Method for identification of sensitivity of a patient to telomerase inhibition therapy
The invention provides methods for determining the susceptibility of cancer patients to developing adverse reactions if treated with a telomerase inhibitor drug by measurement of telomere length in appropriate cells of the patient prior to initiation of the telomerase inhibitor treatment.
1. A method to treat a patient with a telomerase inhibitor comprising:
(a) determining the average or median telomere length in a biological sample comprising non-cancerous white blood cells obtained from the mammalian subject prior to or at the time of treatment with the telomerase inhibitor and multiplying the average or median telomere length by a coefficient to arrive at a telomere length component;
(b) multiplying the intended treatment dosage of telomerase inhibitor by a coefficient to arrive at a dosage component;
(c) calculating the sum of the telomere component, the dosage component and the log of the subject's baseline platelet number to determine the predicted platelet nadir during the first weeks of treatment;
(d) determining that there is an expected likelihood of an adverse reaction in a patient from treatment with the telomerase inhibitor; and
(e) administering a reduced dose of the telomerase inhibitor or administering a reduced dosage regimen of the telomerase inhibitor or administering an ameliorating pharmaceutical.
2. The method of claim 1 , wherein the patient is a human.
3. The method of claim 1 , wherein the adverse reaction is selected from at least one of thrombocytopenia, anemia, leucopenia, and neutropenia.
4. The method of claim 3 , wherein the adverse reaction is thrombocytopenia and the sum of the telomere component, the dosage component and the constant determines the percentage decrease of the patient's platelet number from the patient's platelet number prior to treatment.
5. The method of claim 1 , wherein the white blood cells are selected from at least one of granulocytes, lymphocytes, monocytes and macrophages.
6. The method of claim 5 , wherein the granulocytes are neutrophils, basophils or eosinophils.
7. The method of claim 5 , wherein the blood cells are selected from at least one of lymphocytes, monocytes and macrophages.
8. The method of claim 1 , wherein the telomerase inhibitor is an oligonucleotide.
9. The method of claim 1 , wherein the telomerase inhibitor is GRN163L.
10. The method of claim 9 , wherein the dosage regimen of GRN163L comprises administration of at least about 1.6 mg/kg to about 20 mg/kg of GRN163L on day 1 and on approximately day 8 of a 21 day cycle.
11. The method of claim 9 , wherein the dosage regimen of GRN163L comprises administration of at least about 1.6 mg·kg to about 20 mg/kg of GRN163L on day 1 and on approximately day 15 of a 28 day cycle.
12. The method of claim 1 , wherein the patient is being treated for cancer.
13. The method of claim 12 , wherein the cancer is selected from the group consisting of breast cancer, colon cancer, lung cancer, prostate cancer, testicular cancer, hepatocellular cancer, gastric cancer, gastrointestinal cancer, pharynx cancer, rectal cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, cancer of the urinary tract, thyroid cancer, renal cancer, skin cancer, brain cancer, carcinoma, melanoma, leukemia and lymphoma.
14. The method of claim 1 , wherein the telomere length component is a positive component when calculating the percentage change.
15. The method of claim 1 , wherein the dosage component is a negative component when calculating the percentage change.
16. The method of claim 1 , wherein the method further comprises the step of assigning to the subject the likelihood of having an adverse reaction to a telomerase inhibitor therapy.
17. The method of claim 1 , wherein, the baseline telomere length is determined by FISH analysis.