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Phase I evaluation of an epothilone B analog (BMS-247550): clinical findings and molecular correlates

Li Liu, MD

University of Pennsylvania Cancer
Last Modified: May 13, 2001

Presenter: S. Mani
Affiliation: NYU Medical Center, NY

Background:

The epothilones are naturally occurring antimitotic drugs that share with the taxanes a similar mechanism of action without apparent structural similarity. Some early pre-clinical data demonstrated activity against taxane- sensitive and -resistant tumors,

Materials and Methods:

• A total of 13 patients with various solid malignancies were included in this phase I study
• Patients were treated with 1-hour infusion of BMS-247550 once every 3 weeks
• Five dose levels ranging from 7.4 mg/m2 to 59.2 mg/m2 were evaluated

Results:

• At dose of 50mg/m2, 50% of patients experienced dose-limiting neutropenia/sepsis
• Other toxicity include neuropathy, anorexia, and weakness
• Three patients had subjective responses

Authors' Conclusions

• The MTD of BMS-247550 was established in this phase I study
• Clinical response was seen one patient with taxane-refractory breast cancer

Clinical/Scientific Implications:

• The premominant dose-limiting toxicity of BMS- 247550 is neutropenia
• Clinical toxicity profile should be validated in large trials
• The clinical responsiveness will be assessed in phase II trials