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Phase II trial of ICRF-187 in children with solid tumors and acute leukemia
T Vats1, B Kamen, J P Krischer
1University of Kansas Medical School, Kansas City.
Insights
The novel drug ICRF-187, a more water-soluble form of razoxane, showed limited efficacy in treating solid tumors and leukemia in children. While generally well-tolerated, it did not produce objective responses in this phase II trial.
Area of Science:
- Pediatric Oncology
- Pharmacology
- Clinical Trials
Background:
- ICRF-187 is the (+) enantiomer of razoxane (ICRF-159), offering improved water solubility for parenteral administration.
- Previous Phase I trials established a maximum tolerated dose of 3500 mg/M2/day for 3 days in pediatric patients.
Purpose of the Study:
- To evaluate the efficacy and safety of ICRF-187 in pediatric patients with solid tumors and acute leukemia.
- To assess response rates and toxicity profiles in a pediatric population.
Main Methods:
- A Phase II clinical trial involving 21 children with solid tumors and 35 with acute leukemia (all under 21 years old).
- Patients had recovered from prior chemotherapy, with normal organ function and a prognosis >4 weeks.
- ICRF-187 was administered at 3 g/M2/day for 3 days via a 4-hour infusion daily.
Main Results:
- No objective bone marrow responses were observed in leukemia patients, though some showed decreased peripheral blast counts.
- No measurable responses were detected in pediatric patients with solid tumors.
- ICRF-187 was well-tolerated, with hematopoietic depression as the primary toxicity. Nausea, vomiting, and elevated liver enzymes were rare but significant side effects.
Conclusions:
- ICRF-187 demonstrated limited efficacy in the evaluated pediatric patient groups under the tested regimen.
- The drug was generally well-tolerated, with manageable toxicities.
- Further investigation into alternative dosing schedules may be warranted to explore potential activity.
Abstract:
ICRF-187 is the (+) enantiomer of the racemic mixture razoxane (ICRF-159). This compound is much more water soluble and thus could be formulated for parental use. The maximum tolerated dose in children after phase I trials was determined to be 3500 mg/M2/day x 3 days. A phase II trial of ICRF-187 was done in 21 children with solid tumors and 35 children with acute leukemia. All these patients were less than 21 years of age, had recovered from previous chemotherapy, had normal liver and kidney functions, and had a life expectancy of greater than 4 weeks. ICRF-187 was administered at a dose of 3 g/M2/day for 3 days as a 4 hour infusion each day. In patients with leukemia, no objective response was seen in the bone marrow although a few patients had a decrease in peripheral blast count. There were no measurable responses seen in patients with a solid tumor. ICRF-187 was well tolerated. The major toxicity was hematopoietic depression. Significant but rare toxicities included moderate to severe nausea and vomiting, and elevation of bilirubin and transaminases. Although inactive in the current study, ICRF-187 might be more active in another schedule.