Metronomic Outpatient-Based Chemotherapy with 5′-DFUR and Low-Dose Cisplatin for Conventional Platinum-Based Chemotherapy-Resistant Advanced Urothelial Cancer

• Main Authors: Tomohiko Hara, Satoru Yoshihiro, Hideaki Ito, Kazuhiro Nagao, Chietaka Ohmi, Shigeru Sakano, Hideyasu Matsuyama, Katsusuke Naito
• Format: Article
• Language: English
• Published: SAGE Publishing 2007-01-01
• Series: Clinical Medicine Insights: Oncology
• Online Access: https://doi.org/10.4137/CMO.S304

Background Metronomic chemotherapy is aimed at lessening the adverse effects of treatment while rendering cancer cells cytostatic. The oral 5-fluorouracil prodrug “5′-DFUR” has been shown to inhibit angiogenesis and is regarded as a good candidate agent for metronomic chemotherapy. Moreover, cisplatin and 5′-DFUR have been shown to synergistic cytotoxic effects. Methods We evaluated the safety and efficacy of metronomic chemotherapy using daily oral 5′-DFUR at the dose of 600 mg/day and biweekly cisplatin infusion at the dose of 20 mg/person in 23 patients with urothelial cancer resistant to conventional platinum-based chemotherapy. Results Twenty-three patients were enrolled between August 2000 and December 2004. The median survival time after the initiation of metronomic chemotherapy was 15.2 months. The 1-year, 2-year and 3-year survival rates were 55.1%, 45.1% and 5.9%, respectively. Grade 3 fatigue was observed as severe toxicity in one patient. No cases showed nephrotoxicity and adverse effects necessitating medical intervention. Conclusions Although a large-scale prospective study would be necessary before the therapy is established as a standard, our metronomic chemotherapy regimen appears to be a potentially useful palliative treatment alternative for patients with advanced urothelial cancer resistant to conventional platinum-based chemotherapy. Abbreviations M-VAC: methotrexate, vinblastine, doxorubicin, and cisplatin; GC: gemcitabine and carboplatin; 5′-DFUR: 5′-deoxy-5-fluorouridine; 5-FU: 5-fluorouracil; CDDP: cisplatin; TCC: transitional cell carcinoma; ECOG: Eastern Cooperative Oncology Group; PS: performance status; UICC: Union International Contre le Cancer; WHO: World Health Organization; NCI-CTC: National Cancer Institute Common Toxicity Criteria; CI: confidence interval; PR: partial response; NC: no change; PD: progressive disease; TP: thymidine phosphorylase; AUC: areas under the curve.