Slow release formulations of cell cycle regulators and anti-cancer agents for local treatment of solid cancer
Provided herein are methods for treating cancer of a body cavity, including specifically urinary tract cancer, by way of at least one cell cycle regulator, and at least one anti-cancer drug for local treatment; wherein the therapeutic agents are embedded in, and slowly released from, a biocompatible hydrogel composition.
1. A method for treating a urinary tract cancer, comprising:
first administering to a subject in need thereof a first composition comprising a thermoreversible hydrogel composition and a therapeutically effective amount of at least one cell cycle modulator selected from the group consisting of hydroxyurea, alternol, resveratrol, fluorodeoxyuridine, thymidine dinucleotide pTpT and Zidovudine, PD-0332991, LEE011, CINK4, Flavopiridol p276-00 and P1446A-05; and
secondly administering to the subject a second composition comprising a thermoreversible hydrogel composition and a therapeutically effective amount of at least one chemotherapeutic agent selected from the group consisting of Mitomycin C, Apaziquone, Gemcitabine, Cisplatin, 5-FU (5-fluorouracil) Doxorubicin, Valrubicin, Epirubicin, Pirarubicin, and Methotrexate,
wherein the administration of the first and second compositions is by local administration to the urinary tract,
thereby treating the urinary tract cancer.
2. The method of claim 1 , wherein the urinary tract cancer is bladder cancer.
3. The method of claim 1 , wherein the thermoreversible hydrogel composition of the first and second compositions is the same.
4. The method of claim 1 , wherein the thermoreversible hydrogel compositions of the first and second compositions are different.
5. The method of claim 1 , wherein the thermoreversible hydrogel composition of the first and/or second compositions comprises:
20% to 40% (w/w) EPO/PPO block copolymer;
0.05% to 0.5% (w/w) hydroxypropylmethylcellulose (HPMC) or Polyvinylpyrrolidone (PVP);
0.1% to 2.5% (w/w) polyethylene glycol (PEG)-400;
and the balance water.
6. The method of claim 1 , wherein the cell cycle modulator is hydroxyurea.
7. The method of claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of: Mitomycin C, Gemcitabine, Cisplatin, and Doxorubicin.
8. The method of claim 1 , wherein the local administration is by intravesical instillation.
9. The method of claim 1 , wherein the second composition is administered to the subject 2-168 hours after administration of the first composition.
10. The method of claim 1 , wherein the first composition is allowed to remain in the urinary tract for at least 2 hours, and further comprising washing the first composition from the urinary tract prior to administration of the second composition.
11. The method of claim 10 , wherein the second composition is administered not more than 168 hours after the first composition is washed from the urinary tract.
12. The method claim 1 , wherein the first and second compositions are provided to the urinary tract following surgery to remove the cancer.
13. A method for treating a urinary tract cancer, comprising:
first administering to a subject in need thereof a first composition comprising a thermoreversible hydrogel composition and a therapeutically effective amount of hydroxyurea; and
secondly administering to the subject a second composition comprising a therapeutically effective amount of at least one chemotherapeutic agent selected from the group consisting of Mitomycin C, Cisplatin, Gemcitabine and doxorubicin,
wherein the administration of the first and second compositions is by local administration to the urinary tract, thereby treating the urinary tract cancer.
14. The method of claim 13 , wherein the first composition is allowed to remain in the urinary tract for at least 2 hours, and further comprising washing the first composition from the urinary tract prior to administration of the second composition.