Method for cancer therapy

• US 6,548,531 B2
• Filed: 01/23/2002
• Issued: 04/15/2003
• Est. Priority Date: 02/09/2001
• Status: Expired due to Term

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Dhingra, Urvashi Hooda, Breimer, Lars Holger, Ritland, Steve, Dhingra, Kapil
• Primary Examiner(s): Reamer, James H.
• Application Number:
  US10/055,451
• Publication Number:
  US 20020156118A1
• Time in Patent Office: 447 Days
• Field of Search: 514/414
• US Class Current: 514/414
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Disclosed is a method of treating a patient suffering from cancer. The method comprises administering to a patient over a period of up to about 15 days a first component and a second component. The first component consists of a pharmaceutical composition containing as an active ingredient a compound of formula I or a pharmaceutically acceptable salt or ester of said compound. The second component consists of an injection solution containing as an active ingredient paclitaxel. The amount of each component in the combination is such that the combination is therapeutically effective. The components are administered concomitantly or sequentially in a three week to four week treatment cycle for as long as the tumor remains under control and the patient tolerates the regimen.

Claims

1. A method of treating a patient suffering form cancer, comprising administering to the patient a therapeutically effective amount of a combination of a first component consisting of pharmaceutical composition containing as an active ingredient a compound of formula I

a pharmaceutically acceptable salt or ester of said compound, wherein

R¹ is selected from the group consisting of —

H, —

CH₃, and —

CH₂OH, and

R² is —

CH₃;

and a second component consisting of paclitaxel.

2. The method of claim 1, wherein both components are administered concomitantly.

3. The method of claim 1, wherein both components are administered sequentially.

4. The method of claim 1 wherein the amount of compound of formula I in the combination is not by itself a therapeutically effective amount.

5. The method of claim 1 wherein the amount of paclitaxel I in the combination is not by itself a therapeutically effective amount.

6. The method of claim 1, wherein the pharmaceutical composition of the first component is an oral unit dosage form.

7. The method of claim 6, wherein the active ingredient of the first component is a compound of the formula:

or a pharmaceutically acceptable salt or ester thereof.

8. The method of claim 6, wherein the active ingredient of the first component is a compound of the formula

or a pharmaceutically acceptable salt or ester thereof.

9. The method of claim 6, wherein the active ingredient of the first component is a compound of the formula

or a pharmaceutically acceptable salt or ester thereof.

10. The method of claim 1 wherein the amount of a compound of formula I is from about 800 mg/m² to about 2988 mg/m² administered over a period of up to about 14 days.

11. The method of claim 10 wherein the amount of a compound of formula I is from about 1068 mg/m² to about 2988 mg/m².

12. The method of claim 11 wherein the amount of a compound of formula I is from about 1492 mg/m² to about 2348 mg/m².

13. The method of claim 1 wherein the amount of a compound of formula I is from about 800 mg/m² to about 2240 mg/m² administered over a period of up to about 4 days.

14. The method of claim 13 wherein the amount of a compound of formula I is from about 1120 mg/m² to about 1760 mg/m².

15. The method of claim 1 wherein the dose intensity of the compound of formula I is from about 267 mg/m²/week to about 747 mg/m²/week.

16. The method of claim 15 wherein the dose intensity of the compound of formula I is from about 373 mg/m²/week to about 587 mg/m²/week.

17. The method of claim 1 wherein the active ingredient of the second component is paclitaxel.

18. The method of claim 17 wherein the amount of paclitaxel is from about 135 mg/m² to about 250 mg/m² administered over a period of up to about 8 days.

19. The method of claim 18 wherein the amount of paclitaxel is from about 150 mg/m² to about 200 mg/m² administered over a period of up to about 8 days.

20. The method of claim 19 wherein the amount of paclitaxel is about 175 mg/m² administered over a period of up to about 8 days.

21. The method of claim 17 wherein the paclitaxel is administered on day 1 of a 21-day treatment cycle.

22. The method of claim 17 wherein the dose intensity of paclitaxel is from about 45 mg/m²/week to about 83 mg/m²/week.

23. The method of claim 22 wherein the dose intensity of paclitaxel is from about 50 mg/m²/week to about 67 mg/m²/week.

24. The method of claim 19 wherein the paclitaxel is administered on days 1 and 8 of a 21-28 day treatment cycle.

25. The method of claim 19 wherein the paclitaxel is administered on days 1, 8 and 15 of a 28-day treatment cycle.

35. The method of claim 1 comprising additionally subjecting the patient to radiotherapy.

26. A method of treating a patient suffering with cancer comprising administering to the patient:

(i) a first component consisting of pharmaceutical composition containing as an active ingredient a compound of formula;

 

or a pharmaceutically acceptable salt or ester of said compound,

wherein the compound of formula II is administered in an amount of from about 76 mg/m² per day to about 214 mg/m² per day for up to about 14 days starting on the first day of a 28 day cycle, and

(ii) a second component consisting of an injection solution containing as an active ingredient paclitaxel which is administered in amount of from about 135 mg/m² to about 250 mg/m² on the first day of a 28 day cycle, said 28 day cycle being repeated as long as the tumor remains under control.

27. A method of treating a patient suffering with cancer comprising administering to the patient:

(i) a first component consisting of pharmaceutical composition containing as an active ingredient a compound of formula;

 

or a pharmaceutically acceptable salt or ester of said compound,

wherein the compound of formula II is administered in an amount of from about 114 mg/m² per day to about 320 mg/m² per day for up to about 7 days starting on the first day of a 28 day cycle, and

(ii) a second component consisting of an injection solution containing as an active ingredient paclitaxel which is administered in amount of from about 150 mg/m² to about 200 mg/m² on the first day of a 28 day cycle, and said 28 day cycle being repeated as long as the tumor remains under control.

28. A method of treating a patient suffering with cancer comprising administering to the patient:

(i) a first component consisting of pharmaceutical composition containing as an active ingredient a compound of formula;

 

or a pharmaceutically acceptable salt or ester of said compound,

wherein the compound of formula II is administered in an amount of from about 200 mg/m² per day to about 560 mg/m² per day for up to about 4 days starting on the first day of a 21 day cycle, and

(ii) a second component consisting of an injection solution containing as an active ingredient paclitaxel which is administered in amount of from about 150 mg/m² to about 200 mg/m² on the first day of a 21 day cycle, and said 21 day cycle being repeated as long as the tumor remains under control.

29. A method of treating a patient suffering with cancer comprising administering to the patient:

(i) a first component consisting of pharmaceutical composition containing as an active ingredient a compound of formula;

 

or a pharmaceutically acceptable salt or ester of said compound,

wherein the compound of formula II is administered in an amount of from about 200 mg/m² per day to about 560 mg/m² per day for up to about 4 days starting on the first day of a 21 day cycle, and

(ii) a second component consisting of an injection solution containing as an active ingredient paclitaxel which is administered in amount of from about 67 mg/m² to about 125 mg/m² on the first and eighth day of a 21 day cycle, said 21 day cycle being repeated as long as the tumor remains under control.

30. A kit comprising:

(a) a first component containing one or more oral unit dosage forms of an active ingredient, each unit containing about 50 mg to about 200 mg of the active ingredient, wherein the active ingredient is a compound selected from formula I

 

or a pharmaceutically acceptable salt or ester said compound, wherein

R¹ is selected from the group consisting of —

H, —

CH₃, and —

CH₂OH, and

R² is —

CH₃; and

(b) a second component containing a vial or series of vials, each vial containing a single injectable solution dose or multiple injectable solution doses, each dose containing as an active ingredient about 30 mg to about 400 mg of paclitaxel.

31. The kit of claim 30, wherein the first component contains a sufficient number of units so that a patient can administer about 2 grams per day of the compound of formula I or a pharmaceutically acceptable salt or ester of said compound for a period of about 4 to about 14 days and the second component contains a sufficient number of doses so that a patient can administer about 400 mg per day of paclitaxel for a period of about three days.

32. The kit of claim 31 wherein the active ingredient of the first component is

33. The kit of claim 31, wherein the active ingredient of the first component is

34. The kit of claim 31, wherein the active ingredient of the first component is a compound of the formula