Efficacy and toxicity of the novel chemotherapeutic agent KW-2170 in recurrent epithelial ovarian cancer.

Abstract

OBJECTIVES:

KW-2170 is a novel DNA intercalating agent whose mechanism of action is similar to doxorubicin HCl, yet is associated with less cardiac toxicity. The objective of this study was to evaluate the activity and toxicity of this novel chemotherapeutic agent in patients with recurrent ovarian carcinoma.

METHODS:

A prospective phase II trial was performed in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma and measurable disease. Patients could have platinum-sensitive or refractory disease and could have received any number of prior treatments. One treatment cycle consisted of KW-2170 administered at a dose of 18 mg/m(2) weekly for 3 weeks followed by a 21-day rest period. Toxicity was assessed using the NCI Common Toxicity Criteria (Version 2.0), and dose reduction was allowed for significant toxicity. Response to therapy was assessed in patients who completed at least 2 cycles using RECIST criteria.

RESULTS:

A total of 28 patients were enrolled in this phase II trial at 5 separate centers. Of the 28 patients evaluated, all had stage III/IV disease at initial diagnosis. The median number of prior therapeutic regimens in these patients was 4 (range 1-8). The median number of KW-2170 cycles administered was 2 (range 1-5). Treatment-related toxicity in this heavily pretreated population was acceptable as only 6 patients (21%) had grade 3-4 neutropenia. Dose reductions occurred in 6 patients (21%) for grades 1-4 neutropenia, and no patient had febrile neutropenia. Four patients completed less than 1 cycle; 3 secondary to progressive disease, and one due to Gram-positive sepsis. Of patients receiving at least 2 full cycles, 10 patients (55%) had stable disease with a median of 4.5 months (range 3-10) to disease progression. All other patients were removed from the study after 1-2 cycles of therapy with no significant clinical effect noted.

CONCLUSIONS:

Although associated with relatively little toxicity, KW-2170 at the dose and schedule evaluated demonstrated little clinical activity in this heavily pretreated population of recurrent ovarian cancer patients. Whether KW-2170 would have greater clinical activity in a more treatment naive group of patients at an increased dose awaits clinical trial evaluation.

• Authors: Jacob M Estes, Charles A Leath, Sybilann Williams, Manuel R Modiano, Michael Sawyer, David Cohn, J Michael Straughn, Mack N Barnes, Ronald D Alvarez
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 102 Issue 2 Pg. 338-42 (Aug 2006) ISSN: 0090-8258 [Print] United States
• PMID: 16487997 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Acridines
• Antineoplastic Agents
• Pyrazoles
• KW 2170

Topics

• Acridines (adverse effects, therapeutic use)
• Adult
• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• Female
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Ovarian Neoplasms (drug therapy)
• Prospective Studies
• Pyrazoles (adverse effects, therapeutic use)