Phase-II trial of combination treatment of interferon-α, cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin-system inhibitor (I-CCA therapy) for advanced renal cell carcinoma.
We have recently reported favorable responses to a combination treatment comprising cimetidine, a cyclooxygenase-2 inhibitor and a renin-angiotensin-system inhibitor in metastatic renal cell carcinoma (RCC). In view of the potential synergistic effects of these three agents and interferon-α (I-CCA therapy), we conducted a phase-II trial to examine the efficacy and toxicity of I-CCA as first-line treatment. Fifty-one patients with advanced RCC received natural interferon-α (3-6 million U thrice/week) and cimetidine (800 mg), cyclooxygenase-2 inhibitor meloxicam (10 mg), and renin-angiotensin-system inhibitor candesartan (4 mg) or perindopril (4 mg) orally daily. Memorial Sloan-Kettering Cancer Center prognostic categories were favorable, intermediate and poor in 10 (20%), 31 (61%) and 10 (20%) patients, respectively. The primary end-point was the objective response rate (ORR) and the secondary end-points included clinical benefit, progression-free survival (PFS), overall survival (OS) and safety. Median follow-up was 19 months. Complete response (CR) was observed in four patients (8%) and partial response in seven (14%), yielding an ORR of 22%. None of the four patients who achieved CR relapsed during the 16- to 81-month follow up. The ORR were 17% in the favorable- or intermediate-risk group and 40% in the poor-risk group. The other 24 patients (45%) had stable disease for at least 6 months, resulting in a clinical benefit rate of 67%. The median PFS and OS were 12 and 30 months, respectively. Grade 3/4 toxicities were never observed. The I-CCA therapy, providing favorable responses and low toxicity profiles, is worthy of further consideration as a first-line therapy for metastatic RCC.
Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Manabu
M
Tatokoro
Yasuhisa
Y
Fujii
Satoru
S
Kawakami
Kazutaka
K
Saito
Fumitaka
F
Koga
Yoh
Y
Matsuoka
Yasumasa
Y
Iimura
Hitoshi
H
Masuda
Kazunori
K
Kihara
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D002927:Cimetidine / Q000008:administration & dosage; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage; D013777:Tetrazoles / Q000008:administration & dosage
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D052246:Cyclooxygenase 2 Inhibitors; D016898:Interferon-alpha; D013777:Tetrazoles; D002927:Cimetidine; C081643:candesartan; D020913:Perindopril