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Phase II study of dolastatin-10 as first-line treatment for advanced colorectal cancer
Everardo D Saad1, Eric H Kraut, Paulo M Hoff
1Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:
Dolastatin-10 is a potent inhibitor of microtubule assembly derived from the sea hare, which displayed significant antitumor activity in preclinical models. We conducted a phase II study of dolastatin-10 in patients with advanced colorectal cancer and no prior chemotherapy for metastatic disease. Fourteen patients received doses ranging from 300 microg/m(2) to 450 microg/m(2) as an intravenous push every 21 days. There were no major objective responses. Toxicity was mainly hematologic, with grade III or IV granulocytopenia occurring in 9 of 42 treatment courses. Other toxic effects were generally mild. Dolastatin-10 lacks clinically significant activity in advanced colorectal cancer when used in this dose and schedule.
Insights
Dolastatin-10 showed no significant antitumor activity in advanced colorectal cancer patients. The drug primarily caused hematologic toxicity, specifically granulocytopenia, limiting its clinical utility.
Area of Science:
- Oncology
- Pharmacology
Background:
- Dolastatin-10, a potent microtubule assembly inhibitor from sea hares, demonstrated preclinical antitumor efficacy.
- Advanced colorectal cancer remains a significant clinical challenge with unmet treatment needs.
Purpose of the Study:
- To evaluate the clinical activity and toxicity of Dolastatin-10 in patients with advanced colorectal cancer.
- To determine the optimal dose and schedule for Dolastatin-10 in this patient population.
Main Methods:
- A Phase II clinical trial was conducted.
- Fourteen patients with advanced colorectal cancer received intravenous Dolastatin-10 at doses from 300 to 450 microg/m(2) every 21 days.
- Objective response and toxicity were assessed.
Main Results:
- No major objective responses were observed in any patient.
- Hematologic toxicity, particularly grade III or IV granulocytopenia, occurred in 9 of 42 treatment courses.
- Other reported toxicities were generally mild.
Conclusions:
- Dolastatin-10 demonstrated a lack of clinically significant activity in advanced colorectal cancer.
- The observed toxicity profile, mainly hematologic, suggests limitations for this drug at the tested dose and schedule.
