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Use of KW-2189, a DNA minor groove-binding agent, in patients with hepatocellular carcinoma: a north central cancer treatment group (NCCTG) phase II clinical trial.

AbstractBACKGROUND:
Hepatocellular carcinoma (HCC) is a common cancer in certain portions of the world. Currently no effective therapies exist for patients with advanced or metastatic HCC. KW-2189, a DNA minor groove-binding agent, has shown promising activity against HCC in preclinical evaluations.
METHODS:
A phase II study was conducted to evaluate the activity of KW-2189 in patients with histologic or cytologic confirmed advanced or metastatic HCC who had no prior systemic therapy. Patients received KW-2189 at a dose of 0.5 mg/m2 administered on day 1 of a 6-week cycle. The primary endpoint of the trial was objective regression. Other endpoints included toxicity, disease-free survival, and overall survival.
RESULTS:
Due to hematologic toxicity the dose of KW-2189 was reduced to 0.375 mg/m2 after 11 patients had been enrolled into the trial. Due to continued significant hematologic toxicity in the next five patients enrolled at the lower dose the trial was closed to accrual. Two responses were seen in patients enrolled at the higher dose, including one sustained CR.
CONCLUSION:
KW-2189 showed evidence of anti-tumor activity in HCC. However, because of significant and prolonged hematologic toxicity, when given as a single dose every 6 weeks, further development of this drug in HCC is not possible. Further exploration of DNA minor groove-binding agents in the treatment of HCC appears warranted.
AuthorsSteven R Alberts, Vera J Suman, Henry C Pitot, John K Camoriano, Joseph Rubin
JournalJournal of gastrointestinal cancer (J Gastrointest Cancer) Vol. 38 Issue 1 Pg. 10-4 ( 2007) ISSN: 1941-6628 [Print] United States
PMID19065716 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antineoplastic Agents
  • Duocarmycins
  • Pyrrolidinones
  • KW 2189
Topics
  • Adult
  • Aged
  • Antineoplastic Agents (administration & dosage, adverse effects)
  • Carcinoma, Hepatocellular (drug therapy, mortality)
  • Duocarmycins
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms (drug therapy, mortality)
  • Male
  • Middle Aged
  • Pyrrolidinones (administration & dosage, adverse effects)
  • Treatment Outcome

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