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Taxanes

Authors: Dr Daniel Mazzoni, Resident Medical Officer, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia; Dr Nicholas Lucarelli, Resident Medical Officer, Eastern Health, Melbourne, VIC, Australia. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. May 2020.


What are taxanes?

Taxanes are a class of chemotherapeutic agents used in the treatment of some cancers [1]. They were first derived from the bark of the yew trees.

Two of the most common taxanes used in clinical practice are docetaxel and paclitaxel [2]. 

How do taxanes work?

Taxanes induce antineoplastic activity. They inhibit mitosis by interfering with microtubule formation during cell division. By targeting cells with a high turnover, they can slow the growth of solid organ tumours [3].

What are the clinical uses for taxanes?

Taxanes are used in an adjuvant setting or as a primary treatment of cancer [2]. They are administered intravenously every week (paclitaxel) or every three weeks (docetaxel).

They are used for the primary treatment of [2]:

  • Breast cancer
  • Castration-resistant prostate cancer
  • Non-small cell lung cancer
  • Gastric cancer
  • Pancreatic cancer
  • Head and neck cancer
  • Cervical cancer
  • Ovarian cancer
  • Urothelial cancer.

They can also be used in conjunction with other chemotherapy agents.

What are the adverse effects of taxanes?

Like other cytotoxic agents, the side effects of taxanes largely affect organ systems with high mitotic turnover rates.

The most common adverse effects are [4,5]:

  • Fatigue
  • Body aches
  • Loss of appetite.

Other adverse effects include [4,5]:

  • Nausea, vomiting, and diarrhoea
  • Peripheral sensory neuropathy
  • Neutropenia
  • Cutaneous effects.

What are the cutaneous adverse effects of taxanes?

Adverse cutaneous reactions occur in most patients on taxane therapy. They arise more frequently with docetaxel than with paclitaxel [2]. Taxanes affect hair, nails, mucosa, and skin. Most adverse effects are of mild to moderate severity and are usually dose-dependent (depending on the frequency of dosing, the dose intensity, and the cumulative dose). Symptoms usually resolve spontaneously after cessation of taxane therapy [2,6].

Adverse cutaneous effects of chemotherapy
 

Hair loss from taxanes

Taxanes cause acute reversible alopecia, also known as chemotherapy-induced alopecia [2,7].

  • Diffuse hair loss occurs in approximately 60% of patients, usually after the first chemotherapy cycle.
  • Taxanes result in thinning of scalp hair and may affect other hair-bearing areas with higher doses or prolonged therapy.
  • Hair growth tends to recover 3–6 months after therapy, but a few cases of permanent or irreversible alopecia due to taxanes have been reported.

Nail changes due to taxanes

Nail disorders occur in 35–44% of patients receiving taxane therapy [2]. Onycholysis is characteristic. Other drug-induced nail abnormalities include [2,8,9]:

  • Hyperpigmentation (diffuse melanonychia)
  • Koilonychia
  • Nail ridging and fissures
  • Beau lines
  • Periungual tissue formation.

Nail disease due to taxanes is generally cumulative. It tends to resolve within a few weeks after discontinuing taxanes [8].

Mucositis caused by taxanes

Mucositis due to taxanes is common, particularly stomatitis. Dysgeusia may also occur, typically within the first week of therapy [2].

Adverse effects of taxanes in the skin

Skin toxicities due to taxanes are broad with various manifestations as described below [2].

Types of skin reaction to taxanes

Hypersensitivity reaction

  • Hypersensitivity occurs in 30–40% of courses of taxanes, with 95% of reactions occurring during or after the first or second infusion.
  • Reactions can be either immediate or non-immediate, ranging from mild itch and erythema to anaphylaxis.
  • Premedication with antihistamines and systemic corticosteroids at the time of administration reduces the incidence of cutaneous reactions by 5–10%.
  • Cautious re-exposure is possible after a mild hypersensitivity reaction.
  • Taxanes can cross-react, although several case reports have reported resolution of symptoms after switching taxanes [2,10].

Maculopapular or morbilliform rash

  • Docetaxel may cause a morbilliform rash in postadjuvant cases of breast cancer.
  • It typically presents as painful red patches in warm sites prone to microtrauma, including the axillary, groin, and neck folds.
  • Paclitaxel-induced rashes may occur over the extensor surfaces of the limbs [2].

Dorsal hand-foot syndrome

  • Taxane-related hand-foot syndrome has an atypical and unique presentation.
  • It is characterised by a red scaly rash over the dorsal hands, whereas hand-foot syndrome usually affects the palms and soles.
  • It may also affect the thenar eminences and dorsum of the feet.
  • Docetaxal may cause onycholysis [2].

Drug-induced subacute cutaneous lupus erythematosus

  • Drug-induced subacute cutaneous lupus erythematosus presents with an erythematous maculopapular rash on photosensitive areas.
  • Tests typically reveal anti-SSA and anti-Ro antibodies.
  • A skin biopsy can confirm the diagnosis.
  • The rash resolves when the therapy is stopped [2,11].

Pustular rashes

Scleroderma

  • Scleroderma is more likely to occur with docetaxel than paclitaxel.
  • It affects the extremities, particularly the lower limbs, and may result in reduced joint mobility and trophic leg ulcers.
  • It is associated with reversible bilateral pitting leg oedema that resolves on cessation of therapy [12].

Recall inflammatory reactions

  • Radiation recall, intravenous recall, and extravasation recall dermatitis due to taxanes have been reported.
  • Radiation recall is characterised by erythema, swelling, and skin breakdown at the site of previous radiotherapy [2].

Serpentine supravenous hyperpigmentation

  • Serpentine supravenous hyperpigmentation has been rarely reported in association with taxanes.
  • It is characterised by discolouration along the course of superficial venous networks spreading from the initial infusion site.
  • It causes a pruritic or burning sensation [13].

Drug phototoxicity

Other adverse reactions to taxanes include:

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Related information

 

References

  1. Gelmon K. The taxoids: paclitaxel and docetaxel. Lancet 1994; 344: 1267–72. doi: 10.1016/s0140-6736(94)90754-4. PubMed
  2. Sibaud V, Leboeuf NR, Roche H, et al. Dermatological adverse effects with taxane chemotherapy. Eur J Dermatol 2016; 26: 427–43. doi: 10.1684/ejd.2016.2833. Journal
  3. Kellogg EH, Hejab NMA, Howes S, et al. Insights into the distinct mechanisms of action of taxane and non-taxane microtubule stabilisers from cryo-EM structures. J Mol Biol 2017; 429: 633–46. doi: 10.1016/j.jmb.2017.01.001. PubMed
  4. Markman M. Managing taxane toxicities. Support Care Cancer 2003; 11: 144–7. doi: 10.1007/s00520-002-0405-9. PubMed
  5. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358: 1663–71. doi: 10.1056/NEJMoa0707056. PubMed
  6. Marks DH, Qureshi A, Friedman A. Evaluation of Prevention Interventions for Taxane-Induced Dermatologic Adverse Events: A Systematic Review. JAMA Dermatol 2018; 154: 1465–72. doi: 10.1001/jamadermatol.2018.3465. PubMed
  7. Zimmerman GC, Keeling JH, Burris HA, et al. Acute cutaneous reactions to docetaxel, a new chemotherapeutic agent. Arch Dermatol 1995; 131: 202–6. PubMed
  8. Minisini AM, Tosti A, Sobrero AF, et al. Taxane-induced nail changes: incidence, clinical presentation and outcome. Ann Oncol 2003; 14: 333–7. doi: 10.1093/annonc/mdg050. PubMed
  9. Sibaud V, Robert C, Mateus C, et al. Nail toxicities induced by systemic anticancer agents. Lancet Oncol 2015; 16: e181–9. doi: 10.1016/S1470-2045(14)71133-7. PubMed
  10. Re-visiting Hypersensitivity Reactions to Taxanes: A Comprehensive Review. Clin Rev Allergy Immunol 2015; 49: 177–91. doi: 10.1007/s12016-014-8416-0. PubMed
  11. Marchetti MA, Noland MM, Dillon PM, et al. Taxane associated subacute cutaneous lupus erythematosus 2013; 19: 192–59. PubMed
  12. Farrant PB, Mortimer PS, Gore M. Scleroderma and the taxanes. Is there really a link? Clin Exp Dermatol 2004; 29: 360–2. doi: 10.1111/j.1365-2230.2004.01519.x. PubMed
  13. Aydogan I, Kavak A, Parlak AH, et al. Persistent serpentine supravenous hyperpigmented eruption associated with docetaxel. J Eur Acad Dermatol Venereol 2005; 19: 345–7. doi: 10.1111/j.1468-3083.2005.01088.x. PubMed

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