Methods of treating cancer

Abstract

The present invention provides methods and compositions for treating non-small-cell lung cancer (NSCLC) by administering a) a composition comprising nanoparticles that comprise paclitaxel and an albumin and b) a platinum-based agent (e.g., carboplatin). The present application also provides methods of treating prostate cancer by administering to the individual a) an effective amount of a composition comprising nanoparticles comprising docetaxel and an albumin; and b) an effective amount of a steroid.

1 . A method of treating NSCLC in an individual comprising administering to the individual a) an effective amount of a composition comprising nanoparticles comprising paclitaxel and an albumin and b) an effective amount of a platinum-based agent, wherein treatment is based upon the NSCLC having one or more characteristics selected from the group consisting of (i) differential levels of caveolin-1 (CAV1), (ii) differential levels of SPARC, (iii) differential levels of hypoxia markers, (iv) differential levels of tumor acidity, differential levels of gp60, (vi) differential levels of thymidylate synthase (TS), (vii) differential levels of S phase kinase-associated protein (Skp2), differential loss of heterozygosity (LOH) of single-nucleotide polymorphism (SNP), (ix) differential Kras mutations, differential methylation of promoter region of tumor-related genes, and (xi) differential albumin uptake. 
     
     
         2 . The method of  claim 1 , wherein the method comprises selecting the individual for treatment based on a characteristics selected from the group consisting of (i) differential levels of caveolin-1 (CAV1), (ii) differential levels of SPARC, (iii) differential levels of hypoxia markers, (iv) differential levels of tumor acidity, (v) differential levels of gp60, (vi) differential levels of thymidylate synthase (TS), (vii) differential levels of S phase kinase-associated protein (Skp2), (vii) differential loss of heterozygosity (LOH) of single-nucleotide polymorphism (SNP), (ix) differential Kras mutations, (x) differential methylation of promoter region of tumor-related genes, and (xi) differential albumin uptake. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the treatment is based on the NSCLC having a differential level of hypoxia. 
     
     
         5 . The method of  claim 4 , wherein the differential level of hypoxia is a differential level of carbonic anhydrase-9 (CA-9) or a differential level of LDH (e.g., LDH-5). 
     
     
         6 . The method of  claim 1 , wherein the treatment is based on the differential level of tumor acidity. 
     
     
         7 . The method of  claim 6 , wherein the differential level of tumor acidity is based on a differential level of HIF-1α, a differential level of HIF-2α, or a differential level of differentiated embryo-chrondrocyte expressed gene 1 (DEC-1). 
     
     
         8 . The method of  claim 1 , wherein the effective amount of the composition comprising nanoparticles comprising paclitaxel and albumin is between about 50 mg/m 2  and about 125 mg/m 2 . 
     
     
         9 . The method of  claim 1 , wherein the composition comprising nanoparticles comprising paclitaxel and albumin is administered weekly. 
     
     
         10 . The method of  claim 1 , wherein the effective amount of the platinum-based agent is between about AUC=2 and about AUC=6. 
     
     
         11 . The method of  claim 1 , wherein the platinum-based agent is administered once every three weeks. 
     
     
         12 . The method of  claim 1 , wherein the effective amount of the composition comprising nanoparticles comprising paclitaxel and albumin is 100 mg/m 2  administered weekly and the effective amount of the platinum-based agent is AUC=6 administered once every three weeks. 
     
     
         13 . The method of  claim 1 , wherein paclitaxel in the nanoparticles is coated with albumin. 
     
     
         14 . The method of  claim 1 , wherein the nanoparticles in the composition have an average diameter of no greater than about 200 nm. 
     
     
         15 . The method of  claim 1 , wherein the NSCLC is Stage IIIB NSCLC or Stage IV NSCLC. 
     
     
         16 . The method of  claim 1 , wherein the composition comprising nanoparticles comprising paclitaxel and albumin and the platinum-based agent are administered parenterally. 
     
     
         17 . The method of  claim 16 , wherein the composition comprising nanoparticles comprising paclitaxel and albumin and the platinum-based agent are administered intravenously. 
     
     
         18 . The method of  claim 1 , wherein the platinum-based agent is carboplatin. 
     
     
         19 . The method of  claim 1 , wherein the individual is human. 
     
     
         20 . The method of  claim 1 , wherein the method further comprises the administration of thoracic radiation. 
     
     
         21 . The method of  claim 20 , wherein the effective amount of the composition comprising nanoparticles comprising paclitaxel and albumin is between about 20 mg/m 2  to about 60 mg/m 2  administered weekly, the effective amount of a platinum-based agent is between about AUC=2 to about AUC=6 administered weekly, and the thoracic radiation is between about 25 to about 40 fractions by either 3D conformal or intensity-modulated techniques concurrently. 
     
     
         22 . A method of assessing whether an individual with NSCLC will respond to treatment comprising assessing one or more characteristics of the NSCLC selected from the group consisting of (a) differential levels of caveolin-1 (CAV1), (b) differential levels of SPARC, differential levels of hypoxia markers, (d) differential levels of tumor acidity, (e) differential levels of gp60, (f) differential levels of thymidylate synthase (TS), (g) differential levels of S phase kinase-associated protein (Skp2), (h) differential loss of heterozygosity (LOH) of single-nucleotide polymorphism (SNP), (i) differential Kras mutations, (j) differential methylation of promoter region of tumor-related genes, and (k) differential albumin uptake, wherein one or more of the characteristics of the NSCLC indicates the individual will be responsive to the treatment and the treatment comprises i) an effective amount of a composition comprising nanoparticles comprising paclitaxel and an albumin and ii) an effective amount of a platinum-based agent. 
     
     
         23 . A method of identifying an individual with NSCLC likely to respond to treatment comprising a) a composition comprising nanoparticles comprising paclitaxel and an albumin and b) a platinum-based agent comprising: (A) assessing one or more characteristics of NSCLC selected from the group consisting of (i) differential levels of caveolin-1 (CAV1), (ii) differential levels of SPARC, (iii) differential levels of hypoxia markers, (iv) differential levels of tumor acidity, (v) differential levels of gp60, (vi) differential levels of thymidylate synthase (TS), (vii) differential levels of S phase kinase-associated protein (Skp2), (viii) differential loss of heterozygosity (LOH) of single-nucleotide polymorphism (SNP), (ix) differential Kras mutations, differential methylation of promoter region of tumor-related genes, and (xi) differential albumin uptake; and (B) identifying the individual having one or more characteristics of NSCLC selected from the group consisting of (i) differential levels of caveolin-1 (CAV1), (ii) differential levels of SPARC, (iii) differential levels of hypoxia markers, (iv) differential levels of tumor acidity, (v) differential levels of gp60, (vi) differential levels of thymidylate synthase (TS), (vii) differential levels of S phase kinase-associated protein (Skp2), (viii) differential loss of heterozygosity (LOH) of single-nucleotide polymorphism (SNP), (ix) differential Kras mutations, (x) differential methylation of promoter region of tumor-related genes, and (xi) differential albumin uptake.