Non-pegylated liposomal doxorubicin triple combination therapy

Abstract

The present invention relates to a method for treating metastatic breast cancer in an individual comprising administering to an individual in need thereof a dosing regimen which comprises administering to the individual nonpegylated liposomal doxorubicin, a taxane and a HER2/neu receptor antagonist, wherein the individual previously has been administered an anthracycline.

1 . A method for treating metastatic breast cancer in an individual comprising administering to an individual in need thereof a dosing regimen which comprises administering to said individual nonpegylated liposomal doxorubicin, a taxane and a HER2/neu receptor antagonist, wherein said individual previously has been administered an anthracycline. 
     
     
         2 . A method according to  claim 1 , wherein said previous administration of anthracycline was for the treatment of cancer. 
     
     
         3 . A method according to  claim 2 , wherein said previous administration of anthracycline was for the treatment of breast cancer. 
     
     
         4 . A method according to  claim 1 , wherein said anthracycline previously administered to said individual is selected from the group consisting of doxorubicin, idarubicin, epirubicin and daunorubicin. 
     
     
         5 . A method according to  claim 4 , wherein said anthracycline previously administered to said individual is doxorubicin. 
     
     
         6 . A method according to  claim 4 , wherein the total amount of said anthracycline previously administered to said individual is from 50 mg/m 2  to 450 mg/m 2 . 
     
     
         7 . A method according to  claim 6 , wherein the total amount of said anthracycline previously administered to said individual is from 100 mg/m 2  to 400 mg/m 2 . 
     
     
         8 . A method according to  claim 1 , wherein said method further comprises administering to said individual a pharmaceutically effective amount of a colony stimulating factor. 
     
     
         9 . A method according to  claim 8 , wherein said colony stimulating factor is a granulocyte colony stimulating factor, a macrophage colony stimulating factor or a granulocyte macrophage colony stimulating factor. 
     
     
         10 . A method according to  claim 8 , wherein said colony stimulating factor is filgrastim, pegfilgrastim, sargramostim, lenograstim or molgramostim. 
     
     
         11 . A method according to  claim 1 , wherein said method further comprises administering to said individual a pharmaceutically effective amount of an antiemetic agent. 
     
     
         12 . A method according to  claim 11 , wherein said antiemetic agent is a 5-HT 3  receptor antagonist, a dopamine antagonist, an NK 1  receptor antagonist, a steroid or a cannabinoid. 
     
     
         13 . A method according to  claim 12 , wherein said antiemetic agent is a 5-HT 3  receptor antagonist. 
     
     
         14 . A method according to  claim 12 , wherein said 5-HT 3  receptor antagonist is dolasetron, granisetron, ondansetron, palonosetron or tropisetron. 
     
     
         15 . A method according to  claim 1 , wherein said previous anthracycline administration comprised adjuvant or neo-adjuvant administration of said anthracycline. 
     
     
         16 . A method according to  claim 15 , wherein said previous anthracycline administration comprised adjuvant administration of said anthracycline. 
     
     
         17 . A method according to  claim 15 , wherein said previous anthracycline administration comprised neo-adjuvant administration of said anthracycline. 
     
     
         18 . A method according to  claim 1 , wherein said dosing regimen does not substantially increase the likelihood that said individual will develop palmar-plantar erythrodysesthesia during or after said dosing regimen. 
     
     
         19 . A method according to  claim 1 , wherein said dosing regimen does not substantially increase the likelihood that said individual will develop cardiotoxicity during or after said dosing regimen. 
     
     
         20 . A method according to  claim 1 , wherein said dosing regimen does not substantially increase the likelihood that said individual will develop a symptom of cardiotoxicity during or after said dosing regimen. 
     
     
         21 . A method according to  claim 20 , wherein said symptom is reduced resting left ventricular ejection fraction. 
     
     
         22 . A method according to  claim 1 , wherein said dosing regimen does not substantially increase the likelihood that said individual will develop congestive heart failure during or after said dosing regimen. 
     
     
         23 . A method according to  claim 22 , wherein said dosing regimen does not substantially increase the likelihood that said individual will develop a symptom of congestive heart failure during or after said dosing regimen. 
     
     
         24 . A method according to  claim 23 , wherein said symptom is dyspnea, tachycardia, cough, neck vein distention, cardiomegaly, hepatomegaly, paroxysmal nocturnal dyspnea, orthopnea or peripheral edema. 
     
     
         25 . A method according to  claim 23 , wherein said symptom is dyspnea, tachycardia, neck vein distention, cardiomegaly, hepatomegaly, paroxysmal nocturnal dyspnea, orthopnea or peripheral edema. 
     
     
         26 . A method according to  claim 1 , wherein said individual is at least 60 years of age. 
     
     
         27 . A method according to  claim 26 , wherein said previous anthracycline administration comprised at least 4 cycles of doxorubicin administration. 
     
     
         28 . A method according to  claim 26 , wherein said individual has a condition that increases the risk of a cardiac-related adverse event resulting from anthracycline administration. 
     
     
         29 . A method according to  claim 28 , wherein said condition is diabetes or hypertension. 
     
     
         30 . A method according to  claim 29 , wherein said condition is diabetes. 
     
     
         31 . A method according to  claim 29 , wherein said condition is hypertension. 
     
     
         32 . A method according to  claim 1 , wherein said individual is at least 65 years of age. 
     
     
         33 . A method according to  claim 32 , wherein said previous anthracycline administration comprised at least 4 cycles of doxorubicin administration. 
     
     
         34 . A method according to  claim 32 , wherein said individual has a condition that increases the risk of a cardiac-related adverse event resulting from anthracycline administration. 
     
     
         35 . A method according to  claim 34 , wherein said condition is diabetes or hypertension. 
     
     
         36 . A method according to  claim 35 , wherein said condition is diabetes. 
     
     
         37 . A method according to  claim 35 , wherein said condition is hypertension. 
     
     
         38 . A method according to  claim 1 , wherein said dosing regimen does not substantially increase the likelihood that said individual will suffer cardiac death during or after said dosing regimen. 
     
     
         39 . A method according to  claim 1 , wherein said HER2/neu receptor antagonist is trastuzumab. 
     
     
         40 . A method according to  claim 39 , wherein said dosing regimen comprises six consecutive 3-week long treatment cycles, and wherein said nonpegylated liposomal doxorubicin is administered on day 1 of each treatment cycle, said taxane is administered on day 1 of each treatment cycle, and said trastuzumab is administered on day 1 of the first treatment cycle and every week thereafter. 
     
     
         41 . A method according to  claim 40 , wherein said nonpegylated liposomal doxorubicin is administered at a dose level of from 30 mg/m 2  to 75 mg/m 2 , said taxane is administered at a dose level of from 50 mg/m 2  to 250 mg/m 2 , and said trastuzumab is administered at a dose level of from 3 mg/kg to 5 mg/kg as a loading dose on day 1 of the first treatment cycle and every week thereafter at a dose level of from 1 mg/kg to 3 mg/kg. 
     
     
         42 . A method according to  claim 41 , wherein said nonpegylated liposomal doxorubicin is administered at a dose level of about 50 mg/m 2  doxorubicin on day 1 of each treatment cycle, said taxane is administered at a dose level of about 80 mg/m 2  on day 1 of the first treatment cycle and every week thereafter or at a dose level of about 75 mg/m 2  on day 1 of each treatment cycle or at a dose level of from 200 mg/m 2  to 250 mg/m 2  on day 1 of each treatment cycle, and said trastuzumab is administered at a dose level of about 4 mg/kg on day 1 of the first treatment cycle and every week thereafter at a dose level of about 2 mg/kg. 
     
     
         43 . A method according to  claim 41 , wherein said taxane is paclitaxel, docetaxel or albumin-bound paclitaxel. 
     
     
         44 . A method according to  claim 43 , wherein said taxane is paclitaxel. 
     
     
         45 . A method according to  claim 44 , wherein said paclitaxel is administered at a dose level of about 80 mg/m 2  on day 1 of the first treatment cycle and every week thereafter. 
     
     
         46 . A method according to  claim 43 , wherein said taxane is docetaxel or albumin-bound paclitaxel. 
     
     
         47 . A method according to  claim 46 , wherein said docetaxel is administered at a dose level of about 75 mg/m 2  on day 1 of each treatment cycle. 
     
     
         48 . A method for treating metastatic breast cancer in an individual comprising administering to an individual in need thereof a dosing regimen which comprises administering to said individual nonpegylated liposomal doxorubicin, trastuzumab and a chemotherapeutic agent selected from the group consisting of capecitabine, vinorelbine, gemcitabine and carboplatin, wherein said individual previously has been administered an anthracycline.