Vinblastine and estramustine phosphate in metastatic renal cell carcinoma: a phase II trial of the Fox Chase Network.
BACKGROUND
It is well known that metastatic renal cell carcinoma (RCC) exhibits constitutive resistance to chemotherapeutic agents. Antimicrotubule agents such as vinblastine are associated with low but reproducible response rates (approximately 12%) in patients with RCC. Estramustine has been shown to potentiate the antimicrotubule effects of vinblastine. The authors sought to increase the activity of vinblastine in RCC through the addition of estramustine.


METHODS
Twenty-one patients with metastatic RCC not previously treated with chemotherapy received oral estramustine phosphate, 600 mg/m(2), on Days 1, 2, and 3 weekly for 6 weeks, and intravenous vinblastine, 4 mg/m(2) on Day 2 weekly for 6 weeks, repeated every 8 weeks. Twenty-one patients received 31 cycles of therapy.


RESULTS
Two patients experienced Grade 3 and 4 hematologic toxicity, and three patients had Grade 3 nonhematologic toxicity consisting of neurologic toxicity, hepatic toxicity, or angioneurotic edema. One patient had a partial response with decreased liver metastases for 48 weeks; 9 patients had stable disease, for a median duration of 14 weeks (range, 11-31 weeks); and 11 patients demonstrated disease progression. The median overall time to progression was 8 weeks and the median overall survival period was 24 weeks.


CONCLUSIONS
Although well tolerated, the combination of oral estramustine phosphate with vinblastine administered on this schedule had minimal activity in patients with metastatic RCC.
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. nb_haas@fccc.edu
Naomi B
NB
Haas
Bruce J
BJ
Giantonio
Samuel
S
Litwin
Carl J
CJ
Minniti
Stephen
S
Fox
Gwen
G
Yeslow
Robert
R
Reilly
Kenneth
K
Nahum
Richard
R
Greenberg
Theresa
T
Halbherr
Gary R
GR
Hudes
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004961:Estramustine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage* / Q000009:adverse effects
D004961:Estramustine; D014747:Vinblastine