Pharmacodynamic Study of the Saltz Regimen for Metastatic Colorectal Cancer in a Hemodialyzed Patient

Abstract

Objective: Combination therapy with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin is widely used for the treatment of metastatic colorectal cancer. However, little is known about the safety of chemotherapy of malignancies in hemodialysis (HD) patients. We encountered a patient with colorectal carcinoma on HD. We decided to administer combination chemotherapy while monitoring the pharmacodynamics of the patient. Case Report: A 74-year-old male received regular HD 3 times a week because of type 1 diabetes mellitus. He was diagnosed with stage IV colorectal cancer in November 2004. After sigmoidectomy, the patient received chemotherapy: a weekly schedule of CPT-11 (50 mg/m²) was administered followed by l-leucovorin (10 mg/m²) and 5-FU (400 mg/m²) just after HD. During the course, the plasma concentrations of both SN-38, an active metabolite of CPT-11, and 5-FU were not increased compared with those of patients with normal renal function. Our patient presented with grade III hematological toxicity that was easily recovered by granulocyte colony-stimulating factor. Conclusion: These data suggest that the dose-reduced Saltz regimen can be feasible for colorectal cancer patients receiving dialysis as postoperative adjuvant chemotherapy.

Irinotecan in Cancer Patients with End-Stage Renal Failure

“…A review of published case reports of irinotecan in patients with ESRF indicates that weekly doses of 50-80 rng/m' were generally tolerated, whereaseven single doses of more than 125 mg/m' were associated with serious adverse events (Table3). [26][27][28] Taken together, our results indicate an increased exposure to SN-38 in patients with ESRF, which might explain the increased risk of adverseevents as described in case reports. However, since our patient was not genotyped, the presenceof a polymorphism leading to the observedpharmacokinetics independently from renal function cannot be excluded.Furthermore,even in patients with normal renal function, both grade III or IV diarrhea and grade III or IV neutropenia were observedin 31% of cases," In addition, a publication bias regarding previouscase reports cannot be excluded We concludethat reduced-dose irinotecan administered weekly for3 weeks followed by a pauseof 1weekisfeasible in the palliative therapy of metastatic colorectal cancerin patients withESRF.…”

Safety of Regular-Dose Imatinib Therapy in Patients with Gastrointestinal Stromal Tumors Undergoing Dialysis

“…Dialysis patients with esophageal cancer have been administered 5-fluorouracil and cisplatin [ 7 , 8 , 9 ] and dialysis patients with gastric cancer have been administered tegafur-uracil, docetaxel, and irinotecan [ 10 , 13 ]. Dialysis patients with colon cancer have been treated with tegafur-uracil, irinotecan, and oxaliplatin [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. In these cases, most cytotoxic drugs were used safely without dose modification, but irinotecan caused severe myelosuppression and resulted in death [ 15 , 18 ].…”

Concurrence of UGT1A Polymorphism and End-Stage Renal Disease Leads to Severe Toxicities of Irinotecan in a Patient with Metastatic Colon Cancer

“…Uremia and poor dialyzability of SN-38 may be partial causes leading to delayed clearance and higher AUC 0-∞ of SN-38, which then is an important factor responsible for the severe toxicity in our patient. As shown in Table 3, which includes all the reports using irinotecan in cancer patients undergoing hemodialysis searched from PubMed 5,12,[15][16][17][19][20][21][22] , 5 of 6 reports showed accumulation of SN-38 in hemodialysis patients receiving irinotecan. Of the 10 reports regarding irinotecan usage in hemodialysis patients, 3 reported good tolerance, 3 reported grade 3 neutropenia, and 4 reported severe adverse effects (grade 4 or higher toxicities).…”