extravasation refers to the unintended leakage of a liquid formulation of a drug from blood vessels into surrounding tissues .
extravasation of anticancer drugs administered by intravenous infusion constitutes a serious adverse event associated with chemotherapy .
in particular , the extravasation of drugs with vesicants , such as anthracyclines , can cause necrosis of the surrounding tissues , often requiring surgical procedures .
in addition to careful observation during treatment , a better understanding of the risks of tissue damage triggered by extravasation is essential to ensure the safety of patients who receive cancer chemotherapy .
the package insert of doxil ( pegylated - liposomal doxorubicin ) cautions that this preparation is an irritant .
however , medical procedures for the management of extravasation reactions and their actual outcomes have not been well documented .
we describe here a patient in whom extravasation of a large volume of doxil was successfully treated by an immediate subcutaneous corticosteroid injection .
a massive extravasation of a doxil injection ( janssen pharmaceutical , tokyo , japan ) accidently occurred during an intravenous infusion of the drug in a 54-year - old woman with heavily treated metastatic ovarian cancer .
the patient was scheduled to receive an intravenous infusion of 75 mg of doxil in a 250 ml 0.9% nacl solution , delivered via a 24-gauge cannula ( surflo i. v. catheters , terumo , tokyo , japan ) placed in the right forearm . before and at the beginning of the infusion , oncology nurses in the outpatient chemotherapy unit confirmed good patency of the vein by checking the blood backflow ; a free flow of the infusion solution was also confirmed .
the patient reported a swelling ( 10 x 20 cm ) with mild erythema gradually spreading around the infusion cannula placed in the right forearm ( fig .
1 ) . she experienced no pain , but did feel numbness . in accordance with the institutional guidelines for the management of the extravasation of vesicant drugs ,
the infusion was terminated immediately , and less than 0.1 ml of the infusion solution and a small amount of blood were slowly aspirated back through the original cannula with the use of a disposable syringe .
after removal of the original cannula , 200 mg of corticosteroid ( solu - cortef , pfizer , tokyo , japan ) and 50 mg of lidocaine ( 1% xylocaine , astrazeneca , tokyo , japan ) diluted with 0.9% nacl solution to a total volume of 20 ml were injected subcutaneously via a 27-gauge needle into the extravasation site and surrounding tissues .
the affected site was then topically applied with clobetasol propionate ( dermovate ointment , glaxosmithkline , tokyo , japan ) and cooled with an icepack for 30 minutes . immediately after the extravasation of doxil .
three days after extravasation the swelling decreased , and erythema of the extravasation site became faint .
four weeks after extravasation , the erythema had faded , and a mild epithelial desquamation remained around the extravasation site ( fig .
the erythema had resolved , and the wound had healed with no apparent sequela . there were no serious complications such as tissue necrosis or ulceration .
this case report provides valuable information on the characteristics and successful management of extravasation reactions caused by doxil , an intravenous anticancer drug used to treat refractory ovarian cancer .
in contrast to conventional liposomes , the introduction of this novel delivery system allows pegylated - liposomal doxorubicin to evade detection and destruction by the body s immune system .
the drug thus remains in the systemic circulation for a prolonged period , with an elimination half - life of approximately 55 hours .
though doxorubicin is thought to be preferentially released from the pegylated - liposomes into tumor tissues , the exact mechanism involved is not fully understood .
owing to a modification of the formulation , extravasated doxil is categorized as an irritant , even though doxorubicin per se is a well - known vesicant .
although the package insert states that doxil is an irritant , we took all necessary precautions and administered all the treatments currently available in japan because the extravasation was massive , and doxorubicin per se is classified as a vesicant .
other antidotes , such as dimethyl sulfoxide ( dmso ) , hyaluronidase , or dexrazoxane , have been used to treat extravasation reactions , but they are not currently approved in japan . although the mechanism by which corticosteroids ameliorate extravasation reactions remains unclear , these drugs have been used to manage extravasation injury caused by various drugs . in our patient ,
an immediate subcutaneous corticosteroid injection apparently contributed to preventing tissue necrosis and other potentially serious complications .
 abstracta massive extravasation of pegylated - liposomal doxorubicin ( doxil ) accidentally occurred , affecting the right forearm of a 54-year - old woman with metastatic ovarian cancer who was receiving an intravenous infusion of the drug . in accordance with the institutional guidelines for vesicant drugs , 
 a corticosteroid preparation was immediately injected subcutaneously into the surrounding tissues . 
 clobetasol propionate and an ice pack were then topically applied to the affected region . 
 there were no serious complications at the extravasation site , such as tissue necrosis or severe pain , and only a transient erythema of the skin and desquamation remained after 2 months . 
INTRODUCTION
CASE REPORT
DISCUSSION
Conflicts of interest