Methods for the In Situ Treatment of Bone Cancer

Abstract

The present invention relates to methods for in situ treatment of malignant cells from a cancer associated with bone. In one method, the treatment is for a primary cancer and entails positioning an implant containing and/or coated with at least one active agent for treating malignant cells directly in/on or indirectly among/near (e.g., by placing the implant in an area immediately proximal to) a site containing the malignant cells. In another method, the treatment includes positioning an implant containing and/or coated with at least one active agent for treating malignant cells directly in/on or indirectly among/near (e.g., by placing the implant in an area immediately proximal to) a surgical site from which malignant cells were previously removed/excised.

1 . A method for in situ treatment of malignant cells from a cancer associated with bone, which comprises positioning among the malignant cells an implant that at least partially chemically and/or physically associates with at least one active agent for treating the malignant cells, wherein the cancer associated with bone is a primary cancer. 
     
     
         2 . The method of  claim 1 , wherein the positioning of the implant occurs such that the implant is directly within a site including the malignant cells. 
     
     
         3 . The method of  claim 1 , wherein the positioning of the implant occurs such that the implant is directly on a site including the malignant cells. 
     
     
         4 . The method of  claim 1 , wherein the positioning of the implant occurs such that the implant is in an area immediately proximal to a site including the malignant cells. 
     
     
         5 . The method of  claim 1 , wherein the implant comprises a screw; a tack; a nail; a pin; a plate; a rod; a clamp; a staple; a spring; a stent; a suture; a membrane; a catheter; a pacemaker or other electronic device lead; or a combination thereof. 
     
     
         6 . The method of  claim 5 , wherein the implant possesses a coating layer comprising a (co)polymer containing repeat units, and/or a (co)polymer made including precursors, of: aliphatic ethers; aliphatic esters; aromatic esters; aliphatic amides; polyamides; siloxanes; urethanes, urethaneureas, or both, having hard segments made from multifunctional isocyanates in combination with multifunctional hydroxy compounds, multifunctional amines, or both; alpha-olefins; at least partially halogenated repeat units; ionomers; hyaluronic acid and/or a salt thereof; collagen; and combinations, copolymers, or reaction products thereof. 
     
     
         7 . The method of  claim 1 , wherein the primary cancer comprises a primary bone cancer. 
     
     
         8 . The method of  claim 1 , wherein the at least one active agent comprises a bisphosphonate, a monophosphonate, vitamin D and/or a vitamin D derivative, calcitonin, a statin, or a combination thereof. 
     
     
         9 . The method of  claim 1 , wherein the at least one active agent comprises an anti-angiogenesis agent, an anticancer agent, an antiproliferative agent, an osteoclast inhibitor, a vasodilator, or a combination thereof. 
     
     
         10 . The method of  claim 1 , wherein the implant comprises a xenograft, heterograft, or allograft portion of bone, soft tissue, extracellular matrix, cartilagenous material, or a combination thereof; a composition of or containing artificial bone, demineralized bone matrix, soft tissue, extracellular matrix, cartilagenous material, or a combination thereof; a bone cement; or a combination thereof. 
     
     
         11 . The method of  claim 10 , wherein the implant possesses a coating layer comprising a (co)polymer containing repeat units, and/or a (co)polymer made including precursors, of: aliphatic ethers; aliphatic esters; aromatic esters; aliphatic amides; polyamides; siloxanes; urethanes, urethaneureas, or both, having hard segments made from multifunctional isocyanates in combination with multifunctional hydroxy compounds, multifunctional amines, or both; alpha-olefins; at least partially halogenated repeat units; ionomers; hyaluronic acid and/or a salt thereof; collagen; and combinations, copolymers, or reaction products thereof. 
     
     
         12 . The method of  claim 1 , wherein the at least one active agent comprises:
 a bisphosphonate selected from the group consisting of etidronate, clodronate, pamidronate, alendronate, olpadronate, amino-olpadronate, ibandronate, neridronate, nedrinate, medronate, tiludronate, risedronate, zolendronate, EA-1053, YM-175, CGP 42′446, YM 529, U-81581, FR-78844, BM-21.0955, and a combination thereof;   vitamin D, a vitamin D derivative, a combination of vitamin D and a vitamin D derivative; and   combinations of any of the preceding agents.   
     
     
         13 . A method for in situ treatment of malignant cells from a cancer associated with bone, which comprises positioning among the malignant cells an implant that at least partially chemically and/or physically associates with at least one active agent for treating the malignant cells, with the proviso that the implant does not comprise a hardened bone cement within the bulk of which the at least one active agent is contained. 
     
     
         14 . The method of  claim 13 , wherein the positioning of the implant occurs such that the implant is directly within a site including the malignant cells. 
     
     
         15 . The method of  claim 13 , wherein the positioning of the implant occurs such that the implant is directly on a site including the malignant cells. 
     
     
         16 . The method of  claim 13 , wherein the positioning of the implant occurs such that the mplant is in an area immediately proximal to a site including the malignant cells. 
     
     
         17 . The method of  claim 13 , wherein the implant comprises a screw; a tack; a nail; a pin; a plate; a rod; a clamp; a staple; a spring; a stent; a suture; a membrane; a catheter; a pacemaker or other electronic device lead; or a combination thereof. 
     
     
         18 . The method of  claim 17 , wherein the implant possesses a coating layer comprising a (co)polymer containing repeat units, and/or a (co)polymer made including precursors, of: aliphatic ethers; aliphatic esters; alkylene esters; aromatic esters ; aliphatic amides; polyamides; siloxanes; urethanes, urethaneureas, or both, having hard segments made from multifunctional isocyanates in combination with multifunctional hydroxy compounds, multifunctional amines, or both; alpha-olefins; at least partially halogenated repeat units; ionomers; hyaluronic acid and/or a salt thereof; collagen; and combinations, copolymers, or reaction products thereof. 
     
     
         19 . The method of  claim 13 , wherein the cancer associated with bone is a primary cancer. 
     
     
         20 . The method of  claim 19 , wherein the primary cancer comprises a primary bone cancer. 
     
     
         21 . The method of  claim 13 , wherein the at least one active agent comprises a bisphosphonate, a monophosphonate, vitamin D and/or a vitamin D derivative, calcitonin, a statin, or a combination thereof. 
     
     
         22 . The method of  claim 13 , wherein the at least one active agent comprises an anti-angiogenesis agent, an anticancer agent, an antiproliferative agent, an osteoclast inhibitor, a vasodilator, or a combination thereof. 
     
     
         23 . The method of  claim 13 , wherein the implant comprises a xenograft, heterograft, or allograft portion of bone, soft tissue, extracellular matrix, cartilagenous material, or a combination thereof; a composition of or containing artificial bone, demineralized bone matrix, soft tissue, extracellular matrix, cartilagenous material, or a combination thereof; a bone cement; or a combination thereof. 
     
     
         24 . The method of  claim 23 , wherein the implant possesses a coating layer comprising a (co)polymer containing repeat units, and/or a (co)polymer made including precursors, of: aliphatic ethers; aliphatic esters; alkylene esters; aromatic esters ; aliphatic amides; polyamides; siloxanes; urethanes, urethaneureas, or both, having hard segments made from multifunctional isocyanates in combination with multifunctional hydroxy compounds, multifunctional amines, or both; alpha-olefins; at least partially halogenated repeat units; ionomers; hyaluronic acid and/or a salt thereof; collagen; and combinations, copolymers, or reaction products thereof. 
     
     
         25 . The method of  claim 13 , wherein the at least one active agent comprises:
 a bisphosphonate selected from the group consisting of etidronate, clodronate, pamidronate, alendronate, olpadronate, amino-olpadronate, ibandronate, neridronate, nedrinate, medronate, tiludronate, risedronate, zolendronate, EB-1053, YM-175, CGP 42′446, YM 529, U-81581, FR-78844, BM-21.0955, and a combination thereof;   vitamin D, a vitamin D derivative, a combination of vitamin D and a vitamin D derivative; and   combinations of any of the preceding agents.   
     
     
         26 . A medical device for in situ treatment of malignant cells from a cancer associated with bone, which comprises:
 a sterile, coated implant selected from the group consisting of a screw; a tack; a nail; a pin; a plate; a rod; a clamp; a staple; a spring; a stent; a suture; a membrane; a catheter; a pacemaker or other electronic device lead; a xenograft, heterograft, or allograft portion of bone, soft tissue, extracellular matrix, cartilagenous material, or a combination thereof; a composition of or containing artificial bone, demineralized bone matrix, soft tissue, extracellular matrix, cartilagenous material, or a combination thereof; a bone cement; or a combination thereof,   wherein the implant possesses a coating layer comprising a (co)polymer that comprises: aliphatic ethers; aliphatic esters; alkylene esters; aromatic esters; aliphatic amides; polyamides; siloxanes; urethanes, urethaneureas, or both, having hard segments made from multifunctional isocyanates in combination with multifunctional hydroxy compounds, multifunctional amines, or both; alpha-olefins; at least partially halogenated repeat units; ionomers; hyaluronic acid and/or a salt thereof; collagen; and combinations, copolymers, or reaction products thereof, and   wherein the implant at least partially chemically and/or physically associates with at least one active agent selected from the group consisting of a bisphosphonate, a monophosphonate, vitamin D and/or a vitamin D derivative, calcitonin, a statin, an anti-angiogenesis agent, an anticancer agent, an antiproliferative agent, an osteoclast inhibitor, a vasodilator, and a combination thereof.   
     
     
         27 . A kit for in situ treatment of malignant cells from a cancer associated with bone, which comprises:
 (1) a sterile, coated implant selected from the group consisting of a screw; a tack; a nail; a pin; a plate; a rod; a clamp; a staple; a spring; a stent; a suture; a membrane; a catheter; a pacemaker or other electronic device lead; a xenograft, heterograft, or allograft portion of bone, soft tissue, extracellular matrix, cartilagenous material, or a combination thereof; a composition of or containing artificial bone, demineralized bone matrix, soft tissue, extracellular matrix, cartilagenous material, or a combination thereof; a bone cement; and a combination thereof,   wherein the implant possesses a coating layer comprising a (co)polymer that comprises: aliphatic ethers; aliphatic esters; alkylene esters; aromatic esters; aliphatic amides; polyamides; siloxanes; urethanes, urethaneureas, or both, having hard segments made from multifunctional isocyanates in combination with multifunctional hydroxy compounds, multifunctional amines, or both; alpha-olefins; at least partially halogenated repeat units; ionomers; hyaluronic acid and/or a salt thereof; collagen; and combinations, copolymers, or reaction products thereof; and   (2) one or more sterile solutions, carriers, or both, each solution, carrier, or combination thereof comprising at least one active agent selected from the group consisting of a bisphosphonate, a monophosphonate, vitamin D and/or a vitamin D derivative, calcitonin, a statin, an anti-angiogenesis agent, an anticancer agent, an antiproliferative agent, an osteoclast inhibitor, a vasodilator, and a combination thereof.