A phase II trial of weekly i.v. KW-2170 in advanced castrate-resistant prostate cancer

Asia Pac J Clin Oncol. 2010 Dec;6(4):292-7. doi: 10.1111/j.1743-7563.2010.01328.x. Epub 2010 Nov 3.

Abstract

Aim: KW-2170 is a novel pyrazoloacridone derivative that intercalates nucleic acids. It has promising in vitro properties against prostate and other cancers and is active in vivo against doxorubicin-resistant cell lines. We wished to investigate its activity and toxicity profile in this Phase II trial in androgen independent prostate cancer.

Methods: Overall 44 men were recruited to this multicenter, open label, non-randomized study, with 35 evaluable for prostatic specific antigen (PSA) response.

Results: Five patients had a PSA fall greater than 50% (overall RR 14.3%, 95% CI 4.8-30.3%). Overall median survival was 16 months. In the evaluable group (n = 35), median survival was 18.9 months. The drug was very well tolerated, with the most common toxicities being hematological (anemia, leucopenia, thrombocytopenia), alopecia, fatigue, and nausea. However, most of these were National Cancer Institute Grade 1 or 2; Grade 3 neutropenia occurred in only 11% of patients, and there was no Grade 4 neutropenia. Quality of life as measured by the FACT-P scale was not compromised.

Conclusion: KW-2170 is a very well tolerated chemotherapy agent. It has a relatively low PSA response rate, and did not meet the pre-specified criteria for further studies.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Acridines / therapeutic use*
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Castration
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / pathology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Pyrazoles / therapeutic use*
  • Quality of Life
  • Survival Rate
  • Treatment Outcome

Substances

  • Acridines
  • Antineoplastic Agents
  • Pyrazoles
  • KW 2170