METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER WITH 5-IODO-2-PYRIMIDINONE-2(prime)-DEOXYRIBOSE (IPdR)

Abstract

Provided are methods of treating a human patient having cancer by administering IPdR to the patient in the form of an oral drug and administering radiation therapy (RT) to the patient. The method can also include administering a chemotherapeutic drug or biologic agent to the patient. Also provided are methods for optimizing IPdR sensitization for radiation therapy for a cancer patient having been administered IPdR.

What is claimed is: 
     
         1 . A method of treating a human patient having cancer, the method comprising the steps of:
 administering IPdR to the patient in the form of an oral drug; and   administering radiation therapy (RT) to the patient.   
     
     
         2 . The method of  claim 1 , wherein RT is administered via a hyperfractionated technique. 
     
     
         3 . The method of  claim 1 , wherein the patient cannot tolerate the optimum RT field without the addition of IPdR. 
     
     
         4 . The method of  claim 1 , wherein the technique of RT delivery is selected from the group of: 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, image-guided radiation therapy, tomotherapy, stereotactic radiosurgery and stereotactic body radiation therapy. 
     
     
         5 . The method of  claim 1 , wherein the source of RT is selected from the group consisting of: protons and carbon ions. 
     
     
         6 . The method of  claim 1 , wherein the cancer is MMR-deficient. 
     
     
         7 . The method of  claim 1  further comprising the step of:
 administering a chemotherapeutic drug or biologic agent to the patient prior to administering radiation therapy (RT) to the patient. 
 
     
     
         8 . The method of  claim 7 , wherein the chemotherapeutic drug is selected from the group consisting of a fluoropyrimidine, a platinum analog, a ribonucleotide reductase inhibitor and a methylating agent. 
     
     
         9 . The method of  claim 7 , wherein the biologic agent is a BER modulator. 
     
     
         10 . The method of  claim 7 , wherein the cancer is BER-deficient. 
     
     
         11 . The method of  claim 1 , wherein the IPdR is administered at a dose of 0.1-50 gm/M2/day. 
     
     
         12 . A method of optimizing IPdR sensitization for radiation therapy for a cancer patient having been administered IPdR, the method comprising:
 determining an IUdR-DNA incorporation level in a first tumor biopsy taken from the patient;   determining an IUdR-DNA incorporation level in a normal tissue sample; and   calculating a therapeutic index;   wherein the therapeutic index guides dose and schedule of radiation therapy.   
     
     
         13 . The method of  claim 12 , wherein the therapeutic index is calculated by dividing the percent IUdR-DNA incorporation level in the first tumor biopsy by the percent IUdR-DNA incorporation of the normal tissue sample. 
     
     
         14 . The method of  claim 12 , wherein IUdR-DNA incorporation levels are measured by high performance liquid chromatography (HPLC) or flow cytometry. 
     
     
         15 . The method of  claim 12 , comprising determining an IUdR-DNA incorporation level in a second tumor biopsy taken at a second time from the patient, determining an IUdR-DNA incorporation level in a normal tissue sample; and calculating a therapeutic index.