Feasibility of pre- and postoperative gemcitabine-plus-cisplatin systemic chemotherapy for the treatment of locally advanced urothelial carcinoma in kidney transplant patients

Objective: To investigate the feasibility of pre- and postoperative gemcitabine-plus-cisplatin (GC) adjuvant chemotherapy for the treatment of locally advanced urothelial carcinoma in kidney transplant patients.

Methods: Seven kidney transplant patients diagnosed with locally advanced urothelial carcinoma were treated with a pre- and postoperative GC adjuvant chemotherapy between January 2008 and March 2012. Gemcitabine (800 mg/m(2)) was administered at as an intravenous infusion on days 1 and 8. A total cisplatin dosage of 100 mg/cycle was administered on 2 days (50 mg/d on days 2 and 3) as an intravenous infusion. A single treatment cycle lasted 21 days. At the beginning of chemotherapy, the cyclosporine (CSA) dosage was reduced by 25 mg/d (on day 1 through day 8) if the blood CSA concentration was well maintained and did not fluctuate significantly. In addition, mycophenolate mofetil was reduced by 500 mg/d, while azathioprine was reduced by 25 mg/d (on day 1 through day 16). One cycle of GC neoadjuvant chemotherapy was given before operation, and several GC cycles were given after operation according to the patients' situation. Retrospective analysis was performed on the clinical data, chemotherapy regimen, chemotherapy efficacy, and side effects of the 7 patients.

Results: The 7 patients were all treated with 1 course of presurgical chemotherapy. The seven patients completed 24 treatment cycles of chemotherapy in total. The average GC medication period per patient was 3.4 cycles. The postsurgery follow-up was 6 to 36 months (average-22.1); all of the patients survived. There was 1 case of complete remission (14.5%), 2 of partial remission (28.5%), and 4 of stable disease (57%), with one case of T4N1M0 and three cases of T3N0M0. The overall efficacy was 43%. The toxicity and side effects associated with the GC regimen were largely associated with myelosuppression. The other side effects included reversible nephrotoxicity, gastrointestinal tract and skin reactions, as well as phlebitis. Hematologic toxic reactions included reversible leukopenia, thrombocytopenia, and anemia. There was 1 case of degree III anemia and 1 case of degree II; 5 cases of degree III and 1 of degree II leukopenia; and 3 of degree II thrombocytopenia. Gastrointestinal reactions included nausea, vomiting, and constipation. There were 2 cases of degree III and 4 cases of degree II nausea and vomiting as well as 2 cases of degree III and 3 cases of degree II constipation. There were 3 cases of degree I phlebitis (43%) and 2 cases of degree I skin erythema. The nephrotoxicity reactions were all reversible. Both liver function and grafted kidney function were not significantly altered after chemotherapy compared with prior to chemotherapy. None of the patients suffered renal allograft rejection after chemotherapy; none required additional antirejection drug treatments. The original antirejection treatment regimen was restored after the patients completed the chemotherapy treatment cycles.

Conclusion: We confirmed the efficacy of applying a GC regimen to treat locally advanced urothelial carcinoma in kidney transplant patients. The side effects were tolerable and reversible with minor impacts on graft function.