Hyaluronan as a chemo-sensitizer in the treatment of cancer

Abstract

This application provides methods and compositions for the treatment of cancer. The application provides compositions comprising hyaluronic acid and a chemotherapeutic agent such as irinotecan that are useful in the treatment of cancer.

1 - 58 . (canceled) 
     
     
         59 . A method of treating a solid tumor cancer comprising the step of intravenously administering to a subject, with said solid tumor cancer, in need thereof, a therapeutically effective amount of a composition comprising a cancer chemotherapeutic and a hyaluronan, wherein the hyaluronan has a size expressed as a molecular weight of 800,000 to 1,432,000 Daltons or an intrinsic viscosity of 10.0 dl/gm to 14.5 dl/gm, and wherein said solid tumor cancer is CD44 receptor positive. 
     
     
         60 . The method according to  claim 59 , wherein the subject is a mammal. 
     
     
         61 . The method according to  claim 60 , wherein the mammal is selected from the group consisting of bovine, canine, equine, feline, porcine and human. 
     
     
         62 . The method according to  claim 59 , wherein the cancer chemotherapeutic agent is selected from the group consisting of carmustine (BCNU), chlorambucil (Leukeran), cisplatin (Platinol), Cytarabine, doxorubicin (Adriamycin), fluorouracil (5-FU), methotrexate (mexate), CPT 11 (irinotecan), etoposide, pliamycin (Mithracin) and taxanes. 
     
     
         63 . The method according to  claim 62 , wherein the cancer chemotherapeutic agent is fluorouracil (5-FU). 
     
     
         64 . The method according to  claim 62 , wherein the cancer chemotherapeutic agent is cisplatin. 
     
     
         65 . The method according to  claim 64 , wherein said cancer is selected from the group consisting of cancers of the lung. 
     
     
         66 . The method according to  claim 59 , wherein said cancer is selected from the group consisting of cancers of the lung or colorectal. 
     
     
         67 . The method according to  claim 59 , wherein said cancer is a pancreatic cancer. 
     
     
         68 . The method of  claim 59 , wherein said cancer is metastatic. 
     
     
         69 . The method of  claim 59 , wherein the molecular weight of the hyaluronan is about 800,000 to 1,000,000 Daltons. 
     
     
         70 . The method of  claim 59 , wherein the molecular weight of the hyaluronan is about 825,000 to 850,000 Daltons. 
     
     
         71 . The method according to  claim 59 , wherein the hyaluronan has a size expressed as an intrinsic viscosity of 10.0 dl/gm to 14.5 dl/gm. 
     
     
         72 . The method of  claim 59 , wherein said hyaluronan is administered at a dose of about 750 to 1500 mg/m 2 . 
     
     
         73 . The method of  claim 59 , where said hyaluronan is administered at a dose of about 900 to 1100 mg/m 2 . 
     
     
         74 . A method of treating a subject with a solid tumor cancer comprising the administration intravenously of a composition comprising a therapeutically effective amount of irinotecan (CPT 11) together with hyaluronan, wherein the hyaluronan has a size expressed as a molecular weight of 800,000 to 1,432,000 Daltons or an intrinsic viscosity of 10.0 dl/gm to 14.5 dl/gm, to a subject with said solid tumor cancer in need of such treatment, wherein said solid tumor cancer is CD44 receptor positive. 
     
     
         75 . The method according to  claim 74 , wherein the subject is a mammal. 
     
     
         76 . The method according to  claim 75 , wherein the mammal is selected from the group consisting of bovine, canine, equine, feline, porcine and human. 
     
     
         77 . The method of  claim 74 , wherein said cancer is metastatic. 
     
     
         78 . The method according to  claim 74 , wherein said cancer is selected from the group consisting of cancers of the lung. 
     
     
         79 . The method according to  claim 74 , wherein said cancer is a pancreatic cancer. 
     
     
         80 . The method according to  claim 74 , wherein said cancer is colorectal cancer. 
     
     
         81 . The method of  claim 80 , wherein the molecular weight of the hyaluronan is about 800,000 to 950,000 Daltons at a dose of about 250 mg/m 2  to about 5000 mg/m 2  and an effective amount of irinotecan (CPT 11) at a dose of about 125 mg/m 2  to 350 mg/m 2 , 
     
     
         82 . The method of  claim 80 , wherein said hyaluronan has a molecular weight of about 825,000 to 850,000 Daltons. 
     
     
         83 . The method of  claim 80 , wherein said hyaluronan is administered at a dose of about 500 to 1500 mg/m 2 . 
     
     
         84 . The method of  claim 80 , where said hyaluronan is administered at a dose of about 900 to 1100 mg/m 2 . 
     
     
         85 . The method of  claim 80 , wherein said hyaluronan is administered at a dose of about 1000 mg/m 2 . 
     
     
         86 . The method of  claim 74 , wherein the molecular weight of the hyaluronan is about 800,000 to 1,000,000 Daltons. 
     
     
         87 . The method of  claim 74 , wherein the molecular weight of the hyaluronan is about 825,000 to 850,000 Daltons. 
     
     
         88 . The method according to  claim 74 , wherein the hyaluronan has a size expressed as an intrinsic viscosity of 10.0 dl/gm to 14.5 dl/gm. 
     
     
         89 . The method of  claim 74 , wherein said hyaluronan is administered at a dose of about 750 to 1500 mg/m 2 . 
     
     
         90 . The method of  claim 74 , where said hyaluronan is administered at a dose of about 900 to 1100 mg/m 2 . 
     
     
         91 . The method of  claim 74 , wherein the dose of irinotecan is from about 125 to about 350 mg/m 2 . 
     
     
         92 . The method of  claim 74 , wherein the dose of irinotecan is from about 100 to about 200 mg/m 2 .