Clinical Pharmacy & Pharmacogenomics Life

來　跟小風念一次：Docetaxal (doe se TAKS el)

今天因緣際會下　被學妹問到這一題...

Dexamethasone 與 Docetaxel 併用，主要可以預防：

(A) 低血壓 (hypotension)
(B) 水腫 (edema)
(C) 氣喘 (asthma)
(D) 噁心 (nausea)

Ans: (B) 水腫 (edema)

在開始黑白講之前　還是要照例聲明一下

【本內容僅供參考，請以 textbook 或 guideline 為主】

【臨床藥學與治療學是複雜多變的，解析僅為零碎片段，非為完整觀念】

抗癌藥品項多　每種特性也都不大一樣　
因此很複雜　也很不好懂　 (￣ε(#￣) #○=(一-一o)

抗癌藥有許許多多的副作用　國際上也有專門為其訂製分級制度的共識

" Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 "

其中將抗癌藥造成的不良反應按嚴重程度分為 Grade 1 ~ 5
而通常 Grade 5 就代表... 往生　  (￣□￣|||)a

然而，雖然許多藥物不良反應我們無力完全阻止它的發生，但是所幸賴於許多的臨床研究，我們得以藉由適當的調整與輔助藥物的介入來減低或避免可預期的副作用，使得病人得以耐受抗癌藥物之毒性，進而完成治療療程。

許許多多的細胞保護劑以及 premedication 藉此應運而生。

抗癌藥造成的過敏反應 (hypersensitivity reaction) 往往不盡相同，有可能是 hypotension，也有可能是以 pulmonary/peripheral edema 等型態表現。所以我們常以 clinical study 做出來的 protect or prevent efficacy 結果來設計各個抗癌藥應有的 premedication。

Docetaxel (Taxotere)

FDA-Labeled Indication
　- Breast cancer, Adjuvant tx in comb w/ doxorubicin & cyclophosphamide
　　for pt w/ operable node-positive d'z
　- Breast cancer, Locally advanced/metastatic d'z, after failure of prior C/T
　- Gastric cancer
　- Head & neck cancer, Locally advanced SqCC, induction tx in comb w/
　　cisplatin & 5-FU
　- Hormone refractory prostate cancer, Metastatic, in comb w/ prednisone
　- NSCLC, Locally advanced/metastatic d'z, as monotherapy after failure
　　of prior platinum-based C/T
　- NSCLC, Unresectable, locally advanced/metastatic d'z, 1st-line tx in
　　comb w/ cisplatin

Adverse Effects
　Common
　　* CV: Edema (47-64%), vasodilatation (27%)
　　* Dermatologic: Alopecia (56-98%), Disorder of nail (11-18%), skin
　　　　　　　　　　and/or subQ tissue, Nail changes (8-31%), pruritus, rash 
　　* GI: Diarrhea (33-43%), nausea (39-81%), stomatitis (42-69%),
　　　　　vomiting (22-44%)
　　* Hematologic: Anemia (89-94%), leukopenia (96-99%),
　　　　　　　　　　neutropenia (71-99%)
　　* Reproductive: Amenorrhea (62%)
　　* Other: FUO (31-46%) 
　Serious
　　* CV: Edema (severe) (6-9%)
　　* Dermatologic: SJS, TEN
　　* GI: Colitis
　　* Hematologic: Anemia (< 8 g/dL) (4-9%), febrile neutropenia (5-25%), 
　　　　　　　　　leukopenia (< 1000 cell/mm3) (32-44%), neutropenia
　　　　　　　　　(ANC < 500 cell/mm3) (66-86%), thrombocytopenia (8-9%)
　　* Hepatic: hepatotoxicity
　　* Immunologic: anaphylaxis (rare)
　　* Renal: renal failure
　　* Respiratory: Interstitial pneumonia, pulmonary embolism
　　* Other: Infectious d'z (22-39%)

在拙作抗癌筆記中雖有提到，但礙於空間，所以寫的不是很清楚。

 o(＞＜；)o o

我們來看看 Lexi-comp Drug Information Handbook 的內容吧~

[ Warnings / Precautions ]

Severe hypersensitivity reactions characterized by rash/erythema, hypotension, bronchospasms, or anaphylaxis may occur; minor reactions including flushing or localized skin reactions may also occur.

Fluid retention syndrome characterized by pleural effusions, ascites, edema, and weight gain (2-15 kg) has also been reported.

The incidence & severity of the syndrome increase sharply at cumulative doses > or = 400 mg/m².

Pt should be premedicated w/ a corticosteroid to prevent hypersensitivity reactions & fluid retention; severity is reduced w/ dexamethasone premedication starting one day prior to docetaxel administration.

[ Additional Information ]

Premedication w/ oral corticosteroids is recommended to decrease the incidence & severity of fluid retention (pulmonary/peripheral edema) and severity of hypersensitivity reactions.

Dexamethasone 8-10 mg PO BID for 3-5 days, starting the day before doxetaxel administration, is usually recommeded.

小結：

藥物的作用到底是好是壞，就看你怎麼去運用它。 <(￣︶￣)>

的確，steroid 在長期使用或是某些特殊病況的病人的確容易造成水腫的問題，但是在投予 docetaxel 前使用之，乃是希望藉由其抗發炎之藥理作用，減輕後者引起之過敏反應及 pulmonary/peripheral edema。

~(￣▽￣)~(＿△＿)~(￣▽￣)~(＿△＿)~(￣▽￣)~

[ Abbreviations ]

comb - combination, combinate
C/T - chemotherapy
CV - cardiovascular
d'z - disease(s)
FUO - fever of unknown origin
GI - gastrointestinal
NSCLC - Non-small cell lung cancer
pt - patient(s)
SJS - Stevens-Johnsons syndrome
SqCC - Squamous cell cancer
SubQ - subcutaneous
TEN - Toxic epidermal necrolysis
tx - treatment, therapy 
UNL - upper limit of normal
w/ - with
w/o - without