Methods for reducing toxicity of a chemotherapeutic drug

Abstract

This disclosure relates to methods for improving the therapeutic index of a chemotherapeutic drug in the treatment of patients afflicted with cancer, by reducing chemotherapy-related toxicity to a level that allows the chemotherapeutic drug to be used in humans.

1 - 11 . (canceled) 
     
     
         12 . A method of reducing chemotherapy drug-related toxicity in a patient having cancer, which method comprises treating said patient with a complex comprising a therapeutically effective amount of a chemotherapy drug with an albumin carrier, and an effective amount of antibody which has specificity to an antigen on said cancer, wherein said antibodies populate the surface of said complex and retain binding specificity, wherein the chemotherapy drug has an unacceptable therapeutic index when administered alone, such that said patient has reduced risk of chemotherapy drug-related toxicity. 
     
     
         13 . The method of  claim 12 , wherein the chemotherapy drug-related toxicity is selected from the group consisting of cardiotoxicity, nephrotoxicity, hepatotoxicity, pulmonary toxicity, dermatologic toxicity, and gastrointestinal toxicity. 
     
     
         14 - 20 . (canceled) 
     
     
         21 . The method of  claim 12 , wherein the complex further comprises an effective amount of paclitaxel to form said complex. 
     
     
         22 . The method of  claim 21 , where the amount of paclitaxel is a sub-therapeutic amount. 
     
     
         23 . The method of  claim 21 , wherein the amount of paclitaxel is between 0.1 mg/m 2  and 50 mg/m 2 . 
     
     
         24 . The method of  claim 21 , wherein the weight ratio of the albumin carrier and the paclitaxel of the complex is greater than about 9:1. 
     
     
         25 . The method of  claim 12 , wherein the average diameter of the complex is less than 1 micron. 
     
     
         26 . The method of  claim 12 , wherein the antibody is selected from the group consisting of ado-trastuzumab emtansine, alemtuzumab, bevacizumab, blinatumomab, brentuximab vedotin, cetuximab, denosumab, dinutuximab, ibritumomab tiuxetan, ipilimumab, nivolumab, obinutuzumab, ofatumumab, panitumumab, pembrolizumab, pertuzumab, rituximab, trastuzumab, any combination thereof, and any biosimilar thereof. 
     
     
         27 . The method of  claim 12 , wherein the antibody is an anti-CD20 antibody which has specificity to a CD20 antigen. 
     
     
         28 . The method of  claim 27 , wherein the antibody is rituximab. 
     
     
         29 . The method of  claim 12 , wherein the complex further comprises a therapeutic agent. 
     
     
         30 . The method of  claim 29 , wherein the therapeutic agent is an antibiotic, an antimicrobial, an anti-inflammatory agent, or any combination thereof. 
     
     
         31 . The method of  claim 12 , wherein the chemotherapy drug is selected from the group consisting of abiraterone, bendamustine, bortezomib, carboplatin, cabazitaxel, cisplatin, chlorambucil, dasatinib, docetaxel, doxorubicin, epirubicin, erlotinib, etoposide, everolimus, gefitinib, idarubicin, imatinib, hydroxyurea, imatinib, lapatinib, leuprorelin, melphalan, methotrexate, mitoxantrone, nedaplatin, nilotinib, oxaliplatin, paclitaxel, pazopanib, pemetrexed, picoplatin, romidepsin, satraplatin, sorafenib, vemurafenib, sunitinib, teniposide, triplatin, vinblastine, vinorelbine, vincristine, cyclophosphamide, and any combination thereof. 
     
     
         32 . The method of  claim 12 , wherein the albumin carrier comprises ovalbumin, bovine serum albumin, human serum albumin, or any combination thereof. 
     
     
         33 . The method of  claim 12 , wherein the average diameter of the complex is between 0.1 μm and 0.9 μm. 
     
     
         34 . The method of  claim 12 , wherein at least 60 percent of complexes have a diameter between 0.1 μm and 0.9 μm. 
     
     
         35 . The method of  claim 12 , wherein the complex is administered intravenously. 
     
     
         36 . The method of  claim 12 , wherein the complex is administered with an effective amount of NK or NK-92 cells. 
     
     
         37 . The method of  claim 36 , wherein the NK or NK-92 cells are administered concurrently with the complex, sequentially to the complex, or a combination thereof. 
     
     
         38 . The method of  claim 12 , wherein a progression rate of the cancer is reduced by at least 5, at least 10, at least 25, at least 50, at least 75, or at least 100 percent.