FDG-pet evaluation of Ewing's sarcoma sensitivity
This invention relates to methods for evaluating the efficacy of an IGF1R inhibitor, such as an anti-IGF1R antibody, for the treatment of an Ewing's sarcoma tumor by determining the level of tumoral glucose metabolism. Tumoral glucose metabolism is determining at an early point in the treatment regimen by any of several methods known in the art including FDG-PET/CT scan.
1. A method for treating a Ewing's sarcoma tumor, in a subject, comprising evaluating glucose metabolism of the tumor after the subject has received a first dose of IGF1R inhibitor, but before a second dose of the inhibitor; or within 14 days of a first dose of IGF1R inhibitor but before a second dose of said inhibitor;
wherein treatment with the IGF1R inhibitor is discontinued if glucose metabolism does not significantly decrease or remain constant after said first dose;
and continuing treatment with the IGF1R inhibitor if glucose metabolism does significantly decrease or remain constant after said first dose; wherein the IGF1R inhibitor is an isolated antibody or antigen-binding fragment thereof comprising a light chain immunoglobulin comprising CDR1, CDR2 and CDR3 of an immunoglobulin light chain whose amino acid sequence is set forth in SEQ ID NO: 24; and, a heavy chain immunoglobulin comprising CDR1, CDR2 and CDR3 of an immunoglobulin heavy chain whose amino acid sequence is set forth in SEQ ID NO: 18.
2. The method of claim 1 wherein glucose metabolism is evaluated by administering labeled glucose and monitoring its metabolism by the tumor.
3. The method of claim 2 wherein glucose metabolism is evaluated by 18 F-fluorodeoxyglucose positron emission tomography.
4. The method of claim 1 wherein the Ewing's sarcoma is recurrent or relapsed Ewing's sarcoma.
5. The method of claim 1 wherein the subject is a human.
6. The method of claim 1 comprising continuing treatment with the IGF1R inhibitor if glucose metabolism decreases by about 15% to about 25% after said first dose.
7. The method of claim 1 wherein the IGF1R inhibitor is an isolated antibody.
8. The method of claim 7 wherein the antibody or fragment heavy and/or light chain variable region is linked to an immunoglobulin constant domain.
9. The method of claim 8 wherein immunoglobulin constant domain is selected from the group consisting of: kappa light chain, lambda light chain, gamma-1 heavy chain, gamma-2 heavy chain, gamma-3 heavy chain and gamma-4 heavy chain.
10. The method of claim 1 wherein the subject is administered an IGF1R antibody at a dose of about 1 to about 20 mg/kg every two weeks.
11. The method of claim 1 wherein the subject is administered an IGF1R antibody at a dose of about 10 mg/kg every two weeks.
12. The method of claim 1 wherein the subject is further administered a further chemotherapeutic agent.
13. The method of claim 12 wherein a further chemotherapeutic agent is
14. The method of claim 12 wherein a further chemotherapeutic agent is exemestane.
15. The method of claim 12 wherein a further chemotherapeutic agent is cyclophosphamide.
16. The method of claim 12 wherein a further chemotherapeutic agent is dactinomycin.
17. The method of claim 12 wherein a further chemotherapeutic agent is doxorubicin.
18. The method of claim 12 wherein a further chemotherapeutic agent is ifosfamide.
19. The method of claim 12 wherein a further chemotherapeutic agent is etoposide.
20. The method of claim 12 wherein a further chemotherapeutic agent is vincristine.
21. The method of claim 12 wherein a further chemotherapeutic agent is topotecan.