Combination of analogs or derivatives of dianhydrogalactitol with platinum-containing antineoplastic agents to treat cancer

A kind of technology of two dehydrated dulcitol and antitumor agent, applied in substituted hexitol and fields, can solve problems such as effect limitation, unsatisfactory use and the like

Inactive Publication Date: 2018-05-11
DEL MAR PHARMA +3
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Even with commercial products, their end use is still limited by undesired effects

Method used

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  • Combination of analogs or derivatives of dianhydrogalactitol with platinum-containing antineoplastic agents to treat cancer
  • Combination of analogs or derivatives of dianhydrogalactitol with platinum-containing antineoplastic agents to treat cancer
  • Combination of analogs or derivatives of dianhydrogalactitol with platinum-containing antineoplastic agents to treat cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1101] In Vivo Efficacy of the Treatment of Non-Small Cell Lung Cancer Using Dideodulcitol in a Mouse Xenograft Model

[1102] background

[1103] The median overall survival time of patients with stage IV non-small cell lung cancer (NSCLC) is 4 months, and the 1-year and 5-year survival rates are less than 16% and 2%, respectively. NSCLC is usually treated with surgery followed by either tyrosine kinase inhibitor (TKI) (eg, erlotinib, gefitinib) treatment or platinum-based regimens (eg, cisplatin). TKIs have resulted in greatly improved outcomes for patients with EGFR mutations; however, TKI resistance has become a significant unmet medical need, and platinum-based therapies have a poor long-term prognosis. In addition, the incidence of brain metastases is higher in NSCLC patients and the prognosis is poorer.

[1104] Didodulcitol is a structurally unique bifunctional alkylating agent that targets the N of guanine 7 It mediates cross-linking between DNA strands, which is...

Embodiment 2

[1146] Use of dianhydrogalactitol as a novel treatment option for chemotherapy-resistant non-small cell lung cancer

[1147] WHO predicts that by 2025, the incidence of lung cancer may exceed 1 million cases per year, with non-small cell lung cancer (NSCLC) accounting for 90% of newly diagnosed cases. The median overall survival time of stage IV NSCLC patients is 4 months, and the 1-year and 5-year survival rates are less than 16% and 2%, respectively. Metastatic NSCLC is typically treated with either tyrosine kinase inhibitor (TKI) (eg, erlotinib, gefitinib) therapy or platinum-based regimens (eg, cisplatin). TKIs have resulted in greatly improved outcomes for patients with EGFR mutations; however, TKI resistance has become a significant unmet medical need, and platinum-based therapies have a poor long-term prognosis. In addition, the incidence of brain metastases is higher in NSCLC patients and the prognosis is poorer. Non-small cell lung cancer, in particular, accounts ...

Embodiment 3

[1188] Additional results on cell lines

[1189] background

[1190] The median overall survival time of patients with stage IV non-small cell lung cancer (NSCLC) is 4 months, and the 1-year and 5-year survival rates are less than 16% and 2%, respectively. NSCLC is typically treated with surgery followed by either tyrosine kinase inhibitor (TKI) therapy or platinum-based regimens (eg, cisplatin). TKIs have resulted in greatly improved outcomes for patients with EGFR mutations; however, TKI resistance has become a significant unmet medical need, and platinum-based therapies have a poor long-term prognosis. Didehydrodulcitol is a structurally unique bifunctional alkylating agent, and its N 7 It mediates cross-linking between DNA strands, which is different from the mechanism of action of TKI and cisplatin. Dideodulcitol has shown activity against non-small cell lung cancer in preclinical and clinical trials, suggesting that didhydrodulcitol may be a therapeutic option for...

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Abstract

The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is activeagainst tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together withother anti-neoplastic agents and can possess additive or super-additive effects.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of PCT Patent Application Serial No. PCT / The benefit of US2015 / 0244562, which claims the benefit of J.A. Bacha et al. on April 4, 2014, entitled "Treatment of Non-Small Cell Lung Cancer Using Didinodulcitol and Its Analogs and Derivatives" U.S. Provisional Patent Application Serial No. 61 / 975,587 and Claims to J. Batcha et al., filed October 10, 2014, entitled "Use of Didehydrodulcitol and Its Analogs and Derivatives in the Treatment of Non-Small Cell Lung Cancer ” of U.S. Consular Patent Application Serial No. 62 / 062,246. The contents of the above-mentioned PCT application and these two US provisional patents are incorporated herein by reference. technical field [0003] The present invention relates to the general field of proliferative diseases including oncology, the present invention focuses on novel methods and compositions for the improved utility of chemical agents, compound...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/336A61K33/24A61P35/00
Inventor 杰佛利·A·巴察丹尼斯·M·布朗安妮·斯提努
Owner DEL MAR PHARMA
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