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Quinoline compound for combined treatment of esophageal cancer

A technology for esophageal cancer and compounds, applied in the field of pharmaceutical preparations and medicine, can solve the problems of cell vacuolation, nausea, and lumen expansion

Pending Publication Date: 2020-12-25
CHIA TAI TIANQING PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The most commonly used DF regimen (DDP+5-FU) for esophageal cancer has greater gastrointestinal toxicity, prone to nausea, vomiting, stomatitis, gastrointestinal mucosal damage, etc.; DFT regimen (PTX+DDP+5-FU) is prone to Bone marrow suppression occurs, and at the same time, cisplatin causes damage to the proximal renal tubules, resulting in vacuolation of cells, dilation of the lumen, appearance of hyaline casts, increased blood urea nitrogen and creatinine, etc.

Method used

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  • Quinoline compound for combined treatment of esophageal cancer
  • Quinoline compound for combined treatment of esophageal cancer
  • Quinoline compound for combined treatment of esophageal cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0137] Esophageal squamous cell carcinoma confirmed by histology or cytology, and patients with locally advanced unresectable, local recurrence or distant metastasis; the commonly used method of block randomization is divided into group A and group B, respectively combined with drug therapy Rotinib and irinotecan, and irinotecan alone, the specific dosage regimen is as follows:

[0138] Group A (test group):

[0139] Anlotinib hydrochloride combined with irinotecan: Take anlotinib hydrochloride capsules 12mg (specification: 12mg / capsule) on an empty stomach every day, orally for 2 weeks and stop for 1 week, irinotecan 65mg / m 2 , d1, d8 intravenous infusion. 3 weeks as a treatment cycle, until disease progression (PD) or toxicity intolerable.

[0140] Group B (control group):

[0141] Irinotecan 65mg / m 2 , d1, d8 intravenous infusion. 3 weeks as a treatment cycle, until disease progression (PD) or toxicity intolerable.

[0142] The general description of the patients is s...

Embodiment 2

[0152] Patients with locoregional recurrence of esophageal squamous cell carcinoma confirmed by histopathology and / or cytology examination, radiotherapy combined with anlotinib, the specific administration is as follows:

[0153] Radiation therapy: 59.4Gy / 1.8Gy / 33Fx; anlotinib hydrochloride capsules: 12mg po d1-14 on day 1 to day 14 of each cycle, every 3 weeks as a treatment cycle.

[0154] The observed efficacy indicators include objective response rate (ORR), treatment-related toxicity, local control rate (LCR), distant metastasis rate (DMR), progression-free survival (PFS), and overall survival (OS).

[0155] This study shows that for patients with esophageal cancer, the treatment regimen of anlotinib combined with radiotherapy has clinical benefits.

Embodiment 3

[0157] Potentially resectable stage IIB-IVA esophageal squamous cell carcinoma confirmed by histopathology or cytology, with at least one measurable lesion after treatment (helical CT scan long diameter ≥ 10 mm, meeting the requirements of RESCIST version 1.1 criteria) The patient was given anlotinib, paclitaxel liposome and nedaplatin in combination for preoperative neoadjuvant therapy, and the specific dosage regimen was as follows:

[0158] Anlotinib Hydrochloride Capsules: Take it on an empty stomach before breakfast, once a day, 1 capsule (12mg) each time, take 2 weeks in a row, every 3 weeks as a cycle, preoperative administration for 2 cycles, postoperative administration for 4 -6 cycles, then anlotinib maintenance therapy until progression;

[0159] Paclitaxel liposome: 175mg / m 2 , intravenous infusion on the first day of each cycle, every 3 weeks as a cycle, 2 cycles of preoperative administration, and 4-6 cycles of postoperative administration;

[0160] Nedaplatin:...

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Abstract

The application belongs to the technical field of medicines, provides a quinoline compound for combined treatment of esophageal cancer, and particularly provides an application of a compound I or a pharmaceutically acceptable salt thereof and a second therapeutic agent to preparation of a medicine for treating esophageal cancer, and a combined medicine composition for treating esophageal cancer. The quinoline compound comprises (i) a compound I or a pharmaceutically acceptable salt thereof; and (ii) one or more second therapeutic agents, wherein the chemical name of compound I is 1- [[[4-(4-fluoro-2-methyl-1H-indole-5-yl) oxy-6-methoxyquinoline-7-yl]oxy]methyl] cyclopropylamine.

Description

technical field [0001] The invention belongs to the field of medicine, and the invention belongs to the technical field of pharmaceutical preparations, in particular to a quinoline compound or a pharmaceutically acceptable salt thereof for combined treatment of esophageal cancer. Background technique [0002] Esophageal cancer (EC) is a common malignant tumor formed by the abnormal proliferation of esophageal squamous epithelium or glandular epithelium, accounting for 2% of all malignant tumors, and about 400,000 to 500,000 people die of esophageal cancer every year worldwide. . The etiology of esophageal cancer is related to the chronic stimulation of nitrosamines, inflammation and trauma, genetic factors and the content of trace elements in drinking water, grain and vegetables. Smoking and drinking are common causes of esophageal cancer, and China is a high-incidence area of ​​esophageal cancer. China is one of the countries with a high incidence of esophageal cancer in t...

Claims

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Application Information

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IPC IPC(8): A61K31/4709A61K31/7048A61K31/337A61K33/24A61P35/00
CPCA61K31/4709A61K31/7048A61K31/337A61K33/24A61P35/00A61K2300/00
Inventor 王善春王峰
Owner CHIA TAI TIANQING PHARMA GRP CO LTD
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