Use of metallocene compounds for cancer treatment

1. A method of treating cancer in a subject in need thereof, comprising administering to the subject a composition comprising a therapeutically effective amount of a metallocene compound, and optionally a pharmaceutically acceptable diluent, excipient, or carrier; wherein the metallocene compound has the structure of formula CPH-1, CPH-2, CPH-3, CPH-4, CPH-5, CPH-6, CPH-7, CPH-8, CPH-9, CPH-10, CPH-11, CPH-12, CPH-13, CPH-14, or CPH-15, or a pharmaceutically acceptable salt thereof:

wherein the cancer is melanoma, lung, colon, urinary bladder, breast, renal, prostate, ovarian, cervical, or head and neck cancer.

2. A method of treating cancer in a subject in need thereof, comprising administering to the subject a composition comprising:

a therapeutically effective amount of a metallocene compound having formula MET-B, or a pharmaceutically acceptable salt thereof:

and

optionally a pharmaceutically acceptable diluent, excipient, or carrier; wherein:

M is Ti, Zr, or Hf;

each R X , R Y , and R Z independently is H, a halide, hydrocarbyl group, or halogenated hydrocarbyl group;

E 1 is C or Si;

R 1 and R 2 are independently H or a hydrocarbyl group, or halogenated hydrocarbyl group;

X 1 and X 2 are independently a monoanionic ligand; and

q, r, and s are independently 0, 1, 2, 3, or 4; and

wherein the cancer is melanoma, lung, colon, urinary bladder, breast, renal, prostate, ovarian, cervical, or head and neck cancer.

3. The method of claim 2 , wherein the cancer is resistant or insensitive to treatment with one or more of alemtuzumab, aminoglutethimide, anastrozole, asparginase, bacillus calmette-guerin, bendamustine, bevacizumab, bicalutamide, bleomycin, bortezomib, brentuximab, cabazitaxel, capecitabine, carboplatin, carmustine, cervarix, cetuximab, cisplatin, cyclophosphamide, cytarabine, dacarbazine, dasatinib, daunorubicin, desarelix, dexamethasone, docetaxel, doxil, doxorubicin, epirubicin, erlotinib, etoposide, everolimus, exemestane, fadrozole, fludarabine, 5-fluorouracil, flutamide, fulvestrant, gardasil, gemcitabine, goserelin, ibritumomab, idarubicin, ifosfamide, il-2, imatinib, inlyta, interferon-alpha, ipilimumab, irinotecan, ixabepilone, lapatinib, lenalidomide, letrozole, leucovorin, leuprolide, lomustine, megestrol acetate, melphalan, methotrexate, 6-mercaptopurine, mitomycin-C, mitoxantrone, nilotinib, nilutamide, oxaliplatin, paclitaxel, panitumumab, pazopanib, pegasparginase, pemetrexed, procarbazine, raloxifene, rituximab, sorafenib, sunitinib, sylatron (Peg), tamoxifen, temozolomide, temsirolimus, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, vemurafenib, vincristine, vinorelbine, vismodegib, and/or vorinostat.

4. The method of claim 2 , wherein the cancer is resistant or insensitive to treatment with a platinum agent.

5. The method of claim 2 , wherein the cancer is resistant or insensitive to treatment with a taxane.

6. The method of claim 1 , wherein the subject is a human.

7. The method of claim 2 , wherein:

M is Zr or Hf; or

at least one R X , R Y , or R Z is a C 1 to C 8 alkyl or C 3 to C 8 alkenyl group; or

E 1 is C; or

at least one of R 1 and R 2 is an alkyl, alkenyl, or phenyl; or

q, r, and s are independently 0, 1, or 2; or

any combination thereof.

8. The method of claim 2 , wherein:

M is Zr or Hf;

at least one R X , R Y , or R Z is a C 1 to C 8 alkyl or C 3 to C 8 alkenyl group;

E 1 is C;

at least one of R 1 and R 2 is a phenyl group or an alkenyl group;

q, r, and s are independently 0 or 1; and

at least one of X 1 and X 2 is Cl.

9. The method of claim 2 , wherein the composition is administered in combination with a therapeutically effective amount of a therapeutic agent, the therapeutic agent comprising alemtuzumab, aminoglutethimide, anastrozole, asparginase, bacillus calmette-guerin, bendamustine, bevacizumab, bicalutamide, bleomycin, bortezomib, brentuximab, cabazitaxel, capecitabine, carboplatin, carmustine, cervarix, cetuximab, cisplatin, cyclophosphamide, cytarabine, dacarbazine, dasatinib, daunorubicin, desarelix, dexamethasone, docetaxel, doxil, doxorubicin, epirubicin, erlotinib, etoposide, everolimus, exemestane, fadrozole, fludarabine, 5-fluorouracil, flutamide, fulvestrant, gardasil, gemcitabine, goserelin, ibritumomab, idarubicin, ifosfamide, il-2, imatinib, inlyta, interferon-alpha, ipilimumab, irinotecan, ixabepilone, lapatinib, lenalidomide, letrozole, leucovorin, leuprolide, lomustine, megestrol acetate, melphalan, methotrexate, 6-mercaptopurine, mitomycin-C, mitoxantrone, nilotinib, nilutamide, oxaliplatin, paclitaxel, panitumumab, pazopanib, pegasparginase, pemetrexed, procarbazine, raloxifene, rituximab, sorafenib, sunitinib, sylatron (Peg), tamoxifen, temozolomide, temsirolimus, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, vemurafenib, vincristine, vinorelbine, vismodegib, vorinostat, or a mixture thereof.

10. The method of claim 9 , wherein the therapeutic agent comprises bevacizumab, dacarbazine, docetaxel, 5-fluorouracil, gemcitabine, ipilimumab, paclitaxel, or a mixture thereof.

11. The method of claim 9 , wherein the therapeutically effective amount of the metallocene compound administered in combination with the therapeutically effective amount of the therapeutic agent results in a synergistic increase in cytotoxicity.

12. The method of claim 6 , wherein the cancer is melanoma.

13. The method of claim 6 , wherein the cancer is ovarian cancer.

14. The method of claim 6 , wherein the cancer is lung, colon, urinary bladder, renal, prostate, or head and neck cancer.

15. The method of claim 6 , wherein the cancer is breast or cervical cancer.

16. The method of claim 2 , wherein the subject is a human.

17. The method of claim 16 , wherein the cancer is melanoma.

18. The method of claim 16 , wherein the cancer is ovarian cancer.

19. The method of claim 16 , wherein the cancer is lung, colon, urinary bladder, renal, prostate, or head and neck cancer.

20. The method of claim 16 , wherein the cancer is breast or cervical cancer.