. Cancer · 2010Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of 17-AAG, gemcitabine and/or cisplatin. Levels of the proteins Hsp90, Hsp70 and ILK were measured in peripheral blood mononuclear cell (PMBC) lysates to assess the effects of 17-AAG. EXPERIMENTAL
designPhase I dose-escalating trial using a "3 + 3" design performed in patients with advanced solid tumors. Once the MTD of gemcitabine + 17-AAG + cisplatin was determined, dose escalation of 17-AAG with constant doses of gemcitabine and cisplatin was attempted. After significant hematologic toxicity occurred, the protocol was amended to evaluate three cohorts: gemcitabine and 17-AAG; 17-AAG and cisplatin; and gemcitabine, 17-AAG and cisplatin with modified dosing.
resultsThe 39 patients enrolled were evaluable for toxicity and response. The MTD for cohort A was 154 mg/m(2) of 17-AAG, 750 mg/m(2) of gemcitabine, and 40 mg/m(2) of cisplatin. In cohort A, DLTs were observed at the higher dose level and included neutropenia, hyperbilirubinemia, dehydration, GGT elevation, hyponatremia, nausea, vomiting, and thrombocytopenia. The MTD for cohort C was 154 mg/m(2) of 17-AAG and 750 mg/m(2) of gemcitabine, with one DLT observed (alkaline phosphatase elevation) observed. In cohort C, DLTs of thrombocytopenia, fever and dyspnea were seen at the higher dose level. The remaining cohorts were closed to accrual due to toxicity. Six patients experienced partial responses. Mean Hsp90 levels were decreased and levels of Hsp70 were increased compared to baseline.
conclusions17-AAG in combination with gemcitabine and cisplatin demonstrated antitumor activity, but significant hematologic toxicities were encountered. 17-AAG combined with gemcitabine is tolerable and has demonstrated evidence of activity at the MTD. The recommended phase II dose is defined as 154 mg/m(2) of 17-AAG and 750 mg/m(2) of gemcitabine, and is currently being investigated in phase II studies in ovarian and pancreatic cancers. There is no recommended phase II dose for the cisplatin-containing combinations.
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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.