Treatment with anti-ErbB2 antibodies

Abstract

The present invention concerns the treatment of disorders characterized by the overexpression of ErbB2. More specifically, the invention concerns the treatment of human patients susceptible to or diagnosed with cancer overexpressing ErbB2 with a combination of an anti-ErbB2 antibody and a chemotherapeutic agent other than an anthracycline, e.g. doxorubicin or epirubicin. The invention further provides a method of treating cancer in a human patient comprising administering effective amounts of an anti-ErbB2 antibody and a cardioprotectant to the patient.

What is claimed is:  
     
         1 . A method for the treatment of a human patient susceptible to or diagnosed with a disorder characterized by overexpression of ErbB2 receptor, comprising administering an effective amount of a combination of an anti-ErbB2 antibody and a chemotherapeutic agent other than an anthracycline derivative, in the absence of an anthracycline derivative, to the human patient.  
     
     
         2 . The method of  claim 1  wherein said disorder is a benign or malignant tumor.  
     
     
         3 . The method of  claim 1  wherein said disorder is a cancer.  
     
     
         4 . The method of  claim 3  wherein said cancer is selected from the group consisting of breast cancer, leukemia, squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, colon cancer, colorectal cancer, endometrial carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer.  
     
     
         5 . The method of  claim 4  wherein said cancer is breast cancer.  
     
     
         6 . The method of  claim 5  wherein said cancer is metastatic breast carcinoma.  
     
     
         7 . The method of  claim 1  wherein said antibody binds to the extracellular domain of the ErbB2 receptor.  
     
     
         8 . The method of  claim 7  wherein said antibody binds to epitope 4D5 within the ErbB2 extracellular domain sequence.  
     
     
         9 . The method of  claim 8  wherein said antibody is a humanized 4D5 anti-ErbB2 antibody.  
     
     
         10 . The method of  claim 1  wherein said chemotherapeutic agent is a taxoid.  
     
     
         11 . The method of  claim 10  wherein said taxoid is paclitaxel or docetaxel.  
     
     
         12 . The method of  claim 1  wherein the effective amount of said combination is lower than the sum of the effective amounts of said anti-ErbB2 antibody and said chemotherapeutic agent, when administered individually, as single agents.  
     
     
         13 . The method of  claim 1  wherein efficacy is measured by determining the time to disease progression or the response rate.  
     
     
         14 . A method for the treatment of a human patient diagnosed with a disorder characterized by overexpression of ErbB2 receptor, comprising administering an effective amount of a combination of an anti-ErbB2 antibody and a chemotherapeutic agent selected from the group consisting of alkylating agents such as thiotepa and cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide and trimethylolomelamine; nitrogen mustards such as chlorambucil, chlomaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, ranimustine; antibiotics such as aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, calicheamicin, carabicin, carzinophilin, chromomycins, dactinomycin, daunorubicin, 6-diazo-5-oxo-L-norleucine, mitomycins, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine, 5-FU; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfomithine; elliptinium acetate; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidamine; mitoguazone; mitoxantrone; mopidamol; nitracrine; pentostatin; phenamet; pirarubicin; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK®; razoxane; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2, 2′,2″-trichlorotriethylamine; urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids such as paclitaxel and docetaxel; chlorambucil; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitomycin C; mitoxantrone; vincristine; vinorelbine; navelbine; novantrone; teniposide; daunomycin; carminomycin; aminopterin; xeloda; ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluoromethylomithine (DMFO); retinoic acid; esperamicins; capecitabine; hormonal agents that act to regulate or inhibit hormone action on tumors such as anti-estrogens including for example tamoxifen, raloxifene, aromatase inhibiting 4(5)-imidazoles, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone; and anti-androgens such as flutamide and nilutamide; and pharmaceutically acceptable salts, acids or derivatives of any of the above, in the absence of an anthracycline derivative, to the human patient.  
     
     
         15 . A method for the treatment of a human patient with a malignant tumor or cancer that expresses ErbB2 receptor, comprising administering to the patient a combination of an antibody that binds ErbB2 and an aromatase inhibitor in an amount effective to extend the time to disease progression in the patient.  
     
     
         16 . The method of  claim 15  wherein the patient has a cancer selected from the group consisting of breast cancer, squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, colon cancer, colorectal cancer, endometrial carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, head cancer and neck cancer.  
     
     
         17 . The method of  claim 15  wherein the malignant tumor or cancer is breast cancer.  
     
     
         18 . The method of  claim 15  wherein the antibody is a humanized 4D5 anti-ErbB2 antibody.  
     
     
         19 . A method for the treatment of a human patient with metastatic breast cancer, comprising administering to the patient a combination of an antibody that binds ErbB2 and an aromatase inhibitor in an amount effective to extend the time to disease progression in the patient.