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, 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 non-small cell lung cancer (NSCLC) in a human individual comprising administering to the individual:
a) an effective amount of a composition comprising nanoparticles comprising paclitaxel coated with albumin, and
b) an effective amount of a platinum-based agent, wherein the platinum-based agent is cisplatin or carboplatin, and wherein the nanoparticle composition is free of cremophor.
2. The method according to claim 1 , wherein said platinum-based agent is carboplatin.
3. The method according to claim 1 , wherein the composition comprising nanoparticles comprising paclitaxel coated with albumin and the platinum-based agent are administered simultaneously.
4. The method according to claim 1 , wherein the composition comprising nanoparticles comprising paclitaxel coated with albumin and the platinum-based agent are administered sequentially.
5. The method according to claim 1 , wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm.
6. The method according to claim 5 , wherein the weight ratio of the albumin and paclitaxel in the nanoparticle composition is less than about 9:1.
7. The method according to claim 5 , wherein the platinum-based agent is carboplatin.
8. The method according to claim 1 , wherein the albumin is human serum albumin.
9. The method of claim 1 , wherein the cancer is an advanced stage cancer.
10. The method of claim 1 , wherein the dosage of paclitaxel in the nanoparticle composition is about 50 to about 400 mg/m 2 .
11. The method of claim 1 , wherein the nanoparticle composition is administered on a three week schedule and the dosage of paclitaxel in the nanoparticle composition is in the range of 100-400 mg/m 2 .
12. The method of claim 1 , wherein the nanoparticle composition is administered on a weekly schedule and the dosage of paclitaxel in the nanoparticle composition is in the range of 50-250 mg/m 2 .
13. The method of claim 1 , wherein the nanoparticle composition is administered on a three week schedule and the dosage of paclitaxel in the nanoparticle composition is in the range of 220-340 mg/m 2 .
14. The method of claim 13 , wherein the platinum-based agent is carboplatin.
15. The method of claim 1 , wherein the nanoparticle composition is administered on a weekly schedule and the dosage of paclitaxel in the nanoparticle composition is in the range of 100-150 mg/m 2 .
16. The method of claim 1 , wherein the interval between each administration of the nanoparticle composition is no more than about a week.
17. The method of claim 1 , wherein the weight ratio of the albumin and paclitaxel in the nanoparticle composition is about 18:1 or less.
18. The method of claim 5 , wherein the weight ratio of the albumin and paclitaxel in the nanoparticle composition is about 18:1 or less.
19. The method of claim 5 , wherein the weight ratio of albumin and paclitaxel in the nanoparticle composition is about 9:1 or less.
20. The method of claim 15 , wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm.
21. The method of claim 20 , wherein the weight ratio of albumin and paclitaxel in the nanoparticle composition is about 18:1 or less.
22. The method of claim 21 , wherein the weight ratio of albumin and paclitaxel in the nanoparticle composition is about 9:1 or less.
23. The method of claim 22 , wherein the weight ratio of albumin and paclitaxel in the nanoparticle composition is less than about 9:1.
24. The method of claim 19 , wherein the platinum-based agent is carboplatin, and wherein the albumin is human serum albumin.
25. The method of claim 15 , wherein the cancer is an advanced stage cancer.
26. The method of claim 15 , wherein the dosage of paclitaxel in the nanoparticle composition is about 100 mg/m 2 .
27. The method of claim 26 , wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm.
28. The method of claim 27 , wherein the weight ratio of albumin and paclitaxel in the nanoparticle composition is about 18:1 or less.
29. The method of claim 28 , wherein the weight ratio of albumin and paclitaxel in the nanoparticle composition is about 9:1 or less.
30. The method of claim 29 , wherein the weight ratio of albumin and paclitaxel in the nanoparticle composition is less than about 9:1.
31. The method of claim 18 , wherein the platinum-based agent is carboplatin.
32. The method of claim 26 , wherein the cancer is an advanced stage cancer.
33. The method of claim 1 , wherein the platinum-based agent is cisplatin.
34. The method of claim 20 , wherein the platinum-based agent is carboplatin.