Taxol-Induced Cellulitis after Extravasation: A Rarely Reported Event

Am J Oncol (CCT) 20(5):540,1997

The antineoplastic agent paclitaxel (Taxol^®, Mead Johnson, Evansville, IN, U.S.A.) is a complex plant product (a ditrepene) that - with its unique mechanism (induction of tubulin polymerization)- has demonstrated clinical antitumor activity in advanced and refractory ovarian, breast, and lung cancers.¹ The toxicity mostly encountered with its use includes myelosuppression, hypersensitivity reaction, cardiotoxicity, and neuropathy.2 Rarely, local venous effects - including erythema, tenderness, and discomfort along the course of an injected vein - and phlebitis have been described, particularly when large volumes (>50 mL) are infused.² Skin and soft-tissue injuries caused by Taxol^® extravasation have been exhibited sporadically^2-4 and are characterized by pain, erythema, skin ulceration, and cellulitis, followed by sclerosis and hyperpigmentation.^3-5 We describe cellulitis caused by extravasation of intravenously administered Taxol^® in one of our patients.

A 68-year-old woman received a 3-hour infusion of 180 mg Taxol^® (130 mg/m2) as second-line chemotherapy for her metastatic breast cancer. Taxol^® was administered through an implanted PORT-A-CATH (PAC, MID, Ltd., Tel-Aviv, Israel) on the right chest wall. Due to mechanical fault, the dislocated PAC caused extravasation of approximately 200 mg Taxol. Cellulitis with sharply demarcated erythema, local heat, and blisters developed. On catheter removal and institution of antibiotics, the cellulitis disappeared.

Soft-tissue injury, secondary to inadvertent extravasation of chemotherapeutic agents (particularly anthracyclines), nitrogen mustard, mitomycin C, vincristine, vinblastine, and vindesine still constitutes a serious management problem.⁵ Taxol^® is also a vesicant agent that has been described as causing symptomatic and extended soft-tissue injury, histologically resembling coagulative necrosis with minimal inflammatory changes.^1,5 Severe irradiation recall dermatitis and even necrosis at sites of prior Taxol^® extravasation have also been exhibited.³ Proposed mechanisms for Taxol-induced skin and subcutaneous injury are variable and can be related to the Cremophor^® (Mead Johnson, Evansville, IN, U.S.A.) vehicle in which Taxol^® is formulated. Because of its high molecular weight, bulky structure, and avidity for tissue protein, Taxol^® exits tissues slowly (partly because of its microtubule accumulation) and markedly increases local tissue exposure - hence, local injury.^1,5,6 Treatment options are not well documented and protocols focus mainly on minimizing the amount of drug extravasated by aspiration before removing the intravenous catheter, close observation, and the application of warm compresses.

In conclusion, physicians involved in the administration of Taxol^® should be aware of its severe skin and subcutaneous side-effects. Patients receiving Taxol^® should be monitored for extravasation.

Moshe Efraim Stein, M.D.

Kerem Drumea, M.D.

Rasem Abu-Rasmi, M.D.

Nissim Haim, M.D

Northern Israel Oncology Center,Rambam Medical Center

Faculty of Medicine,Technion-Israel Institute of Technology

Haifa, Israel.

Acknowledgement: The authors thank Mrs. M. Perlmutter for her assistance in the preparation of this paper.