Effects of cyclophosphamide and adriamycin on the healing of surgical wounds in mice.

Administration of therapeutic dose levels of cyclophosphamide as a single dose or as daily treatments for 5 days during the perisurgical period resulted in a significant decrease in the strength of surgical skin wounds in mice as measured 21 days after surgery. Administration of a single dose of 200 mg/kg either at the time of surgery or up to 4 days prior to or after surgery impaired 21-day wound strength, with the most extensive depression observed when the drug was given 1 or 2 days after surgery. Earlier stages of wound healing (day 3 or day 7) were not as sensitive to cyclophosphamide. Adriamycin in the therapeutic dosage range for mice did not significantly impair wound healing. This drug had an effect only at the LD10 dosage level. Combination treatment with cyclophosphamide plus adriamycin at the time of surgery impaired 21-day wound strength to a greater degree than observed with either agent alone, but did not significantly depress wound strength 3 or 7 days after surgery. These studies indicate that dosage level, the time of drug administration relative to surgery, and the time at which wound strength measurements are made are important parameters in determination of the effects of antineoplastic agents on wound healing.