TREATMENT OF PANCREATIC CANCER WITH LIPOSOMAL IRINOTECAN
A liposome-encapsulated formulation of irinotecan can be used for the treatment of pancreatic cancer in combination with 5-fluorouracil and leucovorin, including treatment of patients diagnosed with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine.
1 . A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has previously been treated with the antineoplastic agent gemcitabine and has a baseline CA 19-9 level of at least 1,540 U/mL, the method comprising intravenously administering to the patient once every two weeks, an antineoplastic therapy consisting of: 80 mg/m 2 of the antineoplastic agent MM-398 liposomal irinotecan in combination with 200 mg/m 2 of (l)-form of leucovorin and 2,400 mg/m 2 of the antineoplastic agent 5-fluorouracil to treat the metastatic adenocarcinoma of the pancreas in the human patient.
2 . The method of claim 1 , wherein the patient has a baseline CA 19-9 level of from about 1542 U/mL to about 12,815 U/mL.
3 . The method of claim 1 , wherein the patient has a baseline CA 19-9 level of 12,815 U/mL or more.
4 . The method of claim 1 , wherein the 200 mg/m 2 of (l)-form of leucovorin is administered as 400 mg/m 2 of the (l+d) racemic form of leucovorin.
5 . The method of claim 1 , wherein the method comprises at least three cycles administered to the human patient for the metastatic adenocarcinoma of the pancreas.
6 . The method of claim 5 , wherein the MM-398 liposomal irinotecan, leucovorin and 5-fluorouracil are administered to the patient over 48 hours beginning on day 1 of a 2-week cycle.
7 . The method of claim 6 , wherein the 200 mg/m 2 of (l)-form of leucovorin is administered as 400 mg/m 2 of the (l+d) racemic form of leucovorin, and the leucovorin is administered to the patient prior to the 5-fluorouracil.
8 . The method of claim 7 , wherein the MM-398 liposomal irinotecan is administered to the patient prior to the leucovorin.
9 . The method of claim 8 , wherein the MM-398 liposomal irinotecan is administered as a 90 minute infusion, followed by administration of the leucovorin over 30 minutes, followed by administration of the 5-fluorouracil over 46 hours.
10 . A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has previously been treated with the antineoplastic agent gemcitabine and the patient has a baseline CA 19-9 level of at least 1542 U/mL, the method comprising intravenously administering to the patient once every two weeks, an antineoplastic therapy consisting of 80 mg/m 2 of the antineoplastic agent MM-398 liposomal irinotecan in combination with 200 mg/m 2 of (l)-form of leucovorin or 400 mg/m 2 of the (l+d) racemic form of leucovorin and 2,400 mg/m 2 of the antineoplastic agent 5-fluorouracil to treat the metastatic adenocarcinoma of the pancreas in the human patient, wherein the method comprises at least three cycles.
11 . The method of claim 10 , wherein the patient has a baseline CA 19-9 level of from about 1542 U/mL to about 12,815 U/mL.
12 . The method of claim 10 , wherein the patient has a baseline CA 19-9 level of at least about 12,815 U/mL.
13 . The method of claim 10 , wherein the leucovorin is administered as 400 mg/m 2 of the (l+d) racemic form of leucovorin.
14 . The method of claim 10 , wherein no other antineoplastic agent is administered to the human patient for treatment of the metastatic adenocarcinoma of the pancreas.
15 . The method of claim 14 , wherein the MM-398 liposomal irinotecan, leucovorin and 5-fluorouracil are administered to the patient over 48 hours beginning on day 1 of a 2-week cycle.
16 . The method of claim 15 , wherein 400 mg/m 2 of the (l+d) racemic form of leucovorin is administered to the patient prior to the 5-fluorouracil.
17 . The method of claim 16 , wherein the MM-398 liposomal irinotecan is administered to the patient prior to the leucovorin.
18 . The method of claim 17 , further comprising pre-medicating the patient with dexamethasone and a 5-HT3 antagonist or other anti-emetic prior to administering the MM-398 liposomal irinotecan.
19 . A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has previously been treated with the antineoplastic agent gemcitabine and has a baseline CA 19-9 level of less than 120 U/mL, the method comprising intravenously administering to the patient once every two weeks, 80 mg/m 2 of the antineoplastic agent MM-398 liposomal irinotecan in combination with 200 mg/m 2 of (l)-form of leucovorin or 400 mg/m 2 of the (l+d) racemic form of leucovorin and 2,400 mg/m 2 of the antineoplastic agent 5-fluorouracil to treat the metastatic adenocarcinoma of the pancreas in the human patient.
20 . The method of claim 19 , wherein the 200 mg/m 2 of (l)-form of leucovorin is administered as 400 mg/m 2 of the (l+d) racemic form of leucovorin.