Related Experiment Videos
Phase II study of sulofenur (LY 186641). A novel antineoplastic agent in advanced non-small cell lung cancer
N C Munshi1, D E Seitz, F Fossella
1Indiana University School of Medicine, Indianapolis.
Abstract:
Sulofenur is a member of a new class of antineoplastic agents with a novel chemical structure and unique pharmacological and biological properties. Preclinical studies have demonstrated a wide spectrum of anti-tumor activity against murine solid tumors and human tumor xenografts. In phase I trials, only mild toxicities were observed. Twenty-six patients (pts), two of whom were inevaluable, with advanced non small cell lung cancer without prior chemotherapy were entered on this phase II trial. Pts received 800 mg/m2 sulofenur po Monday-Friday x 21 days, q 28 days. Seventeen male and 9 female pts with median performance status 1 received a median of 2 courses. Twenty pts had stage IV disease and 19 pts had adenocarcinoma, 6 squamous cell and 1 undifferentiated carcinoma. The main toxicity was grade 1 to 3 anemia in 16 (62%) pts, with hemolysis noted in 9 pts. Although methemoglobinemia was observed in 19 pts, it was severe in only 3 pts. Transient elevation of alkaline phosphatase was seen in 11 pts and one pt had a minor abnormality in glucose metabolism. Other common chemotherapy related side effects such as granulocytopenia or alopecia were not encountered with this agent. Of 24 evaluable pts, two pts had stable disease or minor response and 22 pts had progressive disease. In conclusion although sulofenur had only minor side effects, in the dosage and schedule used, it did not produce any significant response in advanced non-small cell lung cancer.
Insights
Sulofenur, a novel antineoplastic agent, showed minimal toxicity in advanced non-small cell lung cancer patients. However, the study found no significant anti-tumor response with the tested dosage and schedule.
Area of Science:
- Oncology
- Pharmacology
- Drug Development
Background:
- Sulofenur represents a new class of antineoplastic agents with unique properties.
- Preclinical studies indicated broad anti-tumor activity in various cancer models.
- Phase I trials suggested a favorable safety profile with mild toxicities.
Purpose of the Study:
- To evaluate the efficacy and safety of sulofenur in patients with advanced non-small cell lung cancer (NSCLC).
- To determine the anti-tumor activity of sulofenur in a Phase II clinical trial setting.
Main Methods:
- A Phase II trial was conducted on 26 patients with advanced NSCLC who had not received prior chemotherapy.
- Patients received sulofenur at a dose of 800 mg/m2 orally, Monday-Friday for 21 days every 28 days.
- Toxicity, response, and disease progression were monitored in evaluable patients.
Main Results:
- The primary toxicity observed was grade 1-3 anemia (62%), with hemolysis in 9 patients and methemoglobinemia in 19 patients (severe in 3).
- Transient elevations in alkaline phosphatase and minor glucose metabolism abnormalities were noted.
- Among 24 evaluable patients, only 2 showed stable disease or minor response, while 22 experienced progressive disease.
Conclusions:
- Sulofenur demonstrated a manageable toxicity profile with mild side effects in advanced NSCLC patients.
- The tested dosage and schedule of sulofenur did not yield significant anti-tumor responses in this patient population.
- Further investigation into different dosages or schedules may be warranted, but current findings suggest limited efficacy for advanced NSCLC.