A 66-year-old man was referred to our hospital for treatment of his thoracic eso

Question

A 66-year-old man was referred to our hospital for treatment of his thoracic esophageal cancer An irregularly elevated lesion occupied the middle thoracic esophagus, and biopsy specimens from the lesion showed well-differentiated squamous cell carcinoma. Computed tomography revealed wall thickening in the middle thoracic esophagus and swelling of a middle thoracic para-esophageal lymph node. 18F-fluorodeox Font Size e positron emission tomography computed tomography revealed high uptake at the tumor and lymph node. We diagnosed the cancer as clinical stage lIB according to the Union for International Cancer Control (UICC) classification. The patient underwent neoadjuvant chemotherapy consisting of 80 mg/m cisplatin on day 1 and 800 mg/m 5-fluorouracil on days 1-5. On day 5, however, the patient's serum creatinine level had increased to 7.83 mg/ml. We diagnosed grade 4 acute renal failure based on the Common Terminology Criteria for Adverse Events, after which chemotherapy was stopped, and the patient was administered hemodialysis without delay. On day 36, we performed a renal biopsy, and the specimen contained 24 glomeruli, 3 of which were sclerotic. Light microscopy showed no mesangial proliferation. There was diffuse moderate interstitial infiltration of lymphocytes with tubulitis, mild interstitial fibrosis, and mild arteriolar sclerosis Tubular casts without macrophagic reactions were seen. The patient's renal function was expected to recover, but after 2 months of hemodialysis it had not. We therefore decided to resume treatment of his esophageal cancer while continuing hemodailysis. At that time, the patient was suffering from congestive heart failure and interstitial pneumonia, so we administered definitive radiotherapy (60 Gy). It is 48 months since the radiotherapy, and the patient is currently alive without recurrence of his esophageal cancer 0 9 1. What chemotherapeutic drug that most likely triggered the impaired renal function? 2. Explain the mechanism of action of the 2 drugs administered for cancer treatment. 3. Based on the drugs action, describe what cells are mostly targeted? 4. Which one of the 10 hallmarks of cancer do both the drugs target the most?

Explanation / Answer

1. Some chemotherapy drugs can damage the renal system. Kidney is the place where the metabolism occurs for few chemotherapy drugs. As chemotherapy drugs break down the residual products damage kidney, ureters and bladder. In the above scenario it is the cisplatin that has triggered impaired renal function

2. Cisplatin interferes with DNA replication, which kills the fastest proliferating cells, which are carcinogenic

5- fluorouracil works in several ways, primarily as a thymidylate sunshade inhibitor which interrupt the synthesis of primitive thymidineby blocking the enzyme which is a nucleoside required for DNA replication

3. Cisplatin targets those cells that are diving at a abnormal rate. 5-fluorouracil target the cell cycle and stops DNA production

4. Evading apoptosis is the one hallmark that both drugs target the most

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