Molecular markers for prediction of drug efficacy and toxicity before chemotherapy

  Recently, a male patient was admitted. The patient was post-operative pathology of rectal adenocarcinoma after radical rectal cancer surgery in March last year, stage T4aN1M0 IIIA, immunohistochemistry: EGFR(-), ERCC(++), TS(++), VEGF(+++), COX(+++), ki-67 about 80%.  He was given FOLOFOX4 regimen chemotherapy in a hospital oncology department in two-week cycles. 8 cycles of chemotherapy later, a repeat CT suggested multiple metastases in the liver. The patient was changed to standard FOLFIRI regimen chemotherapy. On the 6th day after the first cycle of chemotherapy, the patient’s diarrhea was significantly aggravated and improved after more than 10 days of treatment. The doctor suggested to stop chemotherapy and go to radiotherapy department for radiotherapy of liver metastases. After the completion of radiotherapy, he returned to the oncology department and was given pemetrexed chemotherapy for 2 cycles and then rechecked, and the liver lesion increased.  The following points need attention: 1. ERCC (++) suggests insensitivity to platinum (some experts believe that the value of sensitivity to oxaliplatin drug is less than cisplatin), TS (++) suggests insensitivity to fluorouracil class, which is not difficult to explain why the patient is not effective to FOLOFOX4. TS (++) also suggests poor sensitivity to pemetrexed.  2. Changing to standard FOLFIRI regimen chemotherapy, the patient had significant diarrhea. If the patient had been given UTG1A1 gene polymorphism testing in advance, diarrhea might have been avoided or given prompt treatment. After this patient was admitted to the hospital, we gave the UTG1A1 gene polymorphism test and found that the patient was a high-risk group for irinotecan-associated diarrhea.  3. Some physicians need to increase their awareness of this and not mislead their patients. There was a patient, whom we asked to test for UTG1A1 gene polymorphism, refused to test with the excuse that he did not have money. After using irinotecan, diarrhea was obvious, just in time for the company to be free, and after the test, it was found that he was prone to diarrhea, for which the patient had a big fight with his son, and the patient said that his son was unfilial, and his son complained to the doctor, “saying that it was said by some famous doctor in another hospital that it was useless to do genetic testing”. Subsequently, we adjusted the usage of irinotecan and gave prophylaxis, and no further diarrhea occurred and the disease was controlled.  4. Clinically, most chemotherapeutic drugs have corresponding drug sensitivity markers, and many of them have been recognized by experts.  Although, there are many deficiencies in the current chemotherapy drug sensitivity markers, since they are available, they need attention. With the improvement of detection technology, we have noticed in our clinical work that there is a good correlation between these markers and patients’ treatment response.