Cancer treatment with combination of plinabulin and taxane

Abstract

This invention provides a novel cancer treatment method in which plinabulin ( 1 -butyl-dehydrophenylahistin or NPI-2358) and a taxane compound (such as docetaxel) are used in combination. Our study has shown that the optimum combination of injecting plinabulin after taxane compound has unexpected enhanced efficacy in large tumor populations in animal model and in NSCLC cancer patients compared to taxane compound treatment alone. In addition, this optimum combination can achieve unexpected safety effect in lowering unbearable side effects of taxane compound, including decreasing its neutropenia rates at all grades and decreasing G-CSF use in cancer patients.

1 - 10 . (canceled) 
     
     
         11 . A method of treating a grade 3 or 4 neutropenia in a subject being administered 75 mg/m 2  docetaxel, comprising administering plinabulin at a dose of 10 to 50 mg/m 2  to the subject. 
     
     
         12 . The method of  claim 11 , comprising administering plinabulin prior to administering docetaxel. 
     
     
         13 . The method of  claim 12 , comprising administering plinabulin 2 h prior to administering docetaxel. 
     
     
         14 . The method of  claim 11 , comprising administering plinabulin after administering docetaxel. 
     
     
         15 . The method of  claim 14 , comprising administering plinabulin within 0.5 h to 72 h after administering docetaxel. 
     
     
         16 . The method of  claim 14 , comprising administering plinabulin within 0.5 h to 24 h after administering docetaxel. 
     
     
         17 . The method of  claim 14 , comprising administering plinabulin about 2 hours after administering docetaxel. 
     
     
         18 . The method of  claim 11 , wherein said administering results in a neutropenia rate lower than that induced by docetaxel alone. 
     
     
         19 . The method of  claim 11 , comprising administering plinabulin at a dose of 20 mg/m 2  to 30 mg/m 2 . 
     
     
         20 . The method of  claim 11 , comprising administering plinabulin at a dose of 20 mg/m 2  or 30 mg/m 2 . 
     
     
         21 . The method of  claim 11 , wherein the weight ratio of taxane dosage and plinabulin dosage is about 1.5:1 to 4:1. 
     
     
         22 . The method of  claim 11 , wherein the taxane-induced neutropenia rate is reduced by at least 4% for grade 3 neutropenia. 
     
     
         23 . The method of  claim 11 , wherein the taxane-induced neutropenia rate is reduced by at least 15% for grade 4 neutropenia. 
     
     
         24 . A method of treating cancer, comprising co-administering abraxane and plinabulin. 
     
     
         25 . The method of  claim 24 , wherein plinabulin is administered at least 1 hour after abraxane administration. 
     
     
         26 . The method of  claim 24 , wherein the cancer is selected from lung cancer, colon cancer, gastric cancer, liver cancer, breast cancer, prostate cancer, or multiple myeloma. 
     
     
         27 . A method of treating cancer in a patient having a tumor size of greater than 3 cm, comprising co-administering a taxane and plinabulin. 
     
     
         28 . The method of  claim 27 , wherein the plinabulin is administered at least 1 hour after taxane administration. 
     
     
         29 . The method of  claim 27 , wherein the patient has a tumor size of greater than 5 cm. 
     
     
         30 . The method of  claim 27 , wherein the patient has a tumor size of greater than 7 cm.