Patent EA-004647-B1 (EA)
Title: Methods of potentiating of intravenous phosphate
Inventor: KOPRESKI MICHAEL S
IPC: A61K9/127
Filed: 1999-03-26
Abstract: 1. A method of administering estramustine phosphate as an intravenous dose, whereby the dosage of a single infusion exceeds 950 mg/m<2>. 2. The method of claims 1, wherein estramustine phosphate is administered as a single infusion on a once weekly schedule. 3. The method of claims 1, wherein estramustine phosphate is administered as a single infusion on a once every two week schedule. 4. The method of claims 1, wherein estramustine phosphate is administered as a single infusion on a once every three week schedule. 5. The method of claims 1, wherein estramustine phosphate is administered as a single infusion on a once every four week schedule. 6. The method of claims 1, wherein the infusion is given over 30 minutes to 3 hours. 7. The method of claims 1, wherein relief from cancer-induced urinary obstruction is achieved. 8. The method of claim 1, wherein rapid relief of cancer-induced pain is achieved. 9. The method of claim 1, in which estramustine phosphate is administered in combination with other anti-cancer therapies. 10. The method of claim 6, wherein estramustine phosphate is administered intravenously in combination with other chemotherapeutic agents. 11. A method of potentiating the therapeutic benefit of a multi-drug chemotherapeutic regimen, wherein one of the drugs in the regimen comprises estramustine, by administering estramustine phosphate as an intravenous formulation. 12. The method of claim 11, wherein said intravenous formulation comprises estramustine phosphate given at high dose. 13. The method of claim 11, wherein another drug in the regimen comprises an anti-mitotic agent or anti-microtubule agent. 14. The method of claim 11, wherein mother drug in said regimen is CPT-11. 15. The method of claim 11, wherein another drug in said regimen is doxorubicin. 16. The method of claim 11, wherein another drug in said regimen is etoposide. 17. The method of claim 11, wherein another drug in said regimen is navelbine. 18. The method of claim 11, wherein another drug in said regimen is vinblastine. 19. The method of claim 12, wherein the dosage of a single infusion of estramustine phosphate exceeds 950 mg/m<2>. 20. The method of claim 13, wherein said anti-microtubule agent is a taxane. 21. The method of claim 13, wherein said anti-microtubule agent is a taxane. 22. A method to produce prolonged elevated plasma levels of estramustine to promote synergistic interaction between estramustine and a second chemotherapeutic agent, wherein: estramustine is administered as an intravenous formulation; and estramustine is administered on the day of, or within 3 days of administration of said second chemotherapeutic agent. 23. The method of claim 22, wherein said second chemotherapeutic agent comprises an anti-mitotic agent or anti-microtubule agent. 24. The method of claim 22, wherein the intravenous formulation comprises estramustine phosphate. 25. The method of claim 23, wherein said anti-microtubule agent is a taxane. 26. The method of claim 24, wherein the dosage of a single infusion of estramustine phosphate exceeds 950 mg/m<2>. 27. A method to produce elevated plasma levels of the estramustine metabolite estromustine, to promote synergistic interaction between estromustine and a second chemotherapeutic agent, wherein: estrastine is administered as an intravenous formulation; and estramustine is administered on the day of, or within 3 days of administration of said second therapeutic agent. 28. The method of claim 27, wherein said second therapeutic agent comprises an anti-mitotic agent or anti-microtubule agent. 29. The method of claim 27, wherein the intravenous formulation comprises estramustine phosphate. 30. The method of claim 28, wherein said anti-microtubule agent is a taxane. 31. The method of claim 29, wherein the dosage of a single infusion of estramustine phosphate exceeds 950 mg/m<2>. 32. A method to sustain plasma levels of estramustine and estromustine, wherein estramustine phosphate is administered intravenously as a single infusion at a dosage exceeding 950 mg/m<2>, optionally repeating the infusion in a serial manner. 33. A method of increasing binding saturation of estramustine or its metabolites to estramustine binding protein or like-protein wherein estramustine is administered as an intravenous formulation as estramustine phosphate at a single infusion dosage exceeding 950 mg/m<2>. 34. A method of prolonging binding duration of estramustine or its metabolites to estramustine binding protein, or like-protein wherein: estramustine is administered as an intravenous formulation as estramustine phosphate at a single infusion dosage exceeding 950 mg/m<2>. 35. A method for the treatment of prostate cancer, having estramustine binding protein or like-protein, comprising the administering of intravenous formulation as estramustine phosphate at a single infusion dosage exceeding 950 mg/m<2>. 36. The method of claim 27, wherein estramustine phosphate is administered intravenously in combination with other chemotherapeutic agents. 37. The method of claim 31, wherein said liposome encapsulated taxane is liposome encapsulated paclitaxel. 38. A method of potentiating the therapeutic benefit of a multi-drug chemotherapeutic regimen wherein one drug in the regimen comprises a taxane, and wherein another drug in the regimen comprises estramustine phosphate, and wherein estramustine phosphate is administered intravenously at a dosage exceeding 950 mg/m<2>. 39. A method of administering estramustine phosphate, wherein estramustine phosphate is first encapsulated within liposomes, and then administered intravenously. 40. A formulation of estramustine phosphate, wherein estramustine is encapsulated within liposomes. 41. A method of treating cancer wherein liposome-encapsulated estramustine phosphate is administered. 42. A chemotherapeutic agent consisting of estramustine phosphate encapsulated within liposome. 43. A formulation according to claim 41 intended for intravenous administration. 44. A product, comprising estramustine phosphate suitable for intravenous administration and one or more chemotherapeutic agents, as a combined preparation for simultaneous, separate or sequential use in anticancer therapy. 45. A product according to claim 44, wherein said one or more chemotherapeutic agents are selected from the group consisting of CPT-11, doxorubicin, etoposide, navelbine and a taxane derivative. 46. A product according to claim 44, wherein said estramustine phosphate suitable for intravenous administration is used as a single dosage infusion exceeding 950 mg/m<2>. 47. A product according to anyone of claims 44 to 46 for the treatment of prostate cancer. 48. A method for the treatment of prostate cancer, comprising the administration of a product according to anyone of claims 44-47. 49. A formulation intended for intravenous administration, comprising estramustine phosphate in mixture with albumin. 50. Formulation of claim 49, wherein a single infusion dosage of an active ingredient exceeds 950 mg/m<2>. 51. Formulation of claim 49 or 50, wherein albumin is human albumin. 52. A product, comprising (i) formulation according to claim 49 and (ii) one or more chemotherapeutic agents, as a combined preparation for simultaneous, separate or sequential use in anticancer therapy. 53. A product according to claim 52, wherein said one or more chemotherapeutic agents are selected from the group consisting of CPT-11, doxorubicin, etoposide, navelbine and a taxane derivative. 54. A product, comprising estramustine phosphate, in frozen-dried form, and physiological solution for parenteral use, containing albumin.