Epidemiology and etiology

The incidence of chemotherapy extravasation is generally reported to be between 0.5% and 6% of all chemotherapy-related adverse events.5 A number of risk factors have been identified for chemotherapy extravasation (Table 99-16). Chemotherapy agents are generally classified into three groups: vesicants, irritants, and nonvesicants (Table 99-17).58 Either vesicants or irritants may cause local symptoms, however vesicants cause local tissue necrosis upon extravasation whereas irritants do not. The degree of tissue injury depends on the concentration and amount of fluid extravasated. It is important to note that some agents are well-known vesicants; however, for many agents, only isolated case reports of tissue necrosis exist. Therefore, it is imperative to use caution when administering any chemotherapeutic agent, especially new or in-vestigational agents that have unknown vesicant properties.

Table 99-17 Chemotherapeutic Agents With Vesicant or Irritant Properties

Vesicants

Irritants

Common

Camptotheclns

Anthracyclines

Carmusiine

Daunorublcin

Cyclophosphamide

Doxorubicin

Dacarbazine

Epirubicin

Ep i podophy IJptoxi ns

idarubicln

Etoposlde

Dactinonnycin

Fluorouracll

Mechlorethamlne

Gemcitabine

Mitomycin C

Ifbsfamide

Vinca alkaloids

Irinotecan

Vincristine

.Melphaian

Vinblastine

Pentostatin

Vinorclbine

Streptozocln

Rare"

Teniposide

Cisplatin

Topotecan

Liposomal doxorubicin

Mjjoxarrtrone

Oxallplatin

Taxanes

Docetaxel

Paciitaxel

"Agents for which there aie isolated case reports of local tissue necrosis.

From Ref 58.

PATHOPHYSIOLOGY

The mechanism of tissue injury is related to the pharmacodynamic characteristics of the extravasated drug. These agents may be classified into DNA-binding and non-DNA-binding. Examples of DNA-binding agents include the anthracyclines, me-

chlorethamine, and mitomycin C. These agents first cause cell death through interactions with DNA, and are then released into the surrounding tissue and taken up by adjacent cells. This repeating cycle is perpetuated by the lipophilic nature of these drugs resulting in chronic, slow-healing tissue injury due to long tissue retention. Doxorubicin in particular may remain in tissues for weeks to months.58

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