Neovastat (AE-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels.
BACKGROUND
renal cell carcinoma (RCC) is a potential target for anti-angiogenic drugs because of its high vascularization. Neovastat (AE-941) is an inhibitor of angiogenesis with a mechanism of action that could prove beneficial in the treatment of RCC. Patients and design A phase II trial was conducted to identify the long-term safety profile of Neovastat in advanced cancer patients and to obtain preliminary information on its efficacy in solid tumors refractory to standard treatments. Neovastat (60 or 240 ml/day) was administered orally (b.i.d.) to 144 patients with solid tumors refractory to standard therapies or for whom no standard treatments were available.


RESULTS
A survival analysis was conducted on 22 patients with a primary diagnosis of refractory RCC to determine whether the dose of Neovastat had any effect. A significant relationship between dose and survival was observed; the median survival time was significantly longer (16.3 versus 7.1 months; P = 0.01) in patients treated with Neovastat 240 ml/day (n = 14) compared with patients receiving 60 ml/day (n = 8). No dose-limiting toxicity was reported. The most frequent adverse event was taste alteration (13.6%).


CONCLUSIONS
Neovastat is well tolerated by advanced cancer patients at doses of 60 and 240 ml/day. The higher dose of Neovastat administered in this trial is associated with a survival benefit in RCC, which is not explained by differences in major prognostic factors.
Batist
G
G
McGill Center for Translational Research in Cancer, McGill University, Montréal, Quebec, Canada. gbatist@onc.jgh.mcgill.ca
Patenaude
F
F
Champagne
P
P
Croteau
D
D
Levinton
C
C
Hariton
C
C
Escudier
B
B
Dupont
E
E
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002356:Cartilage / Q000737:chemistry; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012754:Sharks; D015996:Survival Rate; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D014020:Tissue Extracts; C111481:shark cartilage extract