A phase II pilot study of KW-2189 in patients with advanced renal cell carcinoma.
BACKGROUND
KW-2189 is a semi-synthetic, water-soluble analog of duocarmycin B2, a new class of potent antitumor antibiotics produced by streptomyces, with improved in vitro antitumor potency.


METHODS
Forty patients with pathologically confirmed metastatic renal cell carcinoma were treated in this multicenter, open-label phase II trial. All patients received 0.4 mg/m2 KW-2189 as an i.v. infusion for Cycle I. Cycles were repeated every 5 to 6 weeks with escalations to 0.5 mg/m2 in the absence of significant toxicity or disease progression.


RESULTS
No patient had an objective response. The most common drug-related toxicity was hematological-delayed neutropenia and thrombocytopenia, with recovery by week 6. Non-hematologic toxicity consisted of mild to moderate fatigue, nausea and vomiting, and anorexia that was generally manageable.


CONCLUSIONS
KW-2189 in this dose and schedule has a predictable safety profile of reversible myelosuppression. No activity in metastatic renal cell carcinoma was demonstrated.
Small
E J
EJ
UCSF Comprehensive Cancer Center, University of California, San Francisco 94115, USA. smalle@medicine.ucsf.edu
Figlin
R
R
Petrylak
D
D
Vaughn
D J
DJ
Sartor
O
O
Horak
I
I
Pincus
R
R
Kremer
A
A
Bowden
C
C
D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D000080890:Duocarmycins; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D000080890:Duocarmycins; D011760:Pyrrolidinones; C086920:KW 2189