Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan

Abstract

Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin.

What is claimed is: 
     
         1 . A method of treating pancreatic cancer in a human patient, the method comprising intravenously administering to the patient once every two weeks an antineoplastic therapy comprising:
 a. a single administration of 80 mg/m 2  of the antineoplastic agent irinotecan encapsulated in a liposome, in combination with   b. a single administration of 200 mg/m 2  of (l) form of leucovorin, and   c. a single administration of 2400 mg/m 2  of the antineoplastic agent 5-fluorouracil to treat the pancreatic cancer in the patient,   
       wherein no other antineoplastic agent is administered to the patient during the two week administration period. 
     
     
         2 . The method of  claim 1 , wherein the leucovorin is administered as 400 mg/m 2  of the (l+d) racemic form of leucovorin. 
     
     
         3 . The method of  claim 1 , wherein each administration of irinotecan is administered as an intravenous infusion of irinotecan liposome over 90 minutes, followed by the administration of leucovorin over 30 minutes, followed by the intravenous infusion of 5-fluorouracil over 46 hours. 
     
     
         4 . The method of  claim 1 , wherein the pancreatic cancer has progressed in the human patient after treatment of the pancreatic cancer with a gemcitabine-based therapy prior to the administration of the irinotecan. 
     
     
         5 . The method of  claim 1 , wherein the antineoplastic therapy is administered for at least 6 weeks. 
     
     
         6 . A method of treating pancreatic cancer in a human patient, the method comprising administering to the patient an anti-neoplastic therapy once every two, the anti-neoplastic therapy consisting of:
 a. a single administration of 80 mg/m 2  of the antineoplastic agent irinotecan encapsulated in a liposome, over a 90 minute infusion, followed by   b. a single intravenous administration of 200 mg/m 2  of (l) form of leucovorin over 30 minutes, and   c. a single intravenous administration of 2400 mg/m 2  of the antineoplastic agent 5-fluorouracil over 46 hours,   
       to treat the pancreatic cancer in the patient. 
     
     
         7 . The method of  claim 5 , wherein the pancreatic cancer has progressed in the human patient after treatment of the pancreatic cancer with a gemcitabine-based therapy prior to the administration of the irinotecan. 
     
     
         8 . The method of  claim 6 , wherein the leucovorin is administered as 400 mg/m 2  of the (l+d) racemic form of leucovorin. 
     
     
         9 . The method of  claim 5 , wherein the leucovorin is administered as 400 mg/m 2  of the (l+d) racemic form of leucovorin. 
     
     
         10 . The method of  claim 5 , wherein 5-fluorouracil is administered following the leucovorin. 
     
     
         11 . The method of  claim 5 , wherein the antineoplastic therapy is administered over a total of 48 hours 
     
     
         12 . The method of  claim 10 , wherein the leucovorin is administered as 400 mg/m 2  of the (l+d) racemic form of leucovorin. 
     
     
         13 . The method of  claim 11 , wherein 5-fluorouracil is administered following the leucovorin. 
     
     
         14 . The method of  claim 6 , wherein the antineoplastic therapy is administered for at least 6 weeks. 
     
     
         15 . A method of treating pancreatic cancer in a human patient, the method consisting of administering to the patient over a total of 48 hours, repeated once every two weeks, an antineoplastic therapy comprising:
 a. a single administration of 80 mg/m 2  of the antineoplastic agent irinotecan encapsulated in a liposome, over a 90 minute infusion, followed by   b. a single intravenous administration of 200 mg/m 2  of (l) form of leucovorin over 30 minutes, followed by   c. a single intravenous administration of 2400 mg/m 2  of the antineoplastic agent 5-fluorouracil over 46 hours,   
       to treat the pancreatic cancer in the patient. 
     
     
         16 . The method of  claim 15 , wherein the antineoplastic therapy is administered for at least 6 weeks. 
     
     
         17 . The method of  claim 15 , wherein the leucovorin is administered as 400 mg/m 2  of the (l+d) racemic form of leucovorin. 
     
     
         18 . The method of  claim 15 , wherein the pancreatic cancer is metastatic adenocarcinoma of the pancreas that has progressed in the human patient after treatment of the pancreatic cancer with a gemcitabine-based therapy prior to the administration of the irinotecan. 
     
     
         19 . A method of treating pancreatic cancer in a human patient, the method comprising administering to the patient an antineoplastic therapy once every two weeks, the antineoplastic therapy consisting of administering in a single treatment cycle:
 a. a single administration of 80 mg/m 2  of the antineoplastic agent irinotecan encapsulated in a liposome, over a 90 minute infusion, followed by   b. a single administration of 200 mg/m 2  of (l) form of leucovorin over 30 minutes, followed by   c. a single administration of 2400 mg/m 2  of the antineoplastic agent 5-fluorouracil over 46 hours,   
       to treat the pancreatic cancer in the patient. 
     
     
         20 . The method of  claim 19 , wherein the antineoplastic therapy is administered for at least 6 weeks. 
     
     
         21 . The method of  claim 20 , wherein the 200 mg/m 2  of the (l) form of leucovorin is administered as 400 mg/m 2  of the (l+d) racemic form of leucovorin. 
     
     
         22 . The method of  claim 21 , wherein the pancreatic cancer is metastatic adenocarcinoma of the pancreas that has progressed in the human patient after treatment of the pancreatic cancer with a gemcitabine-based therapy prior to the administration of the irinotecan.