Journal Title
Title of Journal: Invest New Drugs
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Abbravation: Investigational New Drugs
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Authors: Shaji K Kumar James Jett Randolph Marks Ronald Richardson Fernando Quevedo Timothy Moynihan Gary Croghan Svetomir N Markovic Keith C Bible Rui Qin Angelina Tan Julian Molina Scott H Kaufmann Charles Erlichman Alex A Adjei
Publish Date: 2013/10/01
Volume: 31, Issue: 5, Pages: 1201-1206
Abstract
Background Sorafenib a VEGFR and multitargeted kinase inhibitor and Bortezomib a proteasome inhibitor have clinical antineoplastic activities as single agents and combine synergistically in preclinical models Methods This Phase I study was undertaken to define the toxicity and the maximum tolerated doses MTD of the combination in patients with advanced solid tumors Patients with cytologic or histologic proof of unresectable solid tumors were treated with escalating doses of sorafenib twice daily and bortezomib days 1 4 8 and 11 intravenously with 21day cycles Results Fourteen patients 7 males median age 65 range 24–74 with renal 3 lung 3 pancreas 2 and breast adrenal gland melanoma spindle cell tumor chronic lymphocytic leukemia and multiple myeloma 1 each were enrolled All patients are off treatment 10 due to disease progression DLT was seen in two patients one grade 3 abdominal pain and grade 4 lipase elevation one with grade 3 vomiting at sorafenib 200 mg twice daily and bortezomib 13 mg/m2 establishing the MTD No grade 4 hematologic or grade 5 toxicities were seen One patient with renal cell cancer had a partial response and 5 patients attained stable disease Conclusions The combination of sorafenib and bortezomib was tolerated well The recommended phase 2 doses are sorafenib 200 mg twice daily continuously with bortezomib 1 mg/m2 on days 1 4 8 11 21 day cycles The combination shows preliminary signs of efficacy supporting phase 2 studiesWe are indebted to patients participating in this trial and to the enrolling investigators for their interest in and dedication to this study We also thank the clinical research associates and research protocol specialists at the Mayo Clinic Cancer Center for commitment to the completion of this trial and for administrative assistance
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- Cell death induction in resting lymphocytes by pan-Cdk inhibitor, but not by Cdk4/6 selective inhibitor
- A phase II study of isoflavones, erlotinib, and gemcitabine in advanced pancreatic cancer
- Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor
- Differences in maximum tolerated doses and approval doses of molecularly targeted oncology drug between Japan and Western countries
- Publication biases and phase II trials investigating anticancer targeted therapies
- Multi-drug inhibition of the HER pathway in metastatic colorectal cancer: Results of a phase I study of pertuzumab plus cetuximab in cetuximab-refractory patients
- LQB-118, a pterocarpanquinone structurally related to lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone]: a novel class of agent with high apoptotic effect in chronic myeloid leukemia cells
- Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer
- Deactylase inhibition in myeloproliferative neoplasms
- Synergistic activity of the Hsp90 inhibitor ganetespib with taxanes in non-small cell lung cancer models
- In vitro and in vivo antineoplastic and immunological effects of pterocarpanquinone LQB-118
- A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck
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- A phase I study of S-1 with concurrent radiotherapy in elderly patients with locally advanced non-small cell lung cancer
- (+)-Episesamin exerts anti-neoplastic effects in human hepatocellular carcinoma cell lines via suppression of nuclear factor-kappa B and inhibition of MMP-9
- Comprehensive analysis of clinical development and regulatory submission promotion schemes for oncologic drugs as the Japanese national projects
- First-in-human phase 1 study of filanesib (ARRY-520), a kinesin spindle protein inhibitor, in patients with advanced solid tumors
- Development and validation of a model that predicts early death among cancer patients participating in phase I clinical trials investigating cytotoxics
- A phase 1 study combining the HER3 antibody seribantumab (MM-121) and cetuximab with and without irinotecan
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- Histone deacetylase inhibitors enhance the anticancer activity of nutlin-3 and induce p53 hyperacetylation and downregulation of MDM2 and MDM4 gene expression
- A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma
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- Phase 2 study of CT-322, a targeted biologic inhibitor of VEGFR-2 based on a domain of human fibronectin, in recurrent glioblastoma
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- Phase II study of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer
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- A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143)
- Phase I study of the heat shock protein 90 (Hsp90) inhibitor onalespib (AT13387) administered on a daily for 2 consecutive days per week dosing schedule in patients with advanced solid tumors
- The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells
- Phase 1 trial of Anvirzel™ in patients with refractory solid tumors
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