An early phase II trial of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma.
OBJECTIVE
S-1, an oral anticancer agent, contains tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1. The aim of this trial was to investigate the efficacy and safety of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma (RCC).


METHODS
We conducted a non-randomized, open-label trial in Japanese patients with metastatic RCC who had received nephrectomy and had failed cytokine-based immunotherapy. The primary endpoint was response rate. S-1 40-60 mg based on the body surface area was administered twice daily (80-120 mg/day) for 4 consecutive weeks, followed by a 2-week rest period; cycles were repeated every 6 weeks. Patients continued treatment until disease progression, unacceptable toxicity, or withdrawal of consent.


RESULTS
A total of 20 eligible patients were enrolled. Among these, 3 patients had partial response, yielding objective response rate of 15%; 13 patients had no change; 4 patients had progressive disease. The median time-to-progression and median overall survival were 12.0 and 25.7 months, respectively. The initial adverse event was generally mild to moderate in severity. The most common grade 3/4 drug-related hematological and non-hematological adverse events were neutropenia (20.0%) and anorexia (20.0%), respectively.


CONCLUSIONS
S-1 is active and well tolerated for the treatment of cytokine-refractory metastatic RCC.
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. naito@uro.med.kyushu-u.ac.jp
Seiji
S
Naito
Taiji
T
Tsukamoto
Michiyuki
M
Usami
Hiroyuki
H
Fujimoto
Hideyuki
H
Akaza
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D016207:Cytokines / Q000627:therapeutic use*; D018450:Disease Progression; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D007564:Japan; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; D004338:Drug Combinations; D007376:Interleukin-2; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D007372:Interferons