Compositions and methods of use of phorbol esters in the treatment of neoplasms

A method of treating neoplasms comprising administering parenterally to a mammalian subject with lymphoma, an effective amount of a phorbol ester of Formula I, or a pharmaceutically acceptable salt, isomer, enantiomer, solvate, hydrate, or polymorph thereof,

• wherein R1 and R2 are selected from the group consisting of hydrogen, hydroxyl,
• wherein the alkyl group contains 1 to 15 carbon atoms,
• wherein a lower alkenyl group contains between 1 to 7 carbon atoms,
• R3 is selected from hydrogen and
• wherein the lower alkyl group contains 1-7 carbon atoms;
• and
• optionally at least one secondary or adjunctive therapeutic agent;
• wherein said effective amount is between about 10 μg to about 1500 μg of said phorbol ester of Formula I, administered every other day and wherein said phorbol ester of Formula I is administered for at least a total of 5 times;
• and
• wherein one or more symptoms or conditions suffered by the mammalian subject is alleviated or treated, the one or more symptoms being selected from the group consisting of chronic fatigue, excessive or easy bleeding, easy bruising, shortness of breath, petechiae, recurrent fever, swollen gums, slow healing of cuts, bone and joint discomfort, recurrent infections, weight loss, itching, night sweats, lymph node swelling, fever, abdominal pain and discomfort, disturbances in vision, coughing, loss of appetite, pain in the chest, difficulty swallowing, swelling, a need to urinate frequently, difficulty starting urination, difficulty holding back urine, weak or interrupted flow of urine, painful or burning urination, difficulty in having an erection, painful ejaculation, blood in urine or semen, frequent pain or stiffness, and weakness.

A method of treating neoplasms comprising administering parenterally to a mammalian subject with breast cancer, an effective amount of a phorbol ester of Formula I, or a pharmaceutically acceptable salt, isomer, enantiomer, solvate, hydrate, or polymorph thereof,

• wherein R1 and R2 are selected from the group consisting of hydrogen, hydroxyl,
• wherein the alkyl group contains 1 to 15 carbon atoms,
• wherein a lower alkenyl group contains between 1 to 7 carbon atoms,
• R3 is selected from hydrogen and
• wherein the lower alkyl group contains 1-7 carbon atoms;
• and
• optionally at least one secondary or adjunctive therapeutic agent;
• wherein said effective amount is between about 10 μg to about 1500 μg of said phorbol ester of Formula I, administered every other day and wherein said phorbol ester of Formula I is administered for at least a total of 5 times;
• and
• wherein one or more symptoms or conditions suffered by the mammalian subject is alleviated or treated, the one or more symptoms being selected from the group consisting of chronic fatigue, excessive or easy bleeding, easy bruising, shortness of breath, petechiae, recurrent fever, swollen gums, slow healing of cuts, bone and joint discomfort, recurrent infections, weight loss, itching, night sweats, lymph node swelling, fever, abdominal pain and discomfort, disturbances in vision, coughing, loss of appetite, pain in the chest, difficulty swallowing, swelling, a need to urinate frequently, difficulty starting urination, difficulty holding back urine, weak or interrupted flow of urine, painful or burning urination, difficulty in having an erection, painful ejaculation, blood in urine or semen, frequent pain or stiffness, and weakness.

A method of treating neoplasms comprising administering parenterally to a mammalian subject with liver cancer, an effective amount of a phorbol ester of Formula I, or a pharmaceutically acceptable salt, isomer, enantiomer, solvate, hydrate, or polymorph thereof,

• wherein R1 and R2 are selected from the group consisting of hydrogen, hydroxyl,
• wherein the alkyl group contains 1 to 15 carbon atoms,
• wherein a lower alkenyl group contains between 1 to 7 carbon atoms,
• R3 is selected from hydrogen and
• wherein the lower alkyl group contains 1-7 carbon atoms;
• and
• optionally at least one secondary or adjunctive therapeutic agent;
• wherein said effective amount is between about 10 μg to about 1500 μg of said phorbol ester of Formula I, administered every other day and wherein said phorbol ester of Formula I is administered for at least a total of 5 times;
• and
• wherein one or more symptoms or conditions suffered by the mammalian subject is alleviated or treated, the one or more symptoms being selected from the group consisting of chronic fatigue, excessive or easy bleeding, easy bruising, shortness of breath, petechiae, recurrent fever, swollen gums, slow healing of cuts, bone and joint discomfort, recurrent infections, weight loss, itching, night sweats, lymph node swelling, fever, abdominal pain and discomfort, disturbances in vision, coughing, loss of appetite, pain in the chest, difficulty swallowing, swelling, a need to urinate frequently, difficulty starting urination, difficulty holding back urine, weak or interrupted flow of urine, painful or burning urination, difficulty in having an erection, painful ejaculation, blood in urine or semen, frequent pain or stiffness, and weakness.

A method of treating neoplasms comprising administering parenterally to a mammalian subject with pancreatic cancer, an effective amount of a phorbol ester of Formula I, or a pharmaceutically acceptable salt, isomer, enantiomer, solvate, hydrate, or polymorph thereof,

• wherein R1 and R2 are selected from the group consisting of hydrogen, hydroxyl,
• wherein the alkyl group contains 1 to 15 carbon atoms,
• wherein a lower alkenyl group contains between 1 to 7 carbon atoms,
• R3 is selected from hydrogen and
• wherein the lower alkyl group contains 1-7 carbon atoms;
• and
• optionally at least one secondary or adjunctive therapeutic agent;
• wherein said effective amount is between about 10 μg to about 1500 μg of said phorbol ester of Formula I, administered every other day and wherein said phorbol ester of Formula I is administered for at least a total of 5 times;
• and
• wherein one or more symptoms or conditions suffered by the mammalian subject is alleviated or treated, the one or more symptoms being selected from the group consisting of chronic fatigue, excessive or easy bleeding, easy bruising, shortness of breath, petechiae, recurrent fever, swollen gums, slow healing of cuts, bone and joint discomfort, recurrent infections, weight loss, itching, night sweats, lymph node swelling, fever, abdominal pain and discomfort, disturbances in vision, coughing, loss of appetite, pain in the chest, difficulty swallowing, swelling, a need to urinate frequently, difficulty starting urination, difficulty holding back urine, weak or interrupted flow of urine, painful or burning urination, difficulty in having an erection, painful ejaculation, blood in urine or semen, frequent pain or stiffness, and weakness.

A method of treating neoplasms comprising administering parenterally to a mammalian subject with cervical cancer, an effective amount of a phorbol ester of Formula I, or a pharmaceutically acceptable salt, isomer, enantiomer, solvate, hydrate, or polymorph thereof,

• wherein R1 and R2 are selected from the group consisting of hydrogen, hydroxyl,
• wherein the alkyl group contains 1 to 15 carbon atoms,
• wherein a lower alkenyl group contains between 1 to 7 carbon atoms,
• R3 is selected from hydrogen and
• wherein the lower alkyl group contains 1-7 carbon atoms;
• and
• optionally at least one secondary or adjunctive therapeutic agent;
• wherein said effective amount is between about 10 μg to about 1500 μg of said phorbol ester of Formula I, administered every other day and wherein said phorbol ester of Formula I is administered for at least a total of 5 times;
• and
• wherein one or more symptoms or conditions suffered by the mammalian subject is alleviated or treated, the one or more symptoms being selected from the group consisting of chronic fatigue, excessive or easy bleeding, easy bruising, shortness of breath, petechiae, recurrent fever, swollen gums, slow healing of cuts, bone and joint discomfort, recurrent infections, weight loss, itching, night sweats, lymph node swelling, fever, abdominal pain and discomfort, disturbances in vision, coughing, loss of appetite, pain in the chest, difficulty swallowing, swelling, a need to urinate frequently, difficulty starting urination, difficulty holding back urine, weak or interrupted flow of urine, painful or burning urination, difficulty in having an erection, painful ejaculation, blood in urine or semen, frequent pain or stiffness, and weakness.

A method of treating neoplasms comprising administering parenterally to a mammalian subject with multiple myeloma, an effective amount of a phorbol ester of Formula I, or a pharmaceutically acceptable salt, isomer, enantiomer, solvate, hydrate, or polymorph thereof,

• wherein R1 and R2 are selected from the group consisting of hydrogen, hydroxyl,
• wherein the alkyl group contains 1 to 15 carbon atoms,
• wherein a lower alkenyl group contains between 1 to 7 carbon atoms,
• R3 is selected from hydrogen and
• wherein the lower alkyl group contains 1-7 carbon atoms;
• and
• optionally at least one secondary or adjunctive therapeutic agent;
• wherein said effective amount is between about 10 μg to about 1500 μg of said phorbol ester of Formula I, administered every other day and wherein said phorbol ester of Formula I is administered for at least a total of 5 times;
• and
• wherein one or more symptoms or conditions suffered by the mammalian subject is alleviated or treated, the one or more symptoms being selected from the group consisting of chronic fatigue, excessive or easy bleeding, easy bruising, shortness of breath, petechiae, recurrent fever, swollen gums, slow healing of cuts, bone and joint discomfort, recurrent infections, weight loss, itching, night sweats, lymph node swelling, fever, abdominal pain and discomfort, disturbances in vision, coughing, loss of appetite, pain in the chest, difficulty swallowing, swelling, a need to urinate frequently, difficulty starting urination, difficulty holding back urine, weak or interrupted flow of urine, painful or burning urination, difficulty in having an erection, painful ejaculation, blood in urine or semen, frequent pain or stiffness, and weakness.