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Premedication with 20 mgdexamethasone effectivelyprevents relapse of extensiveskin rash associated withgemcitabine monotherapy

Gemcitabine treatment is commonly associated with skinrash, with a reported incidence of 7%–30% [1–3];however, there exists only one prior report describing themanagement of gemcitabine-associated rash in theEnglish-language literature [1]. When an extensive skinrash develops, both the patient and physician may experience anxiety about continuing gemcitabinetreatment. For patients with a toxic drug-induced rash,continued administration of that drug may exacerbate therash and put the patient at the risk of a more severe toxicevent, such as toxic epidermal necrosis (TEN). From April2008 to April 2009, we treated 107 patients withgemcitabine monotherapy and experienced four T

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   c   o   p   e   n    i   a .

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 Volume 21 | No. 1 | January 2010 letters to the editor | 189

8/14/2019 Premedication with 20 mg dexamethasone

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consecutive patients with extensive skin rash associated withgemcitabine. Pretreatment with 4–8 mg i.v. dexamethasonewith or without an antihistamine was not sufficient to preventgemcitabine-induced skin rash. However, when 20 mgdexamethasone was given i.v. before gemcitabine rechallenge,there was no relapse in any case (Table 1). Below, we describeone representative case (patient 4 in Table 1).

case 1

A 72-year-old man with advanced pancreatic cancer wasundergoing gemcitabine monotherapy at a local hospital. Afterthe first administration of gemcitabine, he developed extensiveskin rash, so gemcitabine was discontinued in light of the risk of severe toxic events. The patient was thereafter treated withoral fluorouracil (S-1). Nine months later, he became refractory to S-1 and was referred to Kyoto University Hospital for furthertreatment. Given that gemcitabine has been administeredonly once previously, it was decided to attempt gemcitabinerechallenge. For the first readministration of gemcitabine(1000 mg/m2), the patient was premedicated with 8 mg of dexamethasone i.v., but he again experienced extensive skinrash on his trunk and extremities. After recovery from the skinrash, a second readministration was attempted, with 20 mgdexamethasone premedication. The patient developed neithera skin rash nor a toxic reaction. Gemcitabine treatment (ondays 1, 8 and 15 of each 28-day cycle) was continueduneventfully thereafter with 20 mg dexamethasonepremedication before each gemcitabine administration.

Given the incidence of gemcitabine-associated skin rash, weassume that there have been many cases in which gemcitabinehas been discontinued because of this adverse event. However,exclusion of gemcitabine leaves few effective chemotherapy options, especially for patients with pancreatic and biliary tractcancer. Obviously, this is most disadvantageous for the

patient. To the best of our knowledge, there has only beenone reported case of TEN associated with gemcitabinemonotherapy [4]. In that case, the patient developed TEN afterthe first gemcitabine administration and the genital area was

also affected. In our four cases, the mucosal lesions were intact.Since TEN usually involves the mucosal area, it is possible todistinguish between TEN and a simple extensive skin rash.The mechanism underlying the development of gemcitabine-associated rash is poorly understood; however, it seems to bedifferent from that for toxic skin rash [1]. Furthermore, therisk of TEN associated with gemcitabine rechallenge isvery low. Therefore, in special cases with no therapeutic

alternatives, premedication with 20 mg dexamethasone can beconsidered.

funding

Smoking Research Foundation, Japan.

M. Kanai1*, S. Matsumoto1, T. Nishimura1, Y. Matsumura2

E. Hatano3, A. Mori3, T. Masui3, Y. Kawaguchi3, E. Nakamura4,

S. Tada5, T. Kitano1, H. Ishiguro1, K. Yanagihara1 & T. Chiba1,5

1Outpatient Oncology Unit, Departments of  2Dermatology, 3Surgery,4Urology and 5Gastroenterology, Kyoto University Hospital, 54 Shogoin-

Kawahara-cho, Sakyo-ku, Kyoto, Japan(*E-mail: kanai@kuhp.kyoto-u.ac.jp)

references

1. Chen YM, Liu JM, Tsai CM et al. Maculopapular rashes secondary to

gemcitabine injection for non-small-cell lung cancer. J Clin Oncol 1996; 14:

1743–1744.

2. Burris HAIII, Moore MJ, Andersen J et al. Improvements in survival and clinical

benefit with gemcitabine as first-line therapy for patients with advanced pancreas

cancer: a randomized trial. J Clin Oncol 1997; 15: 2403–2413.

3. Okada S, Ueno H, Okusaka T et al. Phase I trial of gemcitabine in patients with

advanced pancreatic cancer. Jpn J Clin Oncol 2001; 31: 7–12.

4. Mermershtain W, Cohen AD, Lazarev I et al. Toxic epidermal necrolysis associated

with gemcitabine therapy in a patient with metastatic transitional cell carcinoma of

the bladder. J Chemother 2003; 15: 510–511.

doi:10.1093/annonc/mdp513Published online 4 November 2009

letters to the editor Annals of Oncology

190 | letters to the editor Volume 21 | No. 1 | January 2010