Combination therapy with an antitumor alkaloid

Abstract

The present invention relates to the combination of PM01183 with several anticancer drugs, in particular other anticancer drugs selected from antitumor platinum coordination complexes, antimetabolites, mitotic inhibitors, anticancer antibiotics, topoisomerase I and/or II inhibitors, proteasome inhibitors, histone deacetylase inhibitors, nitrogen mustard alkylating agents, nitrosourea alkylating agents, nonclassical alkylating agents, estrogen antagonists, androgen antagonists, mTOR inhibitors, tyrosine kinase inhibitors, and other agents selected from aplidine, ET-743, PM02734 and PM00104, and the use of these combinations in the treatment of cancer.

1 .- 38 . (canceled) 
     
     
         39 . A method of treating cancer comprising administering to a patient in need of such treatment an amount of PM01183, or a pharmaceutically acceptable salt thereof, with an amount of paclitaxel that together are therapeutically effective and wherein the cancer to be treated is ovarian cancer. 
     
     
         40 . The method of treating cancer according to  claim 39 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and paclitaxel form part of the same medicament. 
     
     
         41 . The method of treating cancer according to  claim 39 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and paclitaxel are provided as separate medicaments for administration at the same time or at different times. 
     
     
         42 . The method of treating cancer according to  claim 41 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and paclitaxel are provided as separate medicaments for administration at different times. 
     
     
         43 . The method of treating cancer according to  claim 39 , wherein the cancer is refractory to previous therapy. 
     
     
         44 . The method of treating cancer according to  claim 43 , wherein the patient is relapsing with progressive disease after previous treatment for ovarian cancer. 
     
     
         45 . The method of treating cancer according to  claim 39 , wherein the cancer is metastatic. 
     
     
         46 . The method of treating cancer according to  claim 39 , wherein the cancer is advanced. 
     
     
         47 . The method of treating cancer according to  claim 39 , wherein administration is every three to four weeks. 
     
     
         48 . The method of treating cancer according to  claim 47 , wherein administration is every three weeks. 
     
     
         49 . The method of treating cancer according to  claim 39 , wherein the dose of PM01183 administered in combination with paclitaxel in ovarian cancer is lower than an effective dose of PM01183 administered as a monotherapy in ovarian cancer. 
     
     
         50 . The method of treating cancer according to  claim 39 , wherein PM01183 is administered in synergistic combination with paclitaxel. 
     
     
         51 . The method of treating cancer according to  claim 39 , wherein the combination treatment increases the efficacy of the therapeutic effect for treating the ovarian cancer in said patient or minimizes or delays the development of drug resistance. 
     
     
         52 . A method of inhibiting cancer cell growth comprising contacting cancer cells with PM01183, or a pharmaceutically acceptable salt thereof, in synergistic combination with paclitaxel, wherein the cancer cells are ovarian cancer cells. 
     
     
         53 . method of increasing or potentiating the therapeutic efficacy of PM01183 monotherapy in the treatment of ovarian cancer, which comprises administering to a patient in need thereof a therapeutically effective amount of PM01183, or a pharmaceutically acceptable salt thereof, in conjunction with paclitaxel.