Phase I dose escalation of doxorubicin chemotherapy in tumor-bearing equidae.

This study examines the effects and the maximum tolerable dosage of the chemotherapy drug doxorubicin in horses with tumors. After a series of treatments, the researchers found that a dose of 70 mg/m(2) every three weeks was most effective and recommended usage of antihistamines and nonsteroidal anti-inflammatory drugs alongside the chemotherapy to control any hypersensitivity.

Research Objectives and Methodology

• The main goal of the research was to establish the highest possible dosage of doxorubicin that horses with tumors could withstand without adverse effects. This is referred to as the ‘maximum tolerated dose’ (MTD).
• The researchers used a two-stage dose-ranging design, increasing the dosage both within individual horses (intrapatient) and across multiple horses (interpatient).
• The treatment protocol consisted of six cycles administered at three-week intervals. The dosage varied from 40 to 85 mg per square meter.
• The team monitored the horses for any clinical signs and changes in both hematological factors (relating to their blood) and non-hematological factors (non-blood related).

Research Findings

• Twelve horses completed the full treatment protocol, receiving total doses ranging from 1127 to 2900 mg.
• The MTD of doxorubicin for horses was found to be 75 mg per square meter.
• The main limiting factors for dosage were hypersensitivity reactions and neutropenia (an abnormally low count of a type of white blood cell).
• The hypersensitivity observed was directly related to the dose, but not to the scheduling of treatments.
• Neutropenia was influenced by both the dose and the cycle of treatment, but not by the escalation schedule.
• No evidence of cardiotoxicity (potential harm to the heart) was observed.

Conclusion and Recommendation

• The researchers suggest a dosage of 70 mg/m(2) doxorubicin every three weeks for treating horses with tumors.
• They also recommend the use of antihistamines and nonsteroidal anti-inflammatory drugs as a combination treatment to control hypersensitivity caused by doxorubicin.