Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine
A combination of a 4-anilino-3-cyanoquinoline compound (e.g. HKI-272, SKI-606, EKB-569) and a capecitabine compound in the treatment of a neoplasm is provided. Regimens, kits, and methods for treatment of neoplasm, including breast cancer including metastatic breast cancer, and lung cancer, using this combination, optionally in combination with other anti-neoplastic agents, or immune modulators are also described.
1. A method for treating an ErbB-2 positive metastatic breast cancer in a subject; comprising administering to the subject neratinib and capecitabine; wherein neratinib and capecitabine act synergistically.
2. The method of claim 1 , wherein the breast cancer is a locally advanced breast cancer.
3. The method according to claim 1 , wherein one or both of capecitabine and neratinib is administered in a subtherapeutically effective amount.
4. The method according to claim 1 , wherein neratinib and capecitabine are administered orally.
5. The method according to claim 1 , wherein neratinib and capecitabine are administered concurrently, sequentially, simultaneously, in a specified order, or according to a specific temporal relationship.
6. The method according to claim 1 , wherein neratinib is administered in a unit dose.
7. The method according to claim 6 , wherein capecitabine is administered in a unit dose.
8. The method according to claim 1 , wherein capecitabine is administered in an amount of about 1250 mg to about 3000 mg daily.
9. The method according to claim 1 , wherein capecitabine is administered at least once over a period of 21 days.
10. The method according to claim 1 , wherein the administration of capecitabine is continued for 3 to 6 cycles.
11. The method according to claim 1 , wherein neratinib is administered in an amount of at least 40 mg per day.
12. The method according to claim 11 , wherein neratinib is administered in an amount of at least 120 mg per day.
13. The method according to claim 12 , wherein neratinib is administered in an amount of at least 240 mg per day.
14. The method according to claim 1 , wherein neratinib is administered daily.
15. The method according to claim 1 , wherein neratinib is administered at least once daily.
16. The method according to claim 1 , wherein neratinib is administered for at least 2 continuous weeks.
17. The method according to claim 1 , wherein neratinib is administered before capecitabine.
18. The method according to claim 1 , wherein neratinib is administered after capecitabine.
19. The method according to claim 1 , wherein neratinib and capecitabine are administered simultaneously.
20. The method according to claim 1 , wherein administration of capecitabine is discontinued after about 24 weeks.
21. The method of claim 1 , wherein neratinib is administered in a dose range of about 20 to about 240 mg per day.
22. The method of claim 1 , wherein the subject is a human.
23. A method for treating an ErbB-2 positive metastatic breast cancer in a subject, wherein one treatment cycle comprises 21 days, comprising:
(a) orally administering to the subject at least one unit dose of neratinib daily starting on day 1 of said cycle; and
(b) orally administering to the subject at least one a unit dose of capecitabine on days 1 to 14 of said cycle;
wherein neratinib and capecitabine act synergistically.