Tamoxifen and colchicine-modulated vinblastine followed by 5-fluorouracil in advanced renal cell carcinoma: a phase II study.
OBJECTIVE
Chemotherapy resistance of renal cell carcinoma (RCC) has been attributed in large part to multidrug resistance (MDR). Reported MDR-modulated chemotherapy for RCC, however, has resulted in only marginal response benefits. In this study, the MDR-modulated effect of paired tamoxifen and colchicine on vinblastine and the possible additive effect of 5-fluorouracil (5-FU) were investigated in the treatment of advanced RCC.


METHODS
Chemotherapy was administered every 4 weeks with biweekly vinblastine (4 mg/m(2)/day, intravenously on days 1 and 15) modulated by oral tamoxifen (100 mg/day) and colchicine (1 mg/day) from days -1 to 2 and from days 13 to 16. 5-FU (800 mg/m(2)/day from days 2 to 5) was administered after vinblastine administration as a continuous infusion.


RESULTS
Of 17 eligible patients with advanced RCC available for evaluation, 1 achieved a complete response (CR) and 3 a partial response (PR), with an overall response (CR plus PR) rate of 23.5%. The median overall survival time of all patients was 10 months (95% confidence interval [CI] 3.5 to 16.5); that of our patients with poor, intermediate, and favorable risks as stratified by Motzer's model was 6 (95% CI 1.7 to 10.3), 10 (95% CI 7.9 to 12.2), and 26 (95% CI 24.4 to 27.6) months, respectively. These results are encouraging in view of the poor efficacy of chemotherapy in RCC observed previously. Additionally, the treatment toxicity was limited: toxicity of grade 3 or greater occurred in only 1 patient with leukopenia, and no treatment-related mortality was found.


CONCLUSIONS
The encouraging response rates and overall survival with limited toxicity warrant further investigation of this combination therapy as an integrated part of immunochemotherapy for RCC.
Liu
J H
JH
Division of Medical Oncology, Taipei Veterans General Hospital and National Yang-Ming University, Republic of China, Taipei, Taiwan.
Yang
M H
MH
Fan
F S
FS
Yen
C C
CC
Wang
W S
WS
Chang
Y H
YH
Chen
K K
KK
Chen
P M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D003078:Colchicine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013629:Tamoxifen / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage
D013629:Tamoxifen; D014747:Vinblastine; D003078:Colchicine; D005472:Fluorouracil