Docetaxel


Article Author:
Nicole Farha


Article Editor:
Anup Kasi



Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
5/23/2019 7:51:54 AM

Indications

Docetaxel, in combination with cisplatin, is approved as a first-line agent in the treatment of prostate cancer.[1] It is the standard of care in patients with castration-resistant prostate cancer for palliation and prolongation of life.[2] Single-dose docetaxel is generally first-line therapy in patients with non-small cell lung cancers and poor performance status.[1] Docetaxel is especially effective in preventing progression and extending survival in non-small cell lung cancer patients with metastatic disease, as it has a good tolerability profile. Docetaxel serves as a standard adjunct agent in the treatment of breast cancer, demonstrating significant improvements in survival in high-risk patients regardless of prognostic factors such as the expression of estrogen receptor, the degree of nodal involvement, age, menopause status, and schedule of administration.[3] Finally, together with oxaliplatin and capecitabine, docetaxel completes the triple-agent combination therapy known as the TEX regimen and is indicated for treating advanced gastric cancer.[4]

Mechanism of Action

Docetaxel is a second-generation chemotherapeutic agent of the taxane family.[1] A derivative of paclitaxel, the first taxane to hit the market,[2] docetaxel’s primary mechanism of action is to bind beta-tubulin, enhancing its proliferation and stabilizing its conformation. Doing so inhibits the proper assembly of microtubules into the mitotic spindle, arresting the cell cycling during G2/M. Docetaxel also reduces the expression of the BCL2 gene, an anti-apoptotic gene often over-expressed by cancer cells conferring enhanced survival. By downregulating this gene, tumor cells can more readily undergo apoptosis.[1]

Administration

When administered intravenously, docetaxel's possible dosing schedules have considerable variability. It can be administered as a one-time single dose or as regular doses given at increments varying from once weekly to once every five weeks. Dosing regimen depends on the cancer type and level of treatment aggressiveness.[1][5][6][3] Weekly administration is generally restricted mostly to palliation of patients with metastatic disease.[7] The mechanism of administration of docetaxel plays a role in minimizing potential toxicity.[8][9] Administering the drug loaded onto liposomes or micelles enhances the selective uptake by cancer cells expressing certain cellular markers, optimizing intracellular concentration.[8]

Adverse Effects

Common adverse effects seen in patients treated with docetaxel include infusion reactions, myelosuppression, febrile neutropenia, fatigue, diarrhea, and fluid retention.[7] Infusion reactions can range from standard flushing, itching, dyspnea, and fever to potentially life-threatening anaphylactic shock and cardiorespiratory arrest.[7] Myelosuppression is common with the use of cytotoxic drugs. With docetaxel, anemia, neutropenia, leukopenia, and thrombocytopenia are all reported.[1][3] Systematic review and meta-analysis of docetaxel use in non-small cell lung cancer patients showed a significantly increased risk of severe infections, defined as grade 3 or higher, which is a potentially life-threatening adverse effect, thought to be related to the cytotoxicity exerted on the immune system.[1] Febrile neutropenia is also among the more serious adverse effects, as it is associated with significant morbidity and mortality when not properly managed.[7]

Patients often experience skin toxicities with docetaxel use. Namely, acral erythema, characterized by tingling in the palms and soles followed by edema and tenderness, and erythrodysesthesia, where fixed solitary plaques develop on the skin adjacent to the infusion site, are the most commonly seen.[7] Peripheral neuropathy, both sensory and motor, is arguably the most common long-term side effect of docetaxel,[7] and this neuropathy, along with fatigue and neutropenia, is often the dose-limiting factor that causes patients to defer further treatment.[5][2] And finally, myalgias and arthralgias are a known adverse effect of docetaxel and other drugs in the taxane family; cases reports exist of myositis associated with docetaxel, though this is rare.[10]

Docetaxel is known to confer resistance in multiple types of solid tumors. Through the alteration of blood vessels impairing drug distribution, efflux pumps decreasing intracellular drug concentration, alterations in microtubule structure or function evading stabilization by the drug, or the upregulation of anti-apoptotic pathways, tumors eventually adapt to survive the once-lethal environment created by docetaxel. These adaptations are another treatment-limiting factor that comes into play with long-term chemotherapy administration.[2]

Contraindications

Treatment with taxanes is relatively contraindicated in patients with pre-existing lung conditions, such as COPD.[7] A common complication accompanying taxane treatment is pulmonary toxicity. Pulmonary complications can be life-threatening, especially in predisposed patients with compromised lung function, so, for this reason, avoidance is necessary if possible. Additionally, prior to administration of therapy, patients are screened for renal, hepatic, and bone marrow function to establish potential drug tolerability, and that side effects of treatment will be manageable.[7]

Monitoring

Following infusion of docetaxel, patients receive monitoring for infusion reactions, skin toxicities, fever and other signs of infection, and signs of pneumonitis. Additionally, severe diarrhea or new onset abdominal pain should warrant further evaluation and a possible surgical consultation, as these patients are at an increased risk for bowel perforation.[7] Patients are also advised to monitor for signs of increased fluid accumulations such as swelling in the fingers, ankles, and mid-abdominal areas. Increased permeability of the capillaries is purported to cause fluid retention.[7] Swelling can be an indication for the administration of dexamethasone or diuretics to limit progression to more severe conditions of fluid retention, such as pleural or pericardial effusion.

Toxicity

Dose-dependent pulmonary toxicity has been associated with the administration of docetaxel.[7] Acute, bilateral interstitial pneumonitis has been demonstrated to occur during, immediately following, and even long after the initial administration of the drug. Symptoms include dyspnea on exertion, a dry cough, fever, and malaise. The mechanism of action underlying this pulmonary toxicity is poorly understood, but it is believed to be an immune-mediated reaction to the drug.[7] In treating this toxicity, supportive care usually is sufficient to bring patients back to their baseline lung function. However, in patients showing clinical signs of either oxygen desaturation or possible respiratory failure, an empiric trial of glucocorticoids has proven effective in relieving pneumonitis.

Enhancing Healthcare Team Outcomes

A broad range of clinical expertise plays a role in the treatment of cancer. Medical oncologists, radiation oncologists, specialists of involved systems (i.e., urologists in prostate cancer), and supporting staff all play a role in the optimization of treatments and outcomes, based on patients’ needs and wishes. Proper monitoring, managing adverse events and acquired comorbidities, and counseling and education on the various treatment options and all that they entail can all be considered multidisciplinary responsibilities. The delivery of patient-centered care requires active coordination and regular correspondence between multiple disciplines of care.[11] [Level V]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Docetaxel - Questions

Take a quiz of the questions on this article.

Take Quiz
A patient is treated with systemic chemotherapy for breast cancer. Treatment involves a drug that binds and stabilizes the tubule to confer cytotoxicity. Which of the following adverse events is most likely to be life-threatening in this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient presents with metastatic but hormonally sensitive prostate cancer. What is the expected median benefit in survival of a combination of 6 cycles of docetaxel with androgen deprivation therapy, compared to treating with androgen deprivation therapy alone?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Your patient receives docetaxel for prostate cancer. Myelosuppression is a concern with this medication. Which of the following would result from for this adverse event?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with castration-resistant prostate cancer desires a chemotherapeutic agent for palliation and prolongation of life. The provider caring for this patient considered treatment with docetaxel, but quickly realized it was contraindicated. Which of the following comorbidities does this patient most likely have?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with advanced gastric cancer is being considered for treatment using the triple-therapy TEX regimen. Which of the following describes a mechanism of action of one of the three contributing drugs?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 68-year-old male presents with a history of new-onset shortness of breath, dry cough, and fever. He is currently being treated for castration-resistant prostate cancer and has a history of chronic kidney disease and emphysema. He is ultimately diagnosed with pneumonitis, which is relieved by empiric glucocorticoid treatment. Which of the following treatments is most likely the underlying cause for this toxicity?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Docetaxel - References

References

Du Q,Jiang G,Li S,Liu Y,Huang Z, Docetaxel increases the risk of severe infections in the treatment of non-small cell lung cancer: a meta-analysis. Oncoscience. 2018 Jul     [PubMed]
Antonarakis ES,Armstrong AJ, Evolving standards in the treatment of docetaxel-refractory castration-resistant prostate cancer. Prostate cancer and prostatic diseases. 2011 Sep     [PubMed]
Kim SB,Sayeed A,Villalon AH,Shen ZZ,Shah MA,Hou MF,Nguyen Ba D, Docetaxel-based adjuvant therapy for breast cancer patients in Asia-Pacific region: Results from 5 years follow-up on Asia-Pacific Breast Initiative-I. Asia-Pacific journal of clinical oncology. 2016 Jun     [PubMed]
Ostwal V,Bose S,Sirohi B,Poladia B,Sahu A,Bhargava P,Doshi V,Dusane R,Nashikkar C,Shrikhande SV,Ramaswamy A, Docetaxel/Oxaliplatin/Capecitabine (TEX) triplet followed by continuation monotherapy in advanced gastric cancer. Indian journal of cancer. 2018 Jan-Mar     [PubMed]
Parikh M,Pan CX,Beckett LA,Li Y,Robles DA,Aujla PK,Lara PN Jr, Pembrolizumab Combined With Either Docetaxel or Gemcitabine in Patients With Advanced or Metastatic Platinum-Refractory Urothelial Cancer: Results From a Phase I Study. Clinical genitourinary cancer. 2018 Jul 12     [PubMed]
Sakaguchi M,Maebayashi T,Aizawa T,Ishibashi N, Docetaxel-induced radiation recall dermatitis with atypical features: A case report. Medicine. 2018 Sep     [PubMed]
Kushwah V,Jain DK,Agrawal AK,Jain S, Improved antitumor efficacy and reduced toxicity of docetaxel using anacardic acid functionalized stealth liposomes. Colloids and surfaces. B, Biointerfaces. 2018 Aug 23     [PubMed]
Varshosaz J,Enteshari S,Hassanzadeh F,Hashemi-Beni B,Minaiyan M,Sadeghian-Rizi S, Synthesis And In Vitro/In Vivo Characterization Of Raloxifene Grafted Poly(Styrene Maleic Acid)-Poly (Amide-Ether-Ester-Imide¬¬) Micelles For Targeted Delivery Of Docetaxel In G Protein-Coupled Estrogen Receptor Breast Cancer. Anti-cancer agents in medicinal chemistry. 2018 Sep 5     [PubMed]
Ho MY,Mackey JR, Presentation and management of docetaxel-related adverse effects in patients with breast cancer. Cancer management and research. 2014     [PubMed]
Bahl A,Bellmunt J,Oudard S, Practical aspects of metastatic castration-resistant prostate cancer management: patient case studies. BJU international. 2012 Mar     [PubMed]
Thomas J,Warrier A,Kachare N, Docetaxel-Induced Myositis. Journal of clinical rheumatology : practical reports on rheumatic     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of your specialty. When it is time for the board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study.