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. PATIENTS AND 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.
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. PATIENTS AND 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.
Authors: G F Fleming; M J Ratain; S M O'Brien; R L Schilsky; P C Hoffman; J M Richards; N J Vogelzang; D A Kasunic; R H Earhart Journal: J Natl Cancer Inst Date: 1994-03-02 Impact factor: 13.506
Authors: E Kobayashi; A Okamoto; M Asada; M Okabe; S Nagamura; A Asai; H Saito; K Gomi; T Hirata Journal: Cancer Res Date: 1994-05-01 Impact factor: 12.701
Authors: K Gomi; E Kobayashi; K Miyoshi; T Ashizawa; A Okamoto; T Ogawa; S Katsumata; A Mihara; M Okabe; T Hirata Journal: Jpn J Cancer Res Date: 1992-01
Authors: H Ogasawara; K Nishio; Y Takeda; T Ohmori; N Kubota; Y Funayama; T Ohira; Y Kuraishi; Y Isogai; N Saijo Journal: Jpn J Cancer Res Date: 1994-04