Treatment with anti-vegf antibodies

Abstract

This invention concerns in general treatment of diseases and pathological conditions with anti-VEGF antibodies. More specifically, the invention concerns the treatment of human patients susceptible to or diagnosed with cancer using an anti-VEGF antibody, preferably in combination with one or more additional anti-tumor therapeutic agents.

What is claimed is: 
     
         1 . A method of treating cancer in a human patient, comprising administering to the patient effective amounts of an anti-VEGF antibody and an anti-neoplastic composition, wherein said anti-neoplastic composition comprises at least one chemotherapeutic agent. 
     
     
         2 . The method of  claim 1 , wherein the cancer is selected from the group consisting of breast cancer, colorectal cancer, rectal cancer, non-small cell lung cancer, non-Hodgkins lymphoma (NHL), renal cell cancer, prostate cancer, liver cancer, pancreatic cancer, soft-tissue sarcoma, kaposi's sarcoma, carcinoid carcinoma, head and neck cancer, melanoma, ovarian cancer, mesothelioma, and multiple myeloma. 
     
     
         3 . The method of  claim 1 , wherein the cancer is metastatic. 
     
     
         4 . The method of  claim 1 , wherein the patient is previously untreated. 
     
     
         5 . The method of  claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of alkylating agents, antimetabolites, folic acid analogs, pyrimidine analogs, purine analogs and related inhibitors, vinca alkaloids, epipodophyllotoxins, antibiotics, L-Asparaginase, topoisomerase inhibitor, interferons, platinum coordination complexes, anthracenedione substituted urea, methyl hydrazine derivatives, adrenocortical suppressant, adrenocorticosteroides, progestins, estrogens, antiestrogen, androgens, antiandrogen, and gonadotropin-releasing hormone analog. 
     
     
         6 . The method of  claim 5 , wherein the chemotherapeutic agent is selected from the group consisting of 5-fluorouracil (5-FU), leucovorin, irinotecan, oxaliplatin, capecitabine, paclitaxel and doxetaxel. 
     
     
         7 . The method of  claim 1 , wherein the anti-neoplastic composition comprises a combination of at least two chemotherapeutic agents. 
     
     
         8 . The method of  claim 7 , wherein the anti-neoplastic composition comprises 5-FU and leucovorin. 
     
     
         9 . The method of  claim 7 , wherein the anti-neoplastic composition comprises 5-FU, leucovorin and irinotecan. 
     
     
         10 . The method of  claim 1 , wherein upon completing treatment with the anti-VEGF antibody and the anti-neoplastic composition, the patient receives further chemotherapeutic treatment with at least one chemotherapeutic agent. 
     
     
         11 . The method of  claim 10 , wherein the chemotherapeutic agent used in further chemotherapeutic treatment is selected from the group consisting of 5-FU, leucovorin, irinotecan, oxaliplatin, capecitabine, paclitaxel and doxetaxel. 
     
     
         12 . The method of  claim 11 , wherein the chemotherapeutic agent is oxaliplatin. 
     
     
         13 . The method of  claim 1 , wherein said anti-VEGF antibody binds the same epitope as the monoclonal anti-VEGF antibody A4.6.1 produced by hybridoma ATCC HB 10709. 
     
     
         14 . The method of  claim 1 , wherein the anti-VEGF antibody is a human antibody. 
     
     
         15 . The method of  claim 1 , wherein the anti-VEGF antibody is a humanized antibody. 
     
     
         16 . The method of  claim 15 , wherein the anti-VEGF antibody is a humanized A4.6.1 antibody or fragment thereof. 
     
     
         17 . The method of  claim 1 , wherein the anti-VEGF antibody is administered intravenously. 
     
     
         18 . The method of  claim 1 , wherein the anti-VEGF antibody is administered to the patient at about 5 mg/kg every 2 to 3 weeks. 
     
     
         19 . The method of  claim 1 , whereby the co-administration of the anti-VEGF antibody and the anti-neoplastic composition effectively increases the duration of survival of the human patient. 
     
     
         20 . The method of  claim 19 , wherein the duration of survival of the patient is increased by at least about 2 months when compared to another patient treated with the anti-neoplastic composition alone. 
     
     
         21 . The method of  claim 1 , whereby the co-administration of the anti-VEGF antibody and the anti-neoplastic composition effectively increases the duration of progression free survival of the human patient. 
     
     
         22 . The method of  claim 21 , wherein the progression free survival of the patient is increased by at least about 2 months when compared to another patient treated with the anti-neoplastic composition alone. 
     
     
         23 . The method of  claim 1 , whereby the co-administration of the anti-VEGF antibody and the anti-neoplastic composition effectively increases the response rate in a group of human patients. 
     
     
         24 . The method of  claim 23 , wherein the response rate of the group of human patients is significantly increased with a Chi-square p-value of less than 0.005 when compared to another group of patients treated with the anti-neoplastic composition alone. 
     
     
         25 . The method of  claim 1 , whereby the co-administration of the anti-VEGF antibody and the anti-neoplastic composition effectively increases the duration of response of the human patient. 
     
     
         26 . The method of  claim 25 , wherein the duration of response of the patient is increased by at least about 2 months when compared to another patient treated with the anti-neoplastic composition alone. 
     
     
         27 . A method of treating a human patient susceptible to or diagnosed with colorectal cancer, comprising administering to the patient effective amounts of an anti-VEGF antibody. 
     
     
         28 . The method of  claim 27 , wherein the colorectal cancer is metastatic. 
     
     
         29 . The method of  claim 27 , wherein said anti-VEGF antibody binds the same epitope as the monoclonal anti-VEGF antibody A4.6.1 produced by hybridoma ATCC HB 10709. 
     
     
         30 . The method of  claim 27 , wherein the anti-VEGF antibody is a human antibody. 
     
     
         31 . The method of  claim 27 , wherein the anti-VEGF antibody is a humanized antibody. 
     
     
         32 . The method of  claim 31 , wherein the anti-VEGF antibody is a humanized A4.6.1 antibody or fragment thereof. 
     
     
         33 . The method of  claim 27 , wherein the anti-VEGF antibody is administered by intravenous infusion. 
     
     
         34 . The method of  claim 27 , wherein the anti-VEGF antibody is administered to the patient at about 5 mg/kg every 2 to 3 weeks. 
     
     
         35 . The method of  claim 27 , further comprising administering to the patient one or more chemotherapeutic agents. 
     
     
         36 . The method of  claim 35 , wherein the chemotherapeutic agent is selected from the group consisting of alkylating agents, antimetabolites, folic acid analogs, pyrimidine analogs, purine analogs and related inhibitors, vinca alkaloids, epipodophyllotoxins, antibiotics, L-Asparaginase, topoisomerase inhibitor, interferons, platinum coordination complexes, anthracenedione substituted urea, methyl hydrazine derivatives, adrenocortical suppressant, adrenocorticosteroides, progestins, estrogens, antiestrogen, androgens, antiandrogen, and gonadotropin-releasing hormone analog. 
     
     
         37 . The method of  claim 35 , wherein the chemotherapeutic agent is selected from the group consisting of 5-fluorouracil, leucovorin, irinotecan, oxaliplatin, capecitabine, paclitaxel and doxetaxel. 
     
     
         38 . A method of treating a human patient or a group of human patients having metastatic colorectal cancer, comprising administering to the patient effective amounts of an anti-VEGF antibody composition and an anti-neoplastic composition, wherein said anti-neoplastic composition comprises a fluorouracil based combination of chemotherapeutic agents, whereby the co-administration of the anti-VEGF antibody and the anti-neoplastic composition results in statistically significant and clinically meaningful improvement of the treated patient as measured by the duration of survival, progression free survival, response rate or duration of response. 
     
     
         39 . The method of  claim 38 , wherein the anti-neoplastic composition comprises 5-FU, leucovorin and irinotecan. 
     
     
         40 . The method of  claim 39 , wherein the anti-neoplastic composition comprises the regimen having 500 mg/m 2  5-FU, 20 mg/m 2  leucovorin and 125 mg/m 2  irinotecan and is administered to the patient in repeating 6-week cycles consisting of weekly administrations for 4 weeks followed by 2 weeks of rest, and wherein the anti-VEGF antibody is administered to the patient at 5 mg/kg every other week. 
     
     
         41 . The method of  claim 38 , wherein the anti-neoplastic composition comprises 5-FU and leucovorin. 
     
     
         42 . The method of  claim 41 , wherein the 5-FU and leucovorin are administered to the patient at 500 mg/m 2  each in repeating 8 week cycles consisting of weekly administrations for 4 weeks followed by 2 weeks of rest, and wherein the anti-VEGF antibody is administered to the patient at 5 mg/kg every other week. 
     
     
         43 . The method of  claim 41  for human patients considered non-optimal candidates for first-line irinotecan therapy. 
     
     
         44 . The method of  claim 38 , wherein the anti-neoplastic composition comprises 5-FU, leucovorin and oxaliplatin. 
     
     
         45 . An article of manufacture comprising a container, a composition within the container comprising an anti-VEGF antibody and a package insert instructing the user of the composition to administer to a cancer patient the anti-VEGF antibody composition and an anti-neoplastic composition comprising at least one chemotherapeutic agent. 
     
     
         46 . A kit for treating cancer in a human patient comprising a package comprising an anti-VEGF antibody composition and instructions for using the anti-VEGF antibody composition and an anti-neoplastic composition comprising at least one chemotherapeutic agent for treating cancer in a patient.