Experimental and Clinical Observations of the Effects of Cytotoxic Chemotherapeutic Drugs on Wound Healing

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Abstract
The administration of perioperative doxorubicin HCl (Adriamycin) had profound effects on wound healing for 5 out of 7 breast cancer patients and 5 of 5 melanoma patients following intravenous and intra-arterial infusional chemotherapy, respectively. The clinical observation of significant reduction in wound tear strength (WTS) and wound tear energy ( WTE ) in the group of patients with cutaneous melanoma initiated this experimental analysis. A study of WTS ( kNm -2) in nontumor-bearing (non-TB) and Morris Hepatoma (MH)-7777 (TB) rats treated with therapeutic doses of Adriamycin (ADR) and methotrexate (MTX) was compared with saline-treated controls. Mean tumor volume (cm3) was unaffected by MTX, while significant tumor inhibition (p less than 0.01) was evident for ADR-treated TB animals. A correlation (r = 0.516, p less than 0.01) was observed for tumor volume and WTS. Separate analysis of TB and non-TB animals identified a significant correlation (r = 0.6259, p less than 0.01) between advancing cachexia in TB rats and WTS. A 21-day analysis was done for 160 animals to determine the effect of MTX and ADR on WTS ( kNm -2) and WTE ( Ncm -1). The presence of MH-7777 significantly (p less than 0.01) reduced WTE for TB animals not treated with chemotherapy. TB animals treated with ADR had significant (p less than 0.01) improvement in WTE at day 21 compared with TB controls. This enhancement in WTE was not observed in rats treated with MTX. These clinical and experimental observations suggest significant retardation of the early phases of wound fibroplasia as determined by WTS and WTE following operative trauma and subsequent administration of therapeutic dosages of cytotoxic agents.