Methods of treatment
The present disclosure provides for methods of treating a patient with a CYP3A4 substrate drug, wherein the patient is treated with posaconazole. In some embodiments, the patient stops posaconazole treatment, waits for at least 2 days, and then is treated with the CYP3A4 substrate drug as soon as it is safe to do so. In some embodiments, treatment with the CYP3A4 substrate drug is delayed for about 2-42 days after stopping posaconazole. In some embodiments, the patient is treated with a reduced dose of the CYP3A4 substrate drug for about 2-42 days.
1. A method of treating a cancer with a BRAF V600E or V600K mutation in a patient in need thereof, with an antineoplastic drug which is a CYP3A4 substrate, wherein the patient is treated with a strong CYP3A4 inhibitor, comprising:
(a) stopping the strong CYP3A4 inhibitor treatment;
(b) delaying administering, for at least about 3 days after stopping the strong CYP3A4 inhibitor treatment, a dose of the antineoplastic drug that the patient would have received based on the age and condition of the patient if the patient had not been treated with the strong CYP3A4 inhibitor; and then
(c) administering the dose of the antineoplastic drug that the patient would have received based on the age and condition of the patient if the patient had not been treated with the strong CYP3A4 inhibitor,
wherein the strong CYP3A4 inhibitor is posaconazole.
2. The method of claim 1 , wherein the patient is not obese.
3. The method of claim 1 , wherein said administering in step (c) is about 3-11 days after stopping the strong CYP3A4 inhibitor in step (a).
4. The method of claim 1 , wherein said administering in step (c) is about 3 days after stopping the strong CYP3A4 inhibitor in step (a).
5. The method of claim 1 , wherein said administering in step (c) is about 4 days after stopping the strong CYP3A4 inhibitor in step (a).
6. The method of claim 1 , wherein said administering in step (c) is about 5 days after stopping the strong CYP3A4 inhibitor in step (a).
7. The method of claim 1 , wherein said administering in step (c) is about 6 days after stopping the strong CYP3A4 inhibitor in step (a).
8. The method of claim 1 , wherein said administering in step (c) is about 7 days after stopping the strong CYP3A4 inhibitor in step (a).
9. The method of claim 1 , wherein said administering in step (c) is about 8 days after stopping the strong CYP3A4 inhibitor in step (a).
10. The method of claim 1 , wherein said administering in step (c) is about 9 days after stopping the strong CYP3A4 inhibitor in step (a).
11. The method of claim 1 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
12. The method of claim 2 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
13. The method of claim 3 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
14. The method of claim 4 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
15. The method of claim 5 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
16. The method of claim 6 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
17. The method of claim 7 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
18. The method of claim 8 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
19. The method of claim 9 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
20. The method of claim 10 , wherein the cancer is metastatic melanoma with a BRAF V600E or V600K mutation.
21. The method of claim 1 , wherein the patient has at least one characteristic selected from the group consisting of the following:
i) BMI of at least about 35;
ii) waist size greater than about 42 inches;
iii) % body fat greater than about 40%;
iv) total body fat greater than about 40 kg; and
v) medically diagnosed as obese.
22. The method of claim 1 , wherein said administering in step (c) is about 10 days after stopping the strong CYP3A4 inhibitor in step (a).
23. The method of claim 1 , wherein said administering in step (c) is about 11 days after stopping the strong CYP3A4 inhibitor in step (a).
24. A method of treating a disease selected from the group consisting of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer; HER2-negative breast cancer; metastatic pancreatic cancer; and metastatic castration-resistant prostate cancer, in a patient in need of treatment with a CYP3A4 substrate drug, wherein the patient is treated with a strong CYP3A4 inhibitor, comprising:
(a) stopping the strong CYP3A4 inhibitor treatment;
(b) delaying administering, for at least about 3 days after stopping the strong CYP3A4 inhibitor treatment, a dose of the CYP3A4 substrate drug that the patient would have received based on the age and condition of the patient if the patient had not been treated with the strong CYP3A4 inhibitor; and then
(c) administering the dose of the CYP3A4 substrate drug that the patient would have received based on the age and condition of the patient if the patient had not been treated with the strong CYP3A4 inhibitor,
wherein the CYP3A4 inhibitor is posaconazole and the CYP3A4 substrate drug is olaparib.
25. The method of claim 24 , wherein the disease is germline BRCA-mutated (gBRCAm) advanced ovarian, fallopian tube, or primary peritoneal cancer.
26. The method of claim 24 , wherein the disease is germline BRCA-mutated (gBRCAm) HER2-negative breast cancer.
27. The method of claim 24 , wherein the patient is not obese.
28. The method of claim 24 , wherein the patient has at least one characteristic selected from the group consisting of the following:
i) BMI of at least about 35;
ii) waist size greater than about 42 inches;
iii) % body fat greater than about 40%;
iv) total body fat greater than about 40 kg; and
v) medically diagnosed as obese.
29. The method of claim 24 , wherein said administering in step (c) is about 3-11 days after stopping the strong CYP3A4 inhibitor in step (a).
30. The method of claim 24 , wherein said administering in step (c) is about 3-9 days after stopping the strong CYP3A4 inhibitor in step (a).
31. The method of claim 1 , wherein the CYP3A4 substrate drug is cobimetinib.