Combinations and modes of administration of therapeutic agents and combination therapy
The present invention provides combination therapy methods of treating proliferative diseases (such as cancer) comprising a first therapy comprising administering to an individual an effective amount of a taxane in a nanoparticle composition, and a second therapy which may include, for example, radiation, surgery, administration of chemotherapeutic agents (such as an anti-VEGF antibody), or combinations thereof. Also provided are methods of administering to an individual a drug taxane in a nanoparticle composition based on a metronomic dosing regime.
1. A method of treating melanoma in a human individual, comprising administering to the individual: a) an effective amount of a composition comprising nanoparticles comprising taxane coated with albumin, wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm, and b) an effective amount of an anti-VEGF antibody, wherein the effective amount of the taxane in the composition is about 60 mg/m 2 to about 300 mg/m 2 .
2. The method of claim 1 , wherein the effective amounts of the nanoparticle composition and the anti-VEGF antibody synergistically inhibit cell proliferation.
3. The method of claim 1 , wherein the anti-VEGF antibody is bevacizumab.
4. The method of claim 3 , wherein the taxane is paclitaxel.
5. The method of claim 4 , wherein the weight ratio of the albumin and the taxane in the nanoparticle composition is about 1:1 to about 9:1.
6. The method of claim 5 , wherein the nanoparticle composition and the anti-VEGF antibody are administered intravenously.
7. The method of claim 6 , wherein the effective amount of the anti-VEGF antibody is about 10 mg/kg.
8. The method of claim 7 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
9. The method of claim 8 , wherein the nanoparticle composition is administered weekly.
10. The method of claim 9 , wherein the anti-VEGF antibody is administered once every two weeks.
11. The method of claim 10 , wherein the melanoma is metastatic melanoma.
12. The method of claim 5 , wherein the effective amount of the anti-VEGF antibody is greater than about 1 mg/kg to about 15 mg/kg.
13. The method of claim 1 , wherein the nanoparticle composition and the anti-VEGF antibody are administered sequentially to the individual.
14. The method of claim 1 , wherein the nanoparticle composition is administered for at least one cycle prior to the administration of the anti-VEGF antibody.
15. The method of claim 14 , wherein the administration of the nanoparticle composition is followed by the administration of an anti-VEGF antibody for at least about 3 weeks.
16. The method of claim 1 , wherein the taxane is paclitaxel.
17. The method of claim 16 , wherein the weight ratio of the albumin and the taxane in the nanoparticle composition is about 1:1 to about 9:1.
18. The method of claim 17 , wherein the nanoparticle composition and the anti-VEGF antibody are administered intravenously.
19. The method of claim 18 , wherein the effective amount of the anti-VEGF antibody is about 10 mg/kg.
20. The method of claim 19 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
21. The method of claim 20 , wherein the nanoparticle composition is administered weekly.
22. The method of claim 21 , wherein the anti-VEGF antibody is administered once every two weeks.
23. The method of claim 22 , wherein the melanoma is metastatic melanoma.
24. The method of claim 16 , wherein the nanoparticle composition and the anti-VEGF antibody are administered intravenously.
25. The method of claim 24 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 15 mg/kg.
26. The method of claim 24 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
27. The method of claim 16 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 20 mg/kg.
28. The method of claim 27 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
29. The method of claim 16 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
30. The method of claim 29 , wherein the melanoma is metastatic melanoma.
31. The method of claim 16 , wherein the melanoma is metastatic melanoma.
32. The method of claim 1 , wherein the weight ratio of the albumin and the taxane in the nanoparticle composition is about 1:1 to about 9:1.
33. The method of claim 1 , wherein the nanoparticle composition is free of Cremophor.
34. The method of claim 1 , wherein the nanoparticle composition is administered weekly.
35. The method of claim 34 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
36. The method of claim 1 , wherein the nanoparticle composition is administered prior to the anti-VEGF antibody.
37. The method of claim 1 , wherein the anti-VEGF antibody is administered prior to the nanoparticle composition.
38. The method of claim 1 , wherein the nanoparticle composition and the anti-VEGF antibody are administered intravenously.
39. The method of claim 1 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 20 mg/kg.
40. The method of claim 1 , wherein the effective amount of the taxane in in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
41. The method of claim 1 , wherein the melanoma is metastatic melanoma.
42. A method of inhibiting tumor metastasis in an individual having melanoma, comprising administering to the individual: a) an effective amount of a composition comprising nanoparticles comprising taxane coated with albumin, wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm, and b) an effective amount of an anti-VEGF antibody, wherein the effective amount of the taxane in the composition is about 60 mg/m 2 to about 300 mg/m 2 .
43. The method of claim 42 , wherein the effective amounts of the nanoparticle composition and the anti-VEGF antibody synergistically inhibit tumor metastasis.
44. The method of claim 42 , wherein the tumor metastasis is metastasis to lymph node.
45. The method of claim 42 , wherein the tumor metastasis is metastasis to the lung.
46. The method of claim 42 , wherein at least about 40% of metastasis is inhibited.
47. The method of claim 42 , wherein at least about 80% of metastasis is inhibited.
48. The method of claim 42 , wherein the nanoparticle composition is administered weekly.
49. The method of claim 48 , wherein the effective amount of the taxane in in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
50. The method of claim 42 , wherein the nanoparticle composition is administered prior to the anti-VEGF antibody.
51. The method of claim 42 , wherein the anti-VEGF antibody is administered prior to the nanoparticle composition comprising.
52. The method of claim 42 , wherein the taxane is paclitaxel.
53. The method of claim 52 , wherein the anti-VEGF antibody is bevacizumab.
54. The method of claim 53 , wherein the weight ratio of the albumin and the taxane in the nanoparticle composition is about 1:1 to about 9:1.
55. The method of claim 54 , wherein the nanoparticle composition and the anti-VEGF antibody are administered intravenously.
56. The method of claim 55 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 15 mg/kg.
57. The method of claim 54 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 15 mg/kg.
58. The method of claim 52 , wherein the weight ratio of the albumin and the taxane in the nanoparticle composition is about 1:1 to about 9:1.
59. The method of claim 58 , wherein the nanoparticle composition and the anti-VEGF antibody are administered intravenously.
60. The method of claim 59 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 15 mg/kg.
61. The method of claim 52 , wherein the nanoparticle composition and the anti-VEGF antibody are administered intravenously.
62. The method of claim 61 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 15 mg/kg.
63. The method of claim 61 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
64. The method of claim 52 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 20 mg/kg.
65. The method of claim 64 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
66. The method of claim 52 , wherein the effective amount of the taxane in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
67. The method of claim 66 , wherein the melanoma is metastatic melanoma.
68. The method of claim 52 , wherein the melanoma is metastatic melanoma.
69. The method of claim 42 , wherein the weight ratio of the albumin and the taxane in the nanoparticle composition is about 1:1 to about 9:1.
70. The method of claim 42 , wherein the nanoparticle composition and the anti-VEGF antibody are administered intravenously.
71. The method of claim 42 , wherein the effective amount of the anti-VEGF antibody is about 1 mg/kg to about 20 mg/kg.
72. The method of claim 42 , wherein the effective amount of the taxane in in the nanoparticle composition is about 80 mg/m 2 to about 150 mg/m 2 .
73. The method of claim 42 , wherein the melanoma is metastatic melanoma.
74. A kit comprising: a) a composition comprising nanoparticles comprising a taxane coated with albumin, wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm, b) an anti-VEGF antibody, and c) instructions for administering an effective amount of the nanoparticles and the anti-VEGF antibody to a human individual for treatment of melanoma, wherein the effective amount of the taxane in the composition is about 60 mg/m 2 to about 300 mg/m 2 .
75. The kit of claim 25 , wherein the taxane is paclitaxel.
76. The kit of claim 75 , wherein the weight ratio of the albumin and the taxane in the nanoparticle composition is about 1:1 to about 9:1.
77. The kit of claim 75 , wherein the anti-VEGF antibody is bevacizumab.