Docetaxel chemotherapy induces transverse superficial loss of the nail plate

Llombart-Cussac, A.

doi:10.1001/archderm.133.11.1466

Cited by 7 publications

(5 citation statements)

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“…Other systemic toxicities include cardiac arrhythmias, alopecia, mucositis, and fatigue (20). Skin and nail toxicities such as onycholysis, dermatitis, and reactive erythema (27,28) and cardiac conduction disturbances (29) are among other side effects resulting from the toxicities of this drug. Research on the design and development of water-soluble and tumor-specific taxane drugs, which could be formulated without the use of allergenic excipients and possess higher therapeutic indices without increasing the effective dose, is therefore well justified.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Paclitaxel−C225 Conjugate as a Model for Targeted Drug Delivery¹

et al. 2003

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Tumor-targeted drug delivery is an attractive strategy in cancer treatment. We have previously reported a paclitaxel model conjugate using a bombesin receptor-recognizing peptide in which the drug cytotoxicity against H1299 human nonsmall cell lung cancer was enhanced compared to unconjugated taxol. In an effort to expand the development of tumor-recognizing taxanes, paclitaxel (PTX, taxol) was conjugated to the anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MAb) Erbitux (C225) to serve as a model MAb-mediated drug delivery compound. Thus, paclitaxel was derivatized at its 2'-hydroxy function by introduction of a succinate linker, and the carboxyl group of the latter was covalently attached to C225 through amide bond formation. The final product conjugate (PTXC225) was analyzed mass spectrometrically for assessment of the drug-to-antibody ratios. Cytotoxicity screening of the drug-antibody conjugate against A431, UM-SCC-1, and UM-SCC-6 cells indicated an enhancement in cytocidal effect of paclitaxel as compared to those of the free drug, the intact antibody, and a physical mixture of the two (the controls). In A431 cells, the conjugate showed 25.2% +/- 2.2% of apoptosis induction as compared to little or no apoptosis caused by the controls. Biodistribution analysis of the PTXC225 in tumor-implanted nude mice and a tyrosine-kinase assay showed that conjugation of the drug did not interfere with the immunoreactivity of the antibody. The 24-h tumor uptake of C225 and PTXC225 were 11.7% +/- 6.0% and 7.1% +/- 3.6% of the injected dose per gram of tissue (%ID/g), respectively, which were not significantly different. Also, in A431-implanted nude mice, the conjugate and C225 showed tumor growth inhibition effects of 57.2% and 41.2%, respectively, against a saline-treated control, which were not significantly different from each other. This lack of difference in the in vivo antitumor activity of the MAb-delivered drug and free PTX may be due to either a relatively low dose of the antibody-delivered drug (346 microg/kg), or an untimely release of it, or both. The tumor growth inhibition pattern of the conjugate, however, was identical to that of C225, indicating that the attachment of PTX did not affect the antigen-binding and growth inhibitory features of the MAb. These preliminary results demonstrate the potential of tumor-targeted delivery of taxol as a promising strategy in cancer treatment and warrant further work to develop more suitable drug-MAb linkers as well as improved dosage and treatment protocols.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Paclitaxel−C225 Conjugate as a Model for Targeted Drug Delivery¹

et al. 2003

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“…Cutaneous and nail toxicities are the most frequent adverse reactions, following myelosuppression. Subungual haemorrhages, orange‐brown discoloration, onycholysis, Beau's lines, acute paronychia, subungual abscess and transverse loss of the nail plate have been described 3 . We present a case of docetaxel‐induced onychophosis, onycholysis, haemosiderin‐like nail bed discoloration and subungual abscess.…”

Section: Introductionmentioning

confidence: 92%

Docetaxel‐induced nail dystrophy

Nicolopoulos

Howard

2002

Aust J Dermatology

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A 73-year-old man with metastatic prostate cancer treated with weekly docetaxel chemotherapy for 5 months developed an acute nail dystrophy restricted to the fingernails. This was characterized by onycholysis, subungual haemorrhage and acute paronychia, progressing to a subungual abscess of the right index finger. Nail bed hyperaemia and haemosiderin-like nail bed discoloration were present. Nail plate avulsion was performed to decompress the acutely painful subungual abscess. The right thumb, middle finger and left index finger demonstrated early, proximal white subungual collections of pus obscuring the lunula (onychophosis). Central nail plate fenestrations with a surgical drill led to exudation of purulent material. Cultures of the subungual abscess material yielded mixed organisms, possibly related to administration of flucloxacillin for 1 week prior to presentation. The patient completed a further two courses of docetaxel without sequelae, and the nail dystrophy appears to be resolving. Docetaxel-induced nail changes are a common adverse effect, occurring in 30-40% of patients. Mild changes do not usually warrant the discontinuation of treatment.

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“…30,[31][32][33][34][35][36][37][38][39][40][41][42][43][44] This includes 3-weekly cycles, 30,[31][32][33][34][35][36][37][38][39][40]45,46 weekly cycles, 30,[41][42][43]45,46 and undefined schedules of administration. 44 Although docetaxel was deemed the likely causative agent, cases were reported using combination therapy with cisplatin, 31,37,45 carboplatin, 36 epirubicin, 36 capecitabine, 38 and trastuzumab. 40 Changes, including erythema, thinning, partial shedding, ridging, and hemorrhage between nail plates, were reported in initial studies using 3-weekly cycles.…”

Section: Docetaxelmentioning

confidence: 99%

Nail Toxicity Induced by Cancer Chemotherapy

Gilbar

Hain

Peereboom

2009

J Oncol Pharm Pract

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Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs.

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Docetaxel chemotherapy induces transverse superficial loss of the nail plate

Cited by 7 publications

References 0 publications

Synthesis and Biological Evaluation of Paclitaxel−C225 Conjugate as a Model for Targeted Drug Delivery¹

Synthesis and Biological Evaluation of Paclitaxel−C225 Conjugate as a Model for Targeted Drug Delivery¹

Docetaxel‐induced nail dystrophy

Nail Toxicity Induced by Cancer Chemotherapy

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Docetaxel chemotherapy induces transverse superficial loss of the nail plate

Cited by 7 publications

References 0 publications

Synthesis and Biological Evaluation of Paclitaxel−C225 Conjugate as a Model for Targeted Drug Delivery1

Synthesis and Biological Evaluation of Paclitaxel−C225 Conjugate as a Model for Targeted Drug Delivery1

Docetaxel‐induced nail dystrophy

Nail Toxicity Induced by Cancer Chemotherapy

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Synthesis and Biological Evaluation of Paclitaxel−C225 Conjugate as a Model for Targeted Drug Delivery¹

Synthesis and Biological Evaluation of Paclitaxel−C225 Conjugate as a Model for Targeted Drug Delivery¹