Phase 1 Dose Escalation of Single-Agent Mechlorethamine in Dogs With Lymphoma

Area of Science:

• Veterinary Oncology
• Pharmacology
• Canine Cancer Research

Background:

• Mechlorethamine is a chemotherapy drug commonly used in dogs at 3 mg/m².
• Minimal toxicity at current doses suggests higher mechlorethamine levels may be tolerable in canine patients.

Purpose of the Study:

• Determine the maximally tolerated dose (MTD) of mechlorethamine in dogs diagnosed with lymphoma.
• Characterize the toxicity profile associated with escalating mechlorethamine doses.
• Evaluate treatment response in chemotherapy-naïve dogs receiving mechlorethamine at the MTD.

Main Methods:

• A 3+3 dose escalation study design was employed, enrolling dogs with confirmed lymphoma.
• Mechlorethamine was administered intravenously, starting at 3.5 mg/m² with planned dose increments.
• Adverse events were monitored using VCOG-CTCAE guidelines to define dose-limiting toxicity.

Main Results:

• Thirty dogs were enrolled across nine dose cohorts.
• The maximally tolerated dose (MTD) was determined to be 10.7 mg/m², with grade 4 neutropenia observed at 12.3 mg/m².
• Six of ten chemotherapy-naïve dogs showed partial responses (PR) at the MTD; low-grade gastrointestinal toxicities were manageable.

Conclusions:

• Higher doses of mechlorethamine can be safely administered as a single agent to dogs compared to previously reported levels.
• Increasing mechlorethamine dosage may enhance therapeutic outcomes in canine lymphoma treatment, particularly in combination therapies.