Methods for Treating Metastatic Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan and Oxaliplatin
Combination therapy regimens including liposomal irinotecan, oxaliplatin and 5-fluorouracil are useful in the treatment of pancreatic cancer, including treatment of patients diagnosed with previously untreated metastatic adenocarcinoma of the pancreas. The combination therapy can include the administration of liposomal irinotecan, oxaliplatin, leucovorin and 5-fluorouracil once every two weeks.
1 . A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has not previously received an antineoplastic agent to treat the metastatic adenocarcinoma of the pancreas, the method comprising administering an antineoplastic therapy to the patient a total of once every two weeks, the antineoplastic therapy consisting of administering to the patient a total of:
a. 60 mg/m 2 of liposomal irinotecan,
b. 60 or 85 mg/m 2 oxaliplatin,
c. 200 mg/m 2 of (l)-form of leucovorin or 400 mg/m 2 of the (l+d) racemic form of leucovorin, and
d. 2,400 mg/m 2 5-fluorouracil to treat the metastatic adenocarcinoma of the pancreas in the human patient.
2 . The method of claim 1 , wherein a total of 60 mg/m 2 oxaliplatin is administered to the patient during the antineoplastic therapy once every two weeks.
3 . The method of claim 1 , wherein a total of 85 mg/m 2 oxaliplatin is administered to the patient during the antineoplastic therapy once every two weeks.
4 . The method of claim 1 , wherein each administration of the oxaliplatin begins 2 hours after completing each administration of the liposomal irinotecan.
5 . The method of claim 1 , wherein the 5-fluorouracil is administered as an infusion over 46 hours.
6 . The method of claim 1 , wherein the leucovorin is administered immediately prior to the 5-fluorouracil.
7 . The method of claim 1 , wherein the liposomal irinotecan, oxaliplatin and leucovorin are administered on days 1 and 15 of a 28-day treatment cycle.
8 . The method of claim 1 , wherein the liposomal irinotecan is administered as an infusion over a total of about 90 minutes.
9 . The method of claim 1 , wherein the liposomal irinotecan is administered, followed by administering the oxaliplatin, followed by administering the leucovorin, followed by administering the 5-fluorouracil.
10 . The method of claim 1 , wherein the liposomal irinotecan comprises irinotecan sucrose octasulfate encapsulated in liposomes.
11 . The method of claim 1 , wherein the liposomal irinotecan comprises irinotecan encapsulated in liposome vesicles consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and a N-(carbonylmethoxypolyethlyene glycol-2000)-1,2-distearoly-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE).
12 . The method of claim 2 , wherein the liposomal irinotecan comprises irinotecan sucrose octasulfate encapsulated in liposomes, and the liposomal irinotecan comprises irinotecan encapsulated in liposome vesicles consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and a N-(carbonylmethoxypolyethlyene glycol-2000)-1,2-distearoly-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE).
13 . The method of claim 12 , wherein the liposomal irinotecan, oxaliplatin and leucovorin are administered on days 1 and 15 of a 28-day treatment cycle; each administration of the liposomal irinotecan is administered prior to the leucovorin; the leucovorin is administered immediately prior to each administration of the 5-fluorouracil and each administration of 5-fluorouracil is administered as an infusion over 46 hours.
14 . The method of claim 3 , wherein the liposomal irinotecan comprises irinotecan sucrose octasulfate encapsulated in liposomes, and the liposomal irinotecan comprises irinotecan encapsulated in liposome vesicles consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and a N-(carbonylmethoxypolyethlyene glycol-2000)-1,2-distearoly-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE).
15 . The method of claim 14 , wherein the liposomal irinotecan, oxaliplatin and leucovorin are administered on days 1 and 15 of a 28-day treatment cycle; each administration of the liposomal irinotecan is administered prior to the leucovorin; the leucovorin is administered immediately prior to each administration of the 5-fluorouracil and each administration of 5-fluorouracil is administered as an infusion over 46 hours.
16 . A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has not previously received gemcitabine to treat the metastatic adenocarcinoma of the pancreas, the method comprising administering an antineoplastic therapy to the patient a total of once every two weeks, the antineoplastic therapy consisting of administering to the patient a total of:
a. 60 mg/m 2 of liposomal irinotecan,
b. 85 mg/m 2 oxaliplatin,
c. 200 mg/m 2 of (l)-form of leucovorin or 400 mg/m 2 of the (l+d) racemic form of leucovorin, and
d. 2,400 mg/m 2 5-fluorouracil to treat the metastatic adenocarcinoma of the pancreas in the human patient.
17 . The method of claim 16 , wherein
a. the liposomal irinotecan comprises irinotecan sucrose octasulfate encapsulated liposome vesicles comprising 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and a N-(carbonylmethoxypolyethlyene glycol-2000)-1,2-distearoly-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE);
b. the liposomal irinotecan, oxaliplatin and leucovorin are administered on days 1 and 15 of a 28-day treatment cycle;
c. each administration of the liposomal irinotecan is administered prior to the leucovorin;
d. the leucovorin is administered immediately prior to each administration of the 5-fluorouracil; and
e. each administration of 5-fluorouracil is administered as an infusion over 46 hours.
18 . The method of claim 17 , wherein each administration of the oxaliplatin begins after completing each administration of the liposomal irinotecan, and the method further comprises administering a corticosteroid and anti-emetic to the patient prior to the antineoplastic therapy.
19 . A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has not previously received gemcitabine to treat the metastatic adenocarcinoma of the pancreas, the method comprising administering an antineoplastic therapy to the patient a total of once every two weeks, the antineoplastic therapy consisting of administering to the patient a total of:
a. 60 mg/m 2 of liposomal irinotecan,
b. 60 mg/m 2 oxaliplatin,
c. 200 mg/m 2 of (l)-form of leucovorin or 400 mg/m 2 of the (l+d) racemic form of leucovorin, and
d. 2,400 mg/m 2 5-fluorouracil to treat the metastatic adenocarcinoma of the pancreas in the human patient.
20 . The method of claim 19 , wherein
a. the liposomal irinotecan comprises irinotecan sucrose octasulfate encapsulated liposome vesicles comprising 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and a N-(carbonylmethoxypolyethlyene glycol-2000)-1,2-distearoly-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE);
b. the liposomal irinotecan, oxaliplatin and leucovorin are administered on days 1 and 15 of a 28-day treatment cycle;
c. each administration of the liposomal irinotecan is administered prior to the leucovorin;
d. the leucovorin is administered immediately prior to each administration of the 5-fluorouracil; and
e. each administration of 5-fluorouracil is administered as an infusion over 46 hours.