Pharmacokinetics of cisplatin in an esophageal cancer patient on hemodialysis who was treated with a full-dose cisplatin-fluorouracil regimen: A case report.

INTRODUCTION: Cancer patients undergoing hemodialysis might be under-treated because the pharmacokinetics of anti-cancer drugs in such patients remain unknown and out of concern related to the potential development of severe adverse effects. However, patients with chemosensitive cancer, such as esophageal cancer, should receive chemotherapy at a dose that is sufficient to attain a favorable therapeutic effect. We herein present an interesting case involving an esophageal cancer patient who was successfully treated with subtotal thoracic esophagectomy, and adjuvant full-dose chemotherapy with cisplatin and 5-fluorouracil while concomitantly undergoing hemodialysis. We carried out a pharmacokinetics analysis of cisplatin, and also conducted a systematic review on the dose and pharmacokinetics. CASE REPORT: A 57-year-old male patient with esophageal cancer who was undergoing hemodialysis was referred to our hospital. He underwent subtotal thoracic esophagectomy. The pathological diagnosis was T1b, N2 (5/26), M0, ly2, v2, stage IIIA (Union for International Cancer Control, 8th edition). Because of the high degree of lymph node metastasis, adjuvant chemotherapy with cisplatin was recommended. Cisplatin (80 mg/m2) was infused intravenously within 30 min on day 1, and 5-fluorouracil (800 mg/m2) was infused continuously on days 1-5 of a 28-day cycle. Thrombocytopenia (grade 3) occurred on day 16, leucopenia (grade 3) occurred on day 23, and anemia (grade 3) occurred on day 30. The onset of hematologic toxicities was prolonged in comparison to patients with a normal renal function.

Are additional trace elements necessary in total parenteral nutrition for patients with esophageal cancer receiving cisplatin-based chemotherapy?

It is known that cisplatin induces the excretion of zinc from the urine and thereby reduces its serum concentration. However, the fluctuation of these trace elements during or after cisplatin-based chemotherapy has not been evaluated. To answer this question, we performed a clinical study in esophageal cancer patients undergoing cisplatin-based chemotherapy. Eighteen patients with esophageal cancer who were not able to swallow food or water orally due to complete stenosis of the esophagus were evaluated. The patients were divided into a control group [total parenteral nutrition (TPN) alone for 28 days, ten cases] and an intervention group (TPN with additional trace elements for 28 days, eight cases). The serum concentrations of zinc, iron, copper, manganese, triiodothyronin (T3), and thyroxin (T4), as alternative indicators of iodine, were measured on days 0, 14, and 28 of treatment, and statistically analyzed on day 28. In the control group, the serum concentration of copper was significantly decreased from 135.4 (day 0) to 122.1 µg/ml (day 14), and finally to 110.6 µg/ml (day 28, p = 0.015). The concentration of manganese was also significantly decreased from 1.34 (day 0) to 1.17 µg/ml (day 14) and finally to 1.20 (day 28, p = 0.049). The levels of zinc, iron, T3, and T4 were not significantly changed. In the intervention group, the supplementation with trace elements successfully prevented these decreases in their concentrations. TPN with supplementary trace elements is preferable and recommended for patients who are undergoing chemotherapy in order to maintain the patients' nutrient homeostasis.

Possible involvement of antitumor immunity in the eradication of colon 26 induced by low-voltage electrochemotherapy with bleomycin.

PURPOSE: The antitumor efficiency of electrochemotherapy using chemotherapeutic agents and high-voltage electric pulse has been reported. This study was done to define the precise nature of the involvement of antitumor immunity in the regression of tumor nodules in electrochemotherapy, and to evaluate the effectiveness of using low-voltage electroporation. METHODS: Balb/c mice and Balb/c nu/nu nude mice were inoculated subcutaneously with Colon 26 cells or Meth A cells. Electrochemotherapy using bleomycin and low-voltage electroporation (CUY21) was performed as a treatment against tumor nodules. RESULTS: Colon 26 tumors were eradicated in the mice given an intratumor (i.t.) injection of 500 microg bleomycin followed by treatment with electric fields ranging from 50 to 150 V/cm, with complete response rates ranging from 80% to 100%. The mice rejected inoculations of rechallenged Colon 26 cells, but not Meth A cells. In the Balb/c nu/nu nude mice, complete regression of the tumor was not seen after electrochemotherapy under the same therapeutic conditions that resulted in almost complete cure in the Balb/c mice. CONCLUSION: Our results suggest that the generation of T-cell-dependent, tumor-specific protective immunity might be involved in the process of tumor nodule regression in low-voltage electrochemotherapy.