Treatment of prostate cancer
Methods for treating prostate cancer, including advanced prostate cancer, in a subject in need thereof, include administering once-daily to the subject, at least 80 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof. Another method includes: administering once-daily to the subject in need thereof, an oral load dose formulation having from 240 mg to 480 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof; and thereafter administering once-daily to the subject, an oral maintenance dose formulation having 80 mg to 160 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof.
1. A method of treating prostate cancer in a subject in need thereof, the method comprising:
(i) orally administering a loading dose of 360 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject; and
(ii) about one day after administering the loading dose, orally administering 120 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject once a day;
wherein the subject's serum testosterone concentration is below 50 ng/dL by day 8 of the treatment.
2. The method of claim 1 , wherein the subject's serum testosterone concentration is below 50 ng/dL by day 4 of treatment.
3. The method of claim 2 , wherein the subject's serum testosterone concentration is below 50 ng/dL within 24 to 48 hours after commencing treatment.
4. The method of claim 1 , wherein the subject's serum testosterone concentration is below 20 ng/dL from weeks 5 to 48 of treatment.
5. The method of claim 1 , wherein the subject's serum testosterone concentration is below 20 ng/dL within five weeks of commencing treatment.
6. The method of claim 1 , wherein the subject's serum testosterone concentration is below 20 ng/dl within three weeks after commencing treatment.
7. The method of claim 1 , wherein the subject's serum testosterone concentration is below 20 ng/dL within two weeks after commencing treatment.
8. The method of claim 1 , wherein the subject's serum testosterone concentration is below 20 ng/dL within one week after commencing treatment.
9. The method of claim 1 , wherein the subject's serum testosterone concentration is below 20 ng/dL within 4 days after commencing treatment.
10. The method of claim 2 , wherein the subject's serum testosterone concentration is below 20 ng/dL from weeks 5 to 48 of treatment.
11. The method of claim 2 , wherein the subject's serum testosterone concentration is below 20 ng/dL within five weeks of commencing treatment.
12. The method of claim 2 , wherein the subject's serum testosterone concentration is below 20 ng/dL within three weeks after commencing treatment.
13. The method of claim 2 , wherein the subject's serum testosterone concentration is below 20 ng/dL within two weeks after commencing treatment.
14. The method of claim 2 , wherein the subject's serum testosterone concentration is below 20 ng/dL within one week after commencing treatment.
15. The method of claim 1 , further comprising:
(iii) discontinuing administering N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject,
wherein the subject's serum testosterone concentration is at least about 280 ng/dL within about 90 days after discontinuing.
16. The method of claim 15 , wherein the subject's serum testosterone concentration is at least about 280 ng/dL within about 8 weeks after discontinuing.
17. The method of claim 15 , wherein the subject's serum testosterone concentration is at least about 280 ng/dL within about 4 weeks after discontinuing.
18. The method of claim 2 , further comprising:
(iii) discontinuing administering N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject,
wherein the subject's serum testosterone concentration is at least about 280 ng/dl within about 90 days after discontinuing.
19. The method of claim 18 , wherein the subject's serum testosterone concentration is at least about 280 ng/dL within about 8 weeks after discontinuing.
20. The method of claim 18 , wherein the subject's serum testosterone concentration is at least about 280 ng/dL within about 4 weeks after discontinuing.