Method of treating multiple myeloma using 17-AAG or 17-AG or a prodrug of either in combination with a proteasome inhibitor
First Claim
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1. A method of treating multiple myeloma (MM) in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of 17-allylamino-17-demethoxy-geldanamycin (17-AAG) or 17-aminogeldanamycin (17-AG) or a prodrug of either 17-AAG or 17-AG, and a therapeutically effective dose of a proteasome inhibitor, and optionally repeating said step until no further therapeutic benefit is obtained.
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Abstract
A method for treating multiple myeloma in a subject by administering to the subject 17-allylamino-17-demethoxy-geldanamycin or 17-amino geldanamycin, or a pro drug of either 17-AAG or 17-AG, in combination with a proteasome inhibitor.
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45 Claims
- 1. A method of treating multiple myeloma (MM) in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of 17-allylamino-17-demethoxy-geldanamycin (17-AAG) or 17-aminogeldanamycin (17-AG) or a prodrug of either 17-AAG or 17-AG, and a therapeutically effective dose of a proteasome inhibitor, and optionally repeating said step until no further therapeutic benefit is obtained.
- 2. A method of treating MM in a subject in need of such treatment, comprising the step of administering multiple doses of 17-AAG or 17-AG or a prodrug of either to said subject over a time period of at least 2 weeks, wherein each such dose is in the range of about 100 to about 340 mg/m2 of 17-AAG, or an equivalent amount of 17-AG or a 17-AAG prodrug or 17-AG prodrug, and multiple doses of a proteasome inhibitor, wherein said proteasome inhibitor is bortezomib and each such dose is at least about 1 mg/m2.
- 7. A method of treating MM in a subject in need of such treatment, comprising the step of administering a therapeutically effective dose of a proteasome inhibitor and a therapeutically effective dose of 17-AAG or a prodrug of 17-AAG that results in an AUCtotal of 17-AAG per dose in the range of about 2,300 to about 19,000 ng/mL*h.
- 13. A method of treating MM in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of a proteasome inhibitor and a therapeutically effective dose of 17-AG or a prodrug of 17-AG that results in an AUCtotal of 17-AG per dose in the range of about 800 to about 17,000 ng/mL*h.
- 19. A method of treating MM in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of a proteasome inhibitor and a therapeutically effective dose of 17-AAG, a prodrug of 17-AAG, 17-AG, or a prodrug of 17-AG that results in a combined AUCtotal of 17-AAG and 17-AG per dose in the range of about 3,500 to about 35,000 ng/mL*h.
- 25. A method of treating MM in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of a proteasome inhibitor and a therapeutically effective dose of 17-AAG or a prodrug of 17-AAG that results in a Terminal T1/2 of 17-AAG in the range of 1.6 h to 5.6 h.
- 27. A method of treating MM in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of a proteasome inhibitor and a therapeutically effective dose of 17-AG or a prodrug of 17-AG that results in a Terminal T1/2 of 17-AG in the range of 3.7 h to 9.1 h.
- 29. A method of treating MM in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of a proteasome inhibitor and a therapeutically effective dose of 17-AAG or a prodrug of 17-AAG that results in a Volume of distribution VZ of 17-AAG in the range of 56 L to 250 L.
- 31. A method of treating MM in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of a proteasome inhibitor and a therapeutically effective dose of 17-AAG or a prodrug of 17-AAG that results in a Clearance of 17-AAG in the range of 13 to 85 L/h.
- 33. A method of treating MM in a subject in need of such treatment, comprising the step of administering to said subject a therapeutically effective dose of a proteasome inhibitor and a therapeutically effective dose of 17-AAG or a prodrug of 17-AAG that results in a Volume of distribution VSS of 17-AAG in the range of 96 to 250 L.
Specification