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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.


Taxanes — codes and concepts
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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 yew trees.

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

How do taxanes work?

Taxanes are antineoplastic drugs that 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 [2].

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 [2,3]:

  • Fatigue
  • Body aches
  • Loss of appetite.

Other adverse effects include [2,3]:

  • 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 [2,4].

Adverse cutaneous effects of chemotherapy
 

Hair loss from taxanes

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

  • 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.
  • Scalp cooling systems such as cool caps have been shown to prevent the alopecia in a number of trials [4].

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 [2,5]:

  • Hyperpigmentation (diffuse melanonychia)
  • Koilonychia
  • Nail ridging and fissures
  • Beau lines
  • Periungual tissue formation
  • Haemorrhagic onycholysis and subungual haematoma/abscess appear to be unique to the taxanes.

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

Skin cooling systems such as frozen gloves have been shown to reduce the adverse effects on the nails [4]. Avoidance of trauma to the hands and nails, and the use of hand moisturisers are recommended. The use of nail lacquer also seems to be helpful, suggesting photo-sensitivity may play a role in the development of some of the nail effects [6].

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 [2,7].

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].
  • The use of frozen gloves has been reported to reduce this reaction [4].

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 [2,8].

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 [9].

Recall inflammatory reactions

  • Radiation recall, UV recall, and extravasation recall dermatitis due to taxanes have been reported.
  • Radiation and UV recall is characterised by erythema, swelling, and skin breakdown at the site of previous radiotherapy or recent sunburn [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 [10].

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(8932):1267-72. doi:10.1016/s0140-6736(94)90754-4. PubMed
  2. Sibaud V, Lebœuf NR, Roche H, et al. Dermatological adverse events with taxane chemotherapy. Eur J Dermatol. 2016;26(5):427-43. doi:10.1684/ejd.2016.2833. Journal
  3. Markman M. Managing taxane toxicities. Support Care Cancer. 2003;11(3):144-7. doi:10.1007/s00520-002-0405-9. PubMed
  4. Marks DH, Qureshi A, Friedman A. Evaluation of prevention interventions for taxane-induced dermatologic adverse events: a systematic review. JAMA Dermatol. 2018;154(12):1465-72. doi:10.1001/jamadermatol.2018.3465. PubMed
  5. Robert C, Sibaud V, Mateus C, et al. Nail toxicities induced by systemic anticancer treatments. Lancet Oncol. 2015;16(4):e181-9. doi:10.1016/S1470-2045(14)71133-7. PubMed
  6. Alshari O, Aleshawi A, Al Sharie AH, et al. The effect of nail lacquer on taxane-induced nail changes in women with breast cancer. Breast Cancer (Auckl). 2020;14:1178223420929702. doi:10.1177/1178223420929702. PubMed
  7. Picard M, Castells MC. Re-visiting hypersensitivity reactions to taxanes: a comprehensive review. Clin Rev Allergy Immunol. 2015;49(2):177-91. doi:10.1007/s12016-014-8416-0. PubMed
  8. Marchetti MA, Noland MM, Dillon PM, et al. Taxane associated subacute cutaneous lupus erythematosus 2013; 19: 192–59. PubMed
  9. Farrant PB, Mortimer PS, Gore M. Scleroderma and the taxanes. Is there really a link?. Clin Exp Dermatol. 2004;29(4):360-362. doi:10.1111/j.1365-2230.2004.01519.x. PubMed
  10. Aydogan I, Kavak A, Parlak AH, Alper M, Annakkaya AN, Erbas M. Persistent serpentine supravenous hyperpigmented eruption associated with docetaxel. J Eur Acad Dermatol Venereol. 2005;19(3):345-7. doi:10.1111/j.1468-3083.2005.01088.x. PubMed

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