Extravasation Of Chemotherapeutic Agents

The extravasation of intravenously administered chemotherapeutic agents into the subcutaneous tissue of cancer patients undergoing chemotherapy is a known risk of treatment. The potential gravity of injury caused by extravasation is dependent upon the type of drug which extravasates. The most destructive extravasation injuries are those caused by anti-tumor drugs which bind to deoxyribonucleic acid (DNA), such as Doxorubicin, (Adriamycin) which has been a primary part of chemotherapeutic regimes since the late 1960's. Extravasation of chemotherapeutic agents which bind to nucleic acids can lead to a prolonged course of injury. The most clinical experience has been derived from the extravasation of Doxorubicin. Rudolph, R, Larson, D. Etiology and Treatment of Chemotherapeutic Agent Extravasation Injuries: A Review. J. Clin. Oncol, 1987; 5:1116-1126. Doxorubicin causes severe progressive tissue necrosis that may involve muscles and tendons. Since no specific antidote has been developed, the recommended treatment of Doxorubicin extravasation is early excission of all infiltrated tissue. Dahlstrom, KK, Chenoufi, HL, Daujard, S. Fluorescene microscopic demonstration and demarcation of Doxorubicin extravasation. Experimental and Clinical studies. Cancer, 1990 Apr. 15; 65(8): 1722-1726.

It has been postulated that infiltration of Hyaluronidase, which may serve to dilute the extravasated Doxorubicin, will decrease the amount of ulceration caused by the extravasation. Disa JJ, Chang RR, Mucci JJ, Goldberg N.H., Prevention of Adriamycin-induced full-thickness skin loss using hyaluronidase infiltration. Plast. Reconstr. Surg. 1998 Feb., 101(2):370-374. In this regard the injection of saline solution at the site of extravasation of a vesicant (blistering) chemo-therapeutic agent in order to reduce the concentration of the extravasated drug has been reported to have been effective. Scuderini, Onesti MG, Anti-tumor agents: Extravasation, Management and Surgical Treatment. Am. Plast. Surg. 1994 Jan; 32(1):39-44. However, other authors have emphatically stated not to inject saline, sodium bicarbonate or hyaluronidase into the extravasation area as to do so may increase the diffusion of the extravasated agent into surrounding tissue. Hankin FM, Louis DS, Extravasation of Chemotherapeutic Agents. Am. Fam. Phys. 1985 March; 31(3)147-150.

For some time the injection of steroids into the subcutaneous tissue at the site of Doxorubicin extravasation was recommended on the theory that steroids would reduce inflammation. However, it has been demonstrated that inflammatory cells are uncommon in tissue damaged by Doxorubicin extravasation. Rudolph R, Stein RS, Patillo R: Skin Ulcers Due to Adriamycin. Cancer 38:1087-1094, 1976; Larson DL: What is the appropriate treatment of tissue extravasation by anti-tumor agents? Plast Reconstr Surg 75:397-405, 1985. In 1996 the package insert for Adriamycin was changed. Prior thereto, the injection of steroids was recommended in the event of extravasation. In 1996 it was stated that the benefit of local administration of drugs has not been clearly established. Close observation and plastic surgery consultation were recommended. The immediate treatment of DNA-binding chemotherapy extravasation should include elevation of the effected extremity and intermittent cold. There does not seem to be any agent that, injected locally, can alter the final result from extravasation of any binding chemotherapeutic agent. Persistent swelling, erythema and pain are indications for surgical consultation, even if ulceration is not yet apparent. Such consultation is mandatory when blistering and ulceration are first seen. Rudolph and Larson, supra. Snyderman RK, Krasna MJ, Adriamycin extravasation injuries. Plast Reconstr Surg 1986 Apr; 77(4):683-684.

For a discussion of a case involving Failure to properly treat extravasation of doxorubicin (Adriamycin). Click here.

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