METHOD OF TREATING PATIENTS NON-RESPONSIVE TO PALONOSETRON
A method for treating chemotherapy-induced nausea and vomiting in individuals undergoing chemotherapy and previously treated with, and whom failed to respond to, a 5-HT3 antagonist other than granisetron is described. Individuals who fail to respond to, for example, palonosetron, as evidenced by an inadequate prevention or attenuation of acute or delayed chemotherapy-induced nausea and vomiting, are treated with a semi-solid drug delivery vehicle that provides a sustained release of granisetron.
1 . A treatment method, comprising:
administering to a patient receiving chemotherapy, a semi-solid drug delivery vehicle comprising a bioerodible polymer and granisetron, wherein the patient was previously treated with a 5-HT 3 antagonist other than granisetron and failed to achieve a satisfactory prevention or reduction of acute or delayed chemotherapy-induced nausea and vomiting.
2 . The method of claim 1 , wherein the semi-solid drug delivery vehicle is administered subcutaneously.
3 . The method of claim 1 , where the patient that failed to achieve a satisfactory prevention or reduction of acute or delayed chemotherapy-induced nausea and vomiting was previously treated with palonosetron.
4 . The method of claim 3 , where the patient that failed to achieve a satisfactory prevention or reduction of acute or delayed chemotherapy-induced nausea and vomiting was previously treated with intravenously administered palonosetron.
5 . The method of claim 3 , wherein the patient is undergoing treatment for acute chemotherapy-induced nausea and vomiting.
6 . The method of claim 3 , wherein the patient is undergoing treatment for delayed onset chemotherapy-induced nausea and vomiting.
7 . The method of claim 5 , wherein the patient is receiving moderately emetogenic chemotherapy.
8 . The method of claim 5 , wherein the patient is receiving highly emetogenic chemotherapy.
9 . The method of claim 7 , comprising administering to the patient a single dose of the semi-solid drug delivery vehicle comprising from 1 to 25 mg of granisetron during one cycle of chemotherapy.
10 . The method of claim 9 , wherein the single dose of the semi-solid drug delivery vehicle comprises 5 or 10 mg of granisetron.
11 . The method of claim 9 , wherein the single dose is administered prior to commencement of chemotherapy.
12 . The method of claim 9 , wherein the single dose is administered post-chemotherapy.
13 . The method of claim 3 , wherein granisetron is the only anti-emetic agent comprised within the semi-solid drug delivery vehicle.
14 . The method of claim 3 , effective to provide a measurable prevention or reduction of acute or delayed chemotherapy-induced nausea and vomiting when compared to previous treatment with palonosetron.
15 . The method of claim 14 , effective to result in a complete absence of an emetic episode in the acute phase.
16 . The method of claim 14 , effective to result in a complete absence of an emetic episode in the delayed phase.
17 . The method of claim 14 , effective to result in a complete absence of an emetic episode in both the acute and delayed phase following chemotherapy.
18 . The method of claim 3 , wherein the administering is continued over one or more additional rounds of chemotherapy.
19 . The method of claim 1 , wherein the bioerodible polymer is a polyorthoester.
20 . The method of claim 19 , wherein the polyorthoester comprises subunits selected from
where
x is an integer selected from 1, 2, 3, and 4,
the total amount of p is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20,
s is an integer selected from 1, 2, 3, and 4,
the mole percentage of a-hydroxyacid containing subunits in the polyorthoester is from about 0.1 to about 25 mole percent,
and the polyorthoester has a molecular weight in a range of about 1000 to 10,000.
21 . The method of claim 1 , wherein the semi-solid drug delivery vehicle further comprises an excipient selected from polyethylene glycol ether derivatives having a molecular weight between about 200-4,000.
22 . The method of claim 21 , wherein the polyethylene glycol ether derivative is polyethylene glycol monomethyl ether 550.
23 . The method of claim 19 , wherein the semi-solid drug delivery vehicle comprises a polyorthoester, about 10-50 weight percent polyethylene glycol monomethyl ether having a molecular weight in a range of about 200 to 4,000, and about 1-5 weight percent granisetron.
24 . The method of claim 23 , wherein the polyorthoester is a reaction product of 3,9-di(ethylidene)-2,4,8,10-tetraoxaspiro[5.5]undecane (DETOSU), triethylene glycol and triethylene glycol diglycolide.
25 . The method of claim 24 , wherein the mole percentage of glycolide-containing subunits in the polyorthoester is from about 0.1 to about 25 mole percent.
26 . The method of claim 23 , wherein the semi-solid drug delivery vehicle comprises from about 70-80 weight percent polyorthoester, about 15-25 weight percent polyethylene glycol monomethyl ether and from 1 to 5 weight percent granisetron.