Methods of treating bladder cancer

Patent metadata

Field	Value
Publication number	US-2016008330-A1
Application number	US-201414772725-A
Country	US
Kind code	A1
Filing date	Mar 13, 2014
Priority date	Mar 14, 2013
Publication date	Jan 14, 2016
Grant date	—

Abstract

The present invention provides methods and compositions for treating bladder cancer, including metastatic bladder cancer and non-muscle-invasive bladder cancer, by administering a composition comprising nanoparticles that comprise mTOR inhibitor and optionally an albumin.

First claim

1 . A method of treating bladder cancer in an individual, comprising administering to the individual an effective amount of a composition comprising nanoparticles comprising a limus drug and an albumin.

2 . The method of claim 1 , wherein the nanoparticle composition is administered intravesicularly.

3 . The method of claim 1 , wherein the bladder cancer is non-muscle-invasive bladder cancer.

4 . The method of claim 1 , wherein the bladder cancer is refractory to treatment with BCG, mitomycin C, or interferon.

5 . The method of claim 1 , wherein the nanoparticle composition is administered at least once weekly.

6 . The method of claim 1 , wherein the dose of limus drug in the nanoparticle composition is about 5 to about 500 mg.

7 . The method of claim 6 , wherein the dose of limus drug in the nanoparticle composition is about 30 to about 400 mg.

8 . The method of claim 6 , wherein the nanoparticle composition is administered at a volume of about 20 to about 150 ml.

9 . The method of claim 6 , wherein the nanoparticle composition is administered intravesicularly, and wherein the composition is retained in the bladder for about 30 minutes to about 4 hours.

10 . The method of claim 1 , further comprising administering an effective amount of a second therapeutic agent.

11 . The method of claim 10 , wherein the second therapeutic agent is an immunotherapeutic agent.

12 . The method of claim 11 , wherein the second therapeutic agent is BCG.

13 . The method of claim 12 , wherein the BCG is administered intravesicularly.

14 . The method of claim 13 , wherein the BCG is administered at the dose of about 8 mg to about 100 mg.

15 . The method of claim 10 , wherein the second therapeutic agent is selected from the group consisting of an alkylating agent, an anthracycline antibiotic, an antimetabolite, an indolequinone, a taxane, and a platinum-based agent.

16 . The method of claim 15 , wherein the second therapeutic agent is selected from the group consisting of mitomycin, epirubicin, doxorubicin, valrubicin, gemcitabine, apaziquone, docetaxel, paclitaxel, and cisplatin.

17 . The method of claim 1 , wherein the limus drug is sirolimus.

18 . The method of claim 1 , wherein the nanoparticles in the composition have an average diameter of no greater than about 200 nm.

19 . The method of claim 1 , wherein the limus drug in the nanoparticles are coated with albumin.

20 . The method of claim 1 , wherein the bladder cancer is urothelial carcinoma.

21 . The method of claim 1 , wherein the bladder cancer is a high grade bladder cancer.

22 . The method of claim 1 , wherein the individual is human.

23 . The method of claim 1 , wherein the individual is selected for treatment based on the level of one of more of: p-S6K, pAKT, p-4EBP1, Ki67, p53, p63, Stathmin, Tau, SPARC, p73, c-myc, and cyclin D1.

24 . The method of claim 23 , further comprising determining the level of one of more of: p-S6K, pAKT, p-4EBP1, Ki67, p53, p63, Stathmin, Tau, SPARC, p73, c-myc, and cyclin D1 prior to treatment.

25 . The method of claim 23 , further comprising selecting the individual for treatment based on a high level of one or more of: p-S6K, pAKT, p-4EBP1, Ki67, p53, p63, Stathmin, Tau, SPARC, p73, c-myc, and cyclin D1.

26 . The method of claim 1 , further comprising determining the level of one of more of: p-S6K, pAKT, p-4EBP1, Ki67, p53, p63, Stathmin, Tau, SPARC, p73, c-myc, and cyclin D1 after the treatment.

Assignees

• Abraxis Bioscience Llc

Inventors

• Desai Neil P

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P13/10

  of the bladder · CPC title