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NZ739270B2 - Therapeutic combinations of orally administered paclitaxel and a p-gp inhibitor for the treatment of cancer - Google Patents

Therapeutic combinations of orally administered paclitaxel and a p-gp inhibitor for the treatment of cancer Download PDF

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Publication number
NZ739270B2
NZ739270B2 NZ739270A NZ73927016A NZ739270B2 NZ 739270 B2 NZ739270 B2 NZ 739270B2 NZ 739270 A NZ739270 A NZ 739270A NZ 73927016 A NZ73927016 A NZ 73927016A NZ 739270 B2 NZ739270 B2 NZ 739270B2
Authority
NZ
New Zealand
Prior art keywords
paclitaxel
cancer
auc
administered
amount
Prior art date
Application number
NZ739270A
Other versions
NZ739270A (en
Inventor
Geralk J Fetterly
Paul William Glue
Cheung Tak Hung
Christopher Glyn Charles Alexander Jackson
E Douglas Kramer
Min Fun Rudolf Kwan
Original Assignee
Athenex Therapeutics Limited
Filing date
Publication date
Application filed by Athenex Therapeutics Limited filed Critical Athenex Therapeutics Limited
Priority claimed from PCT/IB2016/001132 external-priority patent/WO2017013490A2/en
Publication of NZ739270A publication Critical patent/NZ739270A/en
Publication of NZ739270B2 publication Critical patent/NZ739270B2/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/472Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia

Abstract

The application pertains to pharmaceutical combinations of orally administered paclitaxel and a P-gp inhibitor. The pharmaceutical combinations are suitable for the treatment of cancer in a subject and for reducing or preventing toxicity, hypersensitivity -type infusion reactions, and other negative outcomes resulting from or associated with intravenously administered paclitaxel (e.g., Taxol® or paclitaxel formulated with Cremophor®) therapy in a subject suffering from cancer.

Claims (49)

1. Use of a compound in the cture of a medicament for treatment of cancer in a subject in need thereof, wherein the subject is to be administered paclitaxel orally at an amount of about 100 mg/m2 to about 250 mg/m2 once a day and for 1-7 times a week; wherein the compound is Compound A: , wherein the medicament is ated to be administered to the subject at an amount of Compound A of about 15 mg, about 20 mg, about 25 mg, or about 30 mg once a day and for 1-7 times a week; and wherein Compound A is to be orally stered simultaneously with or prior to the paclitaxel.
2. Use of a compound in the manufacture of a medicament for reducing hematologic toxicity and/or neurotoxicity in a subject ing from cancer and undergoing paclitaxel therapy, wherein the subject is to be administered paclitaxel orally at an amount of about 100 mg/m2 to about 250 mg/m2 once a day and for 1-7 times a week; n the compound is Compound A: , wherein the medicament is formulated to administer Compound A to the subject at an amount of about 15 mg, about 20 mg, about 25 mg, or about 30 mg once a day and for 1-7 times a week; and wherein the plasma exposure of the orally administered paclitaxel, as measured by AUC(0?8), is equal to or greater than the plasma exposure, as measured by AUC(0?8), of enously administered paclitaxel at an amount of about 135 mg/m2 to 175 mg/m2 over a period of about 3 to about 24 hours once every 3 weeks, and wherein Compound A is to be orally administered simultaneously with or prior to the paclitaxel.
3. The use of claim 2, wherein the plasma re of the orally administered paclitaxel, as measured by AUC(0?8), is equal to or greater than the plasma re, as measured by AUC(0?8), of intravenously administered paclitaxel over a period of about 3 hours.
4. The use of claim 2, wherein the plasma exposure of the orally stered paclitaxel, as measured by AUC(0?8), is equal to or greater than the plasma exposure, as measured by AUC(0?8), of intravenously administered paclitaxel over a period of about 24 hours.
5. Use of a compound in the manufacture of a medicament for reducing or ting hypersensitivity-type infusion reactions associated with intravenously administered paclitaxel therapy in a subject suffering from cancer, wherein the subject is to be administered axel orally at an amount of about 100 mg/m2 to about 250 mg/m2 once a day and for 1-7 times a week; wherein the compound is Compound A: , wherein the medicament is to be administered to the subject at an amount of Compound A of about 15 mg, about 20 mg, about 25 mg, or about 30 mg once a day and for 1-7 times a week; and wherein the orally administered paclitaxel reac hes therapeutic blood or plasma levels in the subject, and n Compound A is to be orally administered simultaneously with or prior to the paclitaxel.
6. The use of any one of the preceding , wherein the paclitaxel is to be stered at an amount of about 150 mg/m2 to about 250 mg/m2.
7. The use of any one of claims 1 to 6, wherein the paclitaxel is to be administered at an amount of about 125 mg/m2 to about 250 mg/m2.
8. The use of any one of claims 1 to 6, wherein the paclitaxel is to be stered at an amount of about 125 mg/m2 to about 200 mg/m2.
9. The use of any one of claims 1 to 6, wherein the paclitaxel is to be stered at an amount of about 100 mg/m2 to about 250 mg/m2.
10. The use of any one of claims 1 to 6, wherein the paclitaxel is to be administered at an amount of about 100 mg/m2 to about 200 mg/m2.
11. The use of any one of the preceding claims, wherein the paclitaxel is to be administered at an amount of about 150 mg/m2.
12. The use of any one of the preceding claims, wherein the paclitaxel is to be administered at an amount of about 200 mg/m2.
13. The use of any one of claims 1 to 6, wherein the paclitaxel is to be administered at an amount of about 250 mg/m2.
14. The use of any one of the preceding claims, wherein the paclitaxel is to be administered 2-6 times per week.
15. The use of any one of the preceding claims, wherein the paclitaxel is to be administered 2-5 times per week.
16. The use of any one of the preceding claims, wherein the paclitaxel is to be stered at least twice per week.
17. The use of any one of the preceding , wherein the paclitaxel is to be administered at least 3 times per week.
18. The use of any one of the preceding claims, wherein the paclitaxel is to be administered at least 4 times per week.
19. The use of any one of the preceding claims, n the paclitaxel is to be administered 5 times per week.
20. The use of any one of the preceding claims, wherein the plasma exposure of the orally administered axel, as measured by AUC(0?8), is equal to or greater than the plasma re of intravenously administered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes, as measured by AUC(0?8).
21. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is greater than the 8) of intravenously administered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes.
22. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered axel is at least about 10% greater than the AUC(0?8) of intravenously administered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes.
23. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is at least about 20% greater than the AUC(0?8) of intravenously administered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes.
24. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is at least about 30% greater than the AUC(0?8) of intravenously administered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes.
25. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is at least about 40% r than the AUC(0?8) of paclitaxel intravenously administered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes.
26. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is at least about 50% r than the AUC(0?8) of paclitaxel enously stered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes.
27. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is at least about 80% greater than the AUC(0?8) of axel intravenously administered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes.
28. The use of any one of the preceding , wherein the AUC(0?8) of the orally administered paclitaxel is at least about 100% greater than the AUC(0?8) of paclitaxel intravenously administered axel at an amount of about 80 mg/m2 over a period of about 60 minutes.
29. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is about 2,000 ng•h/mL to about 10,000 L.
30. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is about 3,000 ng•h/mL to about 7,000 ng•h/mL.
31. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is about 5,000 ng•h/mL to about 7,000 ng•h/mL.
32. The use of any one of the preceding claims, wherein the total amount of the axel to be orally administered per week is about 300 mg/m2 to about 1,500 mg/m2.
33. The use of any one of the preceding claims, wherein the medicament is formulated for Compound A and the paclitaxel to be administered on the same day.
34. The use of any one of the preceding claims, wherein the AUC(0?8) of the orally administered paclitaxel is equal to or r than the AUC(0?8) of intravenously administered paclitaxel at an amount of about 80 mg/m2 over a period of about 60 minutes in treating cancer.
35. The use of any one of the preceding claims, wherein the subject is suffering from metastatic breast cancer, and wherein the plasma exposure of the orally stered axel, as measured by 8), is equal to or greater than the plasma exposure, as measured by AUC(0?8), of enously administered paclitaxel at an amount of about 260 mg/m2 over a period of about 30 minutes once every 3 weeks.
36. The use of any one of the ing claims, wherein the subject is suffering from ll cell lung cancer, and n the plasma exposure of the orally administered paclitaxel, as measured by AUC(0?8), is equal to or greater than the plasma exposure, as measured by AUC(0?8), of intravenously administered paclitaxel at an amount of about 100 mg/m2 over a period of about 30 minutes once per week for 3 weeks.
37. The use of any one of the preceding claims, wherein the subject is suffering from adenocarcinoma of the pancreas, and wherein the plasma exposure of the orally administered paclitaxel, as measured by AUC(0?8), is equal to or greater than the plasma exposure, as measured by AUC(0?8), of intravenously administered paclitaxel at an amount of about 125 mg/m2 over a period of about 30 minutes to about 40 minutes once per week for 3 weeks.
38. The use of any one of the ing claims, wherein the subject is suffering from carcinoma of the ovary, and wherein the plasma exposure of the orally administered axel, as ed by AUC(0?8), is equal to or greater than the plasma exposure, as measured by AUC(0?8), of intravenously administered paclitaxel at an amount of about 135 mg/m2 to about 175 mg/m2 over a period of about 3 hours once every 3 weeks.
39. The use of any one of the preceding claims, wherein the subject is suffering from carcinoma of the breast, and wherein the plasma re of the orally administered paclitaxel, as measured by AUC(0?8), is equal to or greater than the plasma exposure, as ed by AUC(0?8), of intravenously administered paclitaxel at an amount of about 175 mg/m2 once every 3 weeks.
40. The use of any one of the preceding claims, wherein the subject is suffering from nonsmall cell lung carcinoma, and wherein the plasma exposure of the orally administered paclitaxel, as measured by AUC(0?8), is equal to or greater than the plasma exposure, as measured by 8), of intravenously administered axel at an amount of about 135 mg/m2 over a period of about 24 hours once every 3 weeks.
41. The use of any one of the preceding claims, wherein the subject is suffering from AIDS- related Kaposi's Sarcoma, and wherein the plasma exposure of the orally administered paclitaxel, as measured by AUC(0?8), is equal to or r than the plasma exposure, as measured by AUC(0?8), of enously administered paclitaxel at an amount of about 135 mg/m2 over a period of about 3 hours once every 3 weeks, or at an amount of about 100 mg/m2 over a period of about 3 hours once every 2 weeks.
42. The use of any one of the preceding claims, wherein the cancer is ed from the group consisting of breast cancer, pancreatic cancer, non-small cell lung cancer, ovarian cancer, AIDS- related Kaposi sarcoma, esophageal cancer, ma, lymphoma, uterine cancer, peritoneal cancer, fallopian tube cancer, endometrial cancer, cervical cancer, thyroid cancer, gastric cancer, gastroesophageal junction cancer, urothelial cancer, bladder cancer, oropharynx cancer, hypopharynx cancer, larynx cancer, head and neck cancer, germ cell /tumors, prostate cancer, colon cancer, rectal cancer, kidney cancer, leukemia, and non-Hodgkin lymphoma.
43. The use of any one of the preceding claims, wherein the cancer is selected from the group consisting of breast cancer, pancreatic , non-small cell lung cancer, n cancer, AIDS- related Kaposi sarcoma, esophageal cancer, melanoma, lymphoma, uterine cancer, peritoneal cancer, fallopian tube , endometrial , cervical cancer, thyroid cancer, gastric cancer, gastroesophageal junction cancer, urothelial cancer, bladder , oropharynx cancer, hypopharynx cancer, larynx cancer, head and neck cancer, and germ cell cancer/tumors.
44. The use of any one of the ing claims, wherein the cancer is selected from the group consisting of breast cancer, all cell lung cancer, ovarian cancer, AIDS-related Kaposi sarcoma, esophageal cancer, bladder cancer, prostate cancer, and melanoma.
45. The use of any one of the preceding claims, wherein the cancer is selected from the group consisting of breast cancer, non-small cell lung cancer, ovarian cancer, and AIDS-related Kaposi sarcoma.
46. The use of any one of the preceding claims, wherein the ment is formulated for Compound A to be orally administered at an amount of about 15 mg.
47. The use of any one of the preceding , wherein Compound A is to be administered before the paclitaxel is to be administered.
48. The use of any one of the preceding claims, wherein the intravenously administered paclitaxel is paclitaxel in polyethoxylated castor oil.
49. The use of any one of claims 1 to 47, wherein the intravenously administered paclitaxel is protein-bound paclitaxel.
NZ739270A 2016-07-21 Therapeutic combinations of orally administered paclitaxel and a p-gp inhibitor for the treatment of cancer NZ739270B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562195243P 2015-07-21 2015-07-21
PCT/IB2016/001132 WO2017013490A2 (en) 2015-07-21 2016-07-21 Therapeutic combinations of orally administered paclitaxel and a p-gp inhibitor for the treatment of cancer

Publications (2)

Publication Number Publication Date
NZ739270A NZ739270A (en) 2024-10-25
NZ739270B2 true NZ739270B2 (en) 2025-01-28

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