Chemoprotective methods and compositions

US 8,026,227 B2
Filed: 12/13/2006
Issued: 09/27/2011
Est. Priority Date: 12/13/2005
Status: Expired due to Fees

First Claim

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1. A method of reducing, alleviating, mitigating, or delaying toxicity in a subject receiving a chemotherapeutic agent, comprising administering to the subject in need thereof a pharmaceutically-effective amount of 2,2′

-dithio-bis-ethane sulfonate at a rate of about 0.1 g/min. to about 2.0 g/min.

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Abstract

Compositions and methods for reducing, preventing, mitigating, and/or delaying the onset of, attenuating the severity of, and/or hastening the resolution of, for example, one or more chemotherapy-associated toxicities in a subject receiving one or more chemotherapeutic agents.

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159 Claims

1. A method of reducing, alleviating, mitigating, or delaying toxicity in a subject receiving a chemotherapeutic agent, comprising administering to the subject in need thereof a pharmaceutically-effective amount of 2,2′
- -dithio-bis-ethane sulfonate at a rate of about 0.1 g/min. to about 2.0 g/min.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40)
- - 2. A method of claim 1 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a rate of about 0.2 g/min. to about 1.0 g/min.
  - 3. A method of claim 1 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a rate of about 0.7 g/min.
  - 4. A method of any one of claim 1, 2 or 3 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered over a period of about 45 minutes.
  - 5. A method of any one of claim 1, 2 or 3 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a concentration of about 100 mg/mL.
  - 6. A method of any one of claim 1, 2 or 3 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered over a period of about 45 minutes, at a concentration of about 100 mg/mL.
  - 7. A method of any one of claim 1, 2 or 3 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is a pharmaceutically-acceptable salt.
  - 8. A method of claim 7 wherein said salt is a disodium salt.
  - 9. A method of claim 7, wherein said salt is selected from the group consisting of:
    - a monosodium salt, a sodium potassium salt, a dipotassium salt, a calcium salt, a magnesium salt, a manganese salt, an ammonium salt, or a monopotassium salt.
  - 10. A method of any one of claim 1, 2 or 3 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every five weeks.
  - 11. A method of claim 1 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every three weeks.
  - 12. A method of claim 1 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every two weeks.
  - 13. A method of claim 1 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every week.
  - 14. A method of claim 1 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered in a time period which is selected from the group consisting of;
      
      about once every day, about once every two days, about once every three days, about once every four days, once about every five days, or about once every six days.
  - 15. A method of claim 1 wherein the method reduces, alleviates, mitigates, or delays more than one form of toxicity associated with administration of the chemotherapeutic agent.
  - 16. A method of claim 1 wherein said toxicity is neurotoxicity.
  - 17. A method of claim 1 wherein said toxicity is nephrotoxicity.
  - 18. A method of claim 1 wherein said toxicity is myelosuppression.
  - 19. A method of claim 1 wherein said toxicity is hepatotoxicity.
  - 20. A method of claim 1 wherein said toxicity is nausea and emesis.
  - 21. A method of claim 1 wherein the method allows shorter duration between chemotherapeutic agent treatment cycles.
  - 22. A method of claim 1 wherein the method allows an increase in the dosage of the chemotherapeutic agent.
  - 23. A method of claim 1 wherein the method allows an increase in the number of chemotherapeutic treatments.
  - 24. A method of claim 1 further comprising administering a pre-therapy treatment at least one day prior to chemotherapy, prior to each chemotherapeutic treatment, immediately prior to each chemotherapeutic treatment, concomitantly with or simultaneously during chemotherapeutic treatment, immediately subsequent to chemotherapy, or subsequent to chemotherapy.
  - 25. A method of claim 1 wherein the chemotherapeutic agent is a taxane analog.
  - 26. A method of claim 1 wherein the chemotherapeutic agent is docetaxel.
  - 27. A method of claim 1 wherein the chemotherapeutic agent is paclitaxel.
  - 28. A method of claim 1 wherein the chemotherapeutic agent is a platinum analog.
  - 29. A method of claim 1 wherein the chemotherapeutic agent is cisplatin.
  - 30. A method of claim 1 wherein the chemotherapeutic agent is carboplatin.
  - 31. A method of claim 1 wherein the chemotherapeutic agent is oxaliplatin.
  - 32. A method of claim 1 wherein the chemotherapeutic agent is satraplatin.
  - 33. A method of claim 1 further comprising the administration of one or more chemotherapeutic agents.
  - 34. A method of claim 33, wherein said chemotherapeutic agents are selected from a group consisting of:
    - platinum analogs, and/or, taxanes and taxane analogs.
  - 35. A method of claim 1 further comprising one or more hydration steps.
  - 36. A method of claim 33 wherein the chemotherapeutic agent or agents is utilized for the treatment of a subject with lung cancer or adenocarcinoma.
  - 37. A method of claim 36 wherein the subject is human.
  - 38. A method of claim 1 wherein the 2,2′
    - -dithio-bis-ethane sulfonate is in a form suitable for oral administration.
  - 39. A method of claim 1 wherein the 2,2′
    - -dithio-bis-ethane sulfonate is in a form suitable for parenteral administration.
  - 40. A method of claim 39 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered intravenously.

41. A method of reducing, alleviating, mitigating, or delaying toxicity in a subject receiving a chemotherapeutic agent, comprising administering to said subject in need thereof a pharmaceutically-effective amount of 2,2′
- -dithio-bis-ethane sulfonate at a rate of about 1 mg/mL/min. to about 50 mg/mL/min.
- View Dependent Claims (42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81)
- - 42. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a rate of about 1 mg/mL/min. to about 20 mg/mL/min.
  - 43. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a rate of about 7 mg/mL/min.
  - 44. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered over a period of about 45 minutes.
  - 45. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a concentration of about 100 mg/mL.
  - 46. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered over a period of about 45 minutes, at a concentration of about 100 mg/mL.
  - 47. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is a pharmaceutically-acceptable salt.
  - 48. A method of claim 47 wherein said salt is a disodium salt.
  - 49. A method of claim 47 wherein said salt is selected from the group consisting of:
    - a monosodium salt, a sodium potassium salt, a dipotassium salt, a calcium salt, a magnesium salt, a manganese salt, an ammonium salt, or a monopotassium salt.
  - 50. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every five weeks.
  - 51. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every three weeks.
  - 52. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every two weeks.
  - 53. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every week.
  - 54. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered in a time period which is selected from the group consisting of;
      
      about once every day, about once every two days, about once every three days, about once every four days, once about every five days, or about once every six days.
  - 55. A method of claim 41 wherein said method reduces, alleviates, mitigates, or delays more than one form of toxicity associated with administration of the chemotherapeutic agent.
  - 56. The method of claim 41 wherein said toxicity is neurotoxicity.
  - 57. A method of claim 41 wherein said toxicity is nephrotoxicity.
  - 58. A method of claim 41 wherein said toxicity is myelosuppression.
  - 59. A method of claim 41 wherein said toxicity is hepatotoxicity.
  - 60. A method of claim 41 wherein said toxicity is nausea and emesis.
  - 61. A method of claim 41 wherein said method allows shorter duration between chemotherapeutic agent treatment cycles.
  - 62. A method of claim 41 wherein said method allows an increase in the dosage of the chemotherapeutic agent.
  - 63. A method of claim 41 wherein said method allows an increase in the number of chemotherapeutic treatments.
  - 64. A method of claim 41 further comprising administering a pre-therapy treatment at least one day prior to chemotherapy, prior to each chemotherapeutic treatment, immediately prior to each chemotherapeutic treatment, concomitantly with or simultaneously during chemotherapy treatment, immediately subsequent to chemotherapy, or subsequent to chemotherapy.
  - 65. A method of claim 41 wherein said chemotherapeutic agent is a taxane analog.
  - 66. A method of claim 41 wherein said chemotherapeutic agent is docetaxel.
  - 67. A method of claim 41 wherein said chemotherapeutic agent is paclitaxel.
  - 68. A method of claim 41 wherein said chemotherapeutic agent is a platinum analog.
  - 69. A method of claim 41 wherein said chemotherapeutic agent is cisplatin.
  - 70. A method of claim 41 wherein said chemotherapeutic agent is carboplatin.
  - 71. A method of claim 41 wherein said chemotherapeutic agent is oxaliplatin.
  - 72. A method of claim 41 wherein the chemotherapeutic agent is satraplatin.
  - 73. A method of claim 41 further comprising the administration of one or more chemotherapeutic agents.
  - 74. A method of claim 73, wherein said chemotherapeutic agents are selected from a group consisting of:
    - platinum analogs, and/or, taxanes and taxane analogs.
  - 75. A method of claim 41 additionally comprising one or more hydration steps.
  - 76. A method of claim 73 wherein said chemotherapeutic agent or agents is utilized for the treatment of a subject with lung cancer and adenocarcinoma.
  - 77. A method of claim 76 wherein said subject is human.
  - 78. A method of claim 76 wherein the chemotherapeutic agent is for treating any one or more cancers selected from the group consisting of:
    - ovary, breast, lung, esophagus, stomach, pancreas, liver (including bile ducts, gall bladder and Ampulla of Vater), testes, germ cell, bone, cartilage, head, neck, oral mucosa, colorectal area, anus, kidney, bladder, uroepithelium, prostate, endometrium, uterus, cervix, fallopian tube, central nervous system, peripheral nervous system, and other cancers such as lymphoma, melanoma, mesothelioma, myeloma, leukemia, and Kaposi'"'"'s sarcoma.
  - 79. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is in a form suitable for oral administration.
  - 80. A method of claim 41 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is in a form suitable for parenteral administration.
  - 81. A method of claim 80 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered intravenously.

82. A method of reducing, alleviating, mitigating or delaying toxicity in a subject receiving a chemotherapeutic agent, comprising administering to said subject in need thereof a composition comprising a pharmaceutically-effective amount of 2,2′
- -dithio-bis-ethane sulfonate, wherein said composition has an osmolarity of about 0.1- to about 5-times the osmolarity of the normal plasma of said subject.
- View Dependent Claims (83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119)
- - 83. A method of claim 82 wherein said composition has an osmolarity of about 2- to about 4-times the osmolarity of the normal plasma of said subject.
  - 84. A method of claim 82 wherein said composition has an osmolarity of about 3-times the osmolarity of the osmolarity of the normal plasma of said subject.
  - 85. A method of claim 82 wherein said composition is administered from about once a day to about once every five weeks.
  - 86. A method of claim 82 wherein said composition is administered from about once a day to about once every three weeks.
  - 87. A method of claim 82 wherein said composition is administered from about once a day to about once every two weeks.
  - 88. A method of claim 82 wherein said composition is administered from about once a day to about once every week.
  - 89. A method of claim 82 wherein said composition is administered in a time period which is selected from the group consisting of:
    - about once every day, about once every two days, about once every three days, about once every four days, once about every five days, or about once every six days.
  - 90. A method of claim 82 wherein said method reduces, prevents alleviates, mitigates, or delays more than one form of toxicity associated with administration of the chemotherapeutic agent.
  - 91. A method of claim 82 wherein said toxicity is neurotoxicity.
  - 92. A method of claim 82 wherein said toxicity is nephrotoxicity.
  - 93. A method of claim 82 wherein said toxicity is myelosuppression.
  - 94. A method of claim 82 wherein said toxicity is hepatotoxicity.
  - 95. A method of claim 82 wherein said toxicity is nausea and emesis.
  - 96. A method of claim 82 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is a pharmaceutically-acceptable salt.
  - 97. A method of claim 96 wherein said salt is a disodium salt.
  - 98. A method of claim 96, wherein said salt is selected from the group consisting of:
    - a monosodium salt, a sodium potassium salt, a dipotassium salt, a calcium salt, a magnesium salt, a manganese salt, an ammonium salt, or a monopotassium salt.
  - 99. A method of claim 82 wherein said method allows shorter duration between chemotherapeutic agent treatment cycles.
  - 100. A method of claim 82 wherein said method allows an increase in the dosage of the chemotherapeutic agent.
  - 101. A method of claim 82 wherein said method allows an increase in the number of chemotherapeutic treatments.
  - 102. A method of claim 82 further comprising administering a pre-therapy treatment at least one day prior to chemotherapy, prior to each chemotherapeutic treatment, immediately prior to each chemotherapeutic treatment, concomitantly with or simultaneously during chemotherapy treatment, immediately subsequent to chemotherapy, or subsequent to chemotherapy.
  - 103. A method of claim 82 wherein said chemotherapeutic agent is a taxane analog.
  - 104. A method of claim 82 wherein said chemotherapeutic agent is docetaxel.
  - 105. A method of claim 82 wherein said chemotherapeutic agent is paclitaxel.
  - 106. A method of claim 82 wherein said chemotherapeutic agent is a platinum analog.
  - 107. A method of claim 82 wherein said chemotherapeutic agent is cisplatin.
  - 108. A method of claim 82 wherein said chemotherapeutic agent is carboplatin.
  - 109. A method of claim 82 wherein said chemotherapeutic agent is oxaliplatin.
  - 110. A method of claim 82 wherein the chemotherapeutic agent is satraplatin.
  - 111. A method of claim 82 further comprising the administration of one or more chemotherapeutic agents.
  - 112. A method of claim 111, wherein said chemotherapeutic agents are selected from a group consisting of:
    - platinum analogs, and/or, taxanes and taxane analogs.
  - 113. A method of claim 82 further comprising one or more hydration steps.
  - 114. A method of claim 111 wherein said chemotherapeutic agent or agents is utilized for the treatment of a subject with lung cancer and adenocarcinoma.
  - 115. A method of claim 114 wherein said subject is human.
  - 116. A method of claim 114 wherein the chemotherapeutic agent is for treating any one or more cancers selected from the group consisting of:
    - ovary, breast, lung, esophagus, stomach, pancreas, liver (including bile ducts, gall bladder and Ampulla of Vater), testes, germ cell, bone, cartilage, head, neck, oral mucosa, colorectal area, anus, kidney, bladder, uroepithelium, prostate, endometrium, uterus, cervix, fallopian tube, central nervous system, peripheral nervous system, and other cancers such as lymphoma, melanoma, mesothelioma, myeloma, leukemia, and Kaposi'"'"'s sarcoma.
  - 117. A method of claim 82 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is in a form suitable for oral administration.
  - 118. A method of claim 82 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is in a form suitable for parenteral administration.
  - 119. A method of claim 118 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered intravenously.

120. A method of reducing, alleviating, mitigating, or delaying toxicity in a subject receiving a chemotherapeutic agent, comprising administering to said subject in need thereof a pharmaceutically-effective amount of a 2,2′
- -dithio-bis-ethane sulfonate at a rate of about 0.1 g/min to about 4.6 g/min, at a total dose of about 4 g/m²to about 35 g/m².
- View Dependent Claims (121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159)
- - 121. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a rate of about 0.2 g/min. to about 2.0 g/min.
  - 122. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a rate of about 0.7 g/min.
  - 123. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered over a period of about 45 minutes.
  - 124. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered at a concentration of about 100 mg/mL.
  - 125. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered over a period of about 45 minutes, at a concentration of about 100 mg/mL.
  - 126. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is comprised of a pharmaceutically-acceptable salt.
  - 127. A method of claim 126 wherein said salt is a disodium salt.
  - 128. A method of claim 126 wherein said salt is selected from the group consisting of:
    - a monosodium salt, a sodium potassium salt, a dipotassium salt, a calcium salt, a magnesium salt, a manganese salt, an ammonium salt, or a monopotassium salt.
  - 129. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every five weeks.
  - 130. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every three weeks.
  - 131. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every two weeks.
  - 132. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered from about once a day to about once every week.
  - 133. A method of claim 120 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered in a time period which is selected from the group consisting of;
      
      about once every day, about once every two days, about once every three days, about once every four days, once about every five days, or about once every six days.
  - 134. A method of claim 120 wherein the method reduces, alleviates, mitigates, or delays more than one form of toxicity associated with administration of the chemotherapeutic agent.
  - 135. A method of claim 120 wherein said toxicity is neurotoxicity.
  - 136. A method of claim 120 wherein said toxicity is nephrotoxicity.
  - 137. A method of claim 120 wherein said toxicity is myelosuppression.
  - 138. A method of claim 120 wherein said toxicity is hepatotoxicity.
  - 139. A method of claim 120 wherein said toxicity is nausea and emesis.
  - 140. A method of claim 120 wherein said method allows shorter duration between chemotherapeutic agent treatment cycles.
  - 141. A method of claim 120 wherein said method allows an increase in the dosage of the chemotherapeutic agent.
  - 142. A method of claim 120 wherein said method allows an increase in the number of chemotherapeutic treatments.
  - 143. A method of claim 120 further comprising administering a pre-therapy treatment at least one day prior to chemotherapy, prior to each chemotherapeutic treatment, immediately prior to each chemotherapy treatment, concomitantly with or simultaneously during chemotherapy treatment, immediately subsequent to chemotherapy, or subsequent to chemotherapy.
  - 144. A method of claim 120 wherein said chemotherapeutic agent is a taxane analog.
  - 145. A method of claim 120 wherein said chemotherapeutic agent is docetaxel.
  - 146. A method of claim 120 wherein said chemotherapeutic agent is paclitaxel.
  - 147. A method of claim 120 wherein said chemotherapeutic agent is a platinum analog.
  - 148. A method of claim 120 wherein said chemotherapeutic agent is cisplatin.
  - 149. A method of claim 120 wherein said chemotherapeutic agent is carboplatin.
  - 150. A method of claim 120 wherein said chemotherapeutic agent is oxaliplatin.
  - 151. A method of claim 120 wherein the chemotherapeutic agent is satraplatin.
  - 152. A method of claim 120 further comprising the administration of one or more chemotherapeutic agents.
  - 153. A method of claim 152, wherein said chemotherapeutic agents are selected from a group consisting of:
    - platinum analogs, and/or, taxanes and taxane analogs.
  - 154. A method of claim 120 additionally comprising one or more hydration steps.
  - 155. A method of claim 120 wherein said chemotherapeutic agent or agents is utilized for the treatment of a subject with lung cancer and adenocarcinoma.
  - 156. A method of claim 155 wherein said subject is human.
  - 157. A method of claim 120 wherein the 2,2′
    - -dithio-bis-ethane sulfonate is in a form suitable for oral administration.
  - 158. A method of claim 120 wherein the 2,2′
    - -dithio-bis-ethane sulfonate is in a form suitable for parenteral administration.
  - 159. A method of claim 157 wherein said 2,2′
    - -dithio-bis-ethane sulfonate is administered intravenously.

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Current Assignee
BioNumerik Pharmaceuticals, Inc.
Original Assignee
BioNumerik Pharmaceuticals, Inc.
Inventors
Hausheer, Frederick H.
Primary Examiner(s)
Weddington; Kevin E

Application Number

US11/638,193
Publication Number

US 20070135519A1
Time in Patent Office

1,749 Days
Field of Search

514/10, 514/100, 514/108, 514/449, 514/492
US Class Current

514/100
CPC Class Codes

A61K 31/185   Acids; Anhydrides, halides ...

A61K 31/255   of sulfoxy acids or sulfur ...

A61P 39/00   General protective or antin...

Chemoprotective methods and compositions

First Claim

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159 Claims

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Chemoprotective methods and compositions

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Abstract

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