Skin toxicity in cancer treatment: what the evidence shows about prevention and management
- Vitor Pratte
- 7 hours ago
- 9 min read
Skin toxicity is a frequent complication of cancer treatment, and to a large extent a predictable and treatable one. Its frequency depends above all on the drug class: with EGFR inhibitors, acneiform rash is the most common cutaneous toxicity and occurs in up to 90% of patients exposed (Apalla et al., 2025), while in targeted therapies and immunotherapy for melanoma clinical series describe figures in the order of 30 to 50%. Recognising it early, grading it correctly and treating it in a targeted way is what allows cancer treatment to continue.
This article brings together the key clinical points from the Pierre Fabre clinical session in which Dr. Ellene Papazis, a dermatologist at the Instituto Português de Oncologia do Porto (IPO-Porto), was an invited speaker, held on 14 March 2026, between 10:00 and 12:00, at Timbre Heroísmo in Porto. It had a practical, interactive format, with discussion of real clinical cases. It was aimed at health professionals and formed part of the initiative Act For Skin, Care for Cancer Patients. Dr. Ellene Papazis's talk focused on the management of dermatological toxicity in the cancer patient: how to recognise it early, how to grade it and how to treat it without compromising antineoplastic treatment.
Updated on 25 July 2026. All data presented refer to the studies listed at the end.
Skin toxicity in cancer treatment: why the skin matters
The frequency and type of reaction vary with the drug class, and that distinction is clinically useful. The European ESMO guidelines systematise the prevention and treatment of dermatological toxicities precisely by drug class, because the profile is not the same (Lacouture et al., 2021). This is not a minor cosmetic problem: dermatological reactions affect quality of life, may force dose adjustments and, in more severe cases, interruption of treatment.
Assessment has to consider who the person in treatment is, including age group, phototype, pre-existing skin disease, comorbidities and occupational activity. The same drug does not have the same impact on a 40-year-old with healthy skin and on a 70-year-old with pre-existing psoriasis who works outdoors.
The most prevalent dermatological changes include xerosis, pruritus, dyschromia, photosensitivity, rash, alopecia and nail changes. Severity is graded by the CTCAE criteria (Common Terminology Criteria for Adverse Events), the standardised system used in oncology, which allows dermatology and oncology to align their language.
Acneiform rash and EGFR inhibitors
Acneiform rash, with papules and pustules typically on the face and upper trunk, is the most frequent cutaneous toxicity of epidermal growth factor receptor inhibitors (EGFRi) such as cetuximab, panitumumab, erlotinib and gefitinib.
In 2025 the first Europe/USA Delphi consensus on its clinical management was published, bringing together 32 oncodermatology specialists from Europe, the USA, Canada, Argentina, Asia and Israel, led by the Task Force Dermatology for Cancer Patients of the European Academy of Dermatology and Venereology (Apalla et al., 2025). Strong consensus was reached on 75 of the 84 statements assessed.
Among the recommendations that reached consensus:
Daily emollient and sun protection with SPF above 30 for all patients on EGFRi. This was the prophylactic measure with the highest level of agreement among the experts.
Avoid irritant products, including those containing salicylic acid and the retinoids commonly used in acne vulgaris.
Oral doxycycline (100 or 200 mg/day) as pre-emptive treatment, maintained for at least 6 weeks after starting the EGFRi.
Medium-potency topical corticosteroid on the trunk and extremities; low potency on the face and skin folds.
Do not use topical antibiotics, neither for prevention nor for treatment. This conclusion runs against a practice that is still common.
Low-dose oral isotretinoin only as second line, in refractory grade II/III cases or where tetracyclines are contraindicated.
Modify or discontinue the EGFRi only in potentially life-threatening situations or when quality of life is severely compromised, with the decision shared between patient, oncologist and dermatologist.
Hand-foot syndrome
Hand-foot syndrome (palmar-plantar erythrodysaesthesia) presents with palmar and plantar erythema and oedema, painful fissures and intense desquamation, frequently accompanied by dysaesthesia or paraesthesia and associated nail involvement.
For prevention, concrete measures were discussed: use of cooling gloves during chemotherapy, regular moisturising, avoiding excessive hand washing, avoiding false nails, avoiding tight shoes and situations of friction, and avoiding compulsive manipulation of the skin. For treatment: moisturising, medium- to high-potency topical corticosteroid, anti-inflammatories (celecoxib in the context of capecitabine) and topical anaesthetics.
Alopecia and nail changes
Hair loss is one of the aspects that most concerns patients during treatment and can influence adherence to therapy. It usually begins one to two weeks after the start of therapy and is complete within the first or second month. In most cases it is reversible, although the hair may return with changes in shape, colour and density. The degree of reversibility relates to damage to the matrix and to the follicular bulge, and irreversible alopecia has been described with taxanes. Distinguishing between scarring and non-scarring alopecia is therefore clinically decisive.
In the nail apparatus the spectrum is broad: onycholysis (distal, proximal or total), leukonychia, onychoschizia, trachyonychia, erythronychia and splinter haemorrhages, paronychia, pyogenic granuloma and chromonychia.
Prevention comes down to simple and sometimes neglected gestures: the correct way to cut the nail, not removing the cuticle, moisturising with petrolatum- or oil-based products. For treatment, depending on the picture: topical antibiotic, silver nitrate, trichloroacetic acid, timolol, cryotherapy and laser therapy.
BRAF/MEK targeted therapies in melanoma
Combinations of BRAF and MEK inhibitors have transformed the treatment of advanced melanoma, but they have a dermatological profile of their own. In an assessment of the tolerability of these combinations, photosensitivity was described in up to 34% of patients, particularly with vemurafenib; treatment interruption due to adverse effects occurred in around 11 to 16%; and secondary skin tumours appeared in approximately 2 to 7% of patients (Heinzerling et al., 2019). The full spectrum of cutaneous reactions to these drugs, and how to treat them without suspending therapy, is reviewed in detail by Mavropoulos and Wang (2014).
A counterintuitive and clinically relevant finding: adding the MEK inhibitor reduces the incidence of secondary skin tumours, because it blocks the paradoxical activation of the MAPK pathway caused by BRAF inhibition alone (Mavropoulos & Wang, 2014).
On the immunotherapy side, a prospective study conducted at the Oncological Dermatology Unit in Bologna, which followed patients with cutaneous melanoma treated with immune checkpoint inhibitors between January 2016 and April 2024, reinforces the same practical conclusion: cutaneous adverse events affect quality of life and, in severe cases, may force interruption or discontinuation of cancer therapy, which makes dermatological assessment decisive (Venturi et al., 2024).
When the skin is a sign that treatment is working
This was one of the most discussed points of the session. Cutaneous toxicity is not always simply collateral damage to be suppressed. In certain contexts it is a marker of therapeutic activity.
In a retrospective study of 62 patients with unresectable colorectal adenocarcinoma treated with cetuximab, those who developed early cutaneous toxicity had significantly longer overall survival, and those with higher grades of cutaneous toxicity had a longer time to disease progression (Kogawa et al., 2015).
The biological basis for this association has been demonstrated experimentally. Using a 3D microfluidic co-culture model linking, in the same circuit, spheroids of human lung tumour cells and a full-thickness human skin equivalent, it was possible to assess at the same time the antitumour effect and the adverse cutaneous effect of cetuximab. Repeated treatment increased the expression of pro-apoptotic genes in the tumour tissue and, in parallel, eliminated the proliferative keratinocytes of the basal layer of the skin (Hübner et al., 2018). The same mechanism, the same target, two tissues.
As Dr. Ellene Papazis summarised during the session: "In immunotherapy, the skin is sometimes not just a victim: it can be a witness to an effective immune response."
This does not mean tolerating avoidable suffering. It means that the decision to reduce the dose or suspend therapy because of the skin should be taken in the knowledge of what that reaction may also represent, and after supportive dermatological measures have been exhausted.
Radiotherapy and overlapping cases
Radiotherapy has its own spectrum of associated inflammatory dermatoses, which may arise in the irradiated area or at a distance, and whose differential diagnosis from drug-induced toxicoderma is not always evident (Hernández Aragüés et al., 2017).
The clinical cases discussed in the session illustrated exactly this difficulty: patients on multiple drugs, with concomitant radiotherapy and relevant comorbidities, in whom attributing the skin reaction to a single cause is frequently impossible, and in whom the therapeutic decision has to be taken all the same.
Why the dermatologist should come in early
This was the central argument of the presentation, and it has quantified support.
In a retrospective study conducted at Memorial Sloan Kettering Cancer Center, the involvement of dermatologists in outpatient consultations for cancer patients with acute dermatological adverse events was associated with better outcomes, less recurrence of cutaneous toxicity and a relevant reduction in interruption of antineoplastic therapy (Barrios et al., 2020).
There are now structured recommendations from expert panels for the management of dermatological adverse events of cancer therapies, which systematise the approach by drug class and by severity grade (Cury-Martins et al., 2020).
In the words of Dr. Ellene Papazis: "The dermatologist does not come in at the end; they come in early to keep the cancer treatment viable."
Closing message
Dermatological toxicity is a frequent, predictable and largely treatable complication of cancer treatment. Each type of therapy, whether chemotherapy, immunotherapy, radiotherapy or targeted therapies, has its own mechanisms of cutaneous toxicity and calls for distinct approaches.
Simple, consistent measures significantly reduce the impact of these effects: gentle cleansing, regular moisturising with an appropriate vehicle, sun protection, attention to the mucous membranes and nails, light cotton clothing and avoiding friction. And continuous monitoring makes it possible to identify toxicities early, preventing severe complications.
Multidisciplinary follow-up, involving oncologists, dermatologists, nursing and psychological support, is what makes it possible to optimise care and ensure continuity of treatment.
Related article
This was the second clinical session on cutaneous drug reactions led by Dr. Ellene Papazis. On the first, held in March 2025, read Cutaneous drug reactions in oncology: clinical session with Dr. Ellene Papazis in Porto.
Note: This article is for information and education purposes and is intended to disseminate the scientific content presented at a session aimed at health professionals. It does not replace individual medical assessment. If you are undergoing cancer treatment and have developed changes in your skin, nails or hair, speak to your treating team.
Oncological dermatology consultations with Dr. Ellene Papazis, in Porto (Boavista). Consultations in Portuguese, English and Spanish.
References
Apalla, Z., Freites-Martinez, A., Grafanaki, K., Ortiz-Brugues, A., Nikolaou, V., Fattore, D.,
Sollena, P., Deverapalli, S., Babakoohi, S., Galimont, A., Kluger, N., Beylot-Barry, M.,
Larocca, C., Iriarte, C., Smith, J., Tattersall, I., Dodiuk-Gad, R., Sauder, M., Carrera, C.,
Sibaud, V. (2025). Management of human epidermal growth factor receptor inhibitors-related acneiform rash: A position paper based on the first Europe/USA Delphi consensus process. Journal of the European Academy of Dermatology and Venereology, 39(4), 730-741. https://doi.org/10.1111/jdv.20391
Barrios, D. M., Phillips, G. S., Freites-Martinez, A., Hsu, M., Ciccolini, K., Skripnik Lucas, A., Marchetti, M. A., Rossi, A. M., Lee, E. H., Deng, L., Markova, A., Myskowski, P. L., &
Lacouture, M. E. (2020). Outpatient dermatology consultations for oncology patients with acute dermatologic adverse events impact anticancer therapy interruption: A retrospective study. Journal of the European Academy of Dermatology and Venereology, 34(6), 1340-1347. https://doi.org/10.1111/jdv.16159
Cury-Martins, J., Eris, A. P. M., Abdalla, C. M. Z., Silva, G. B., Moura, V. P. T., & Sanches, J.
A. (2020). Management of dermatologic adverse events from cancer therapies: Recommendations of an expert panel. Anais Brasileiros de Dermatologia, 95(2), 221-237. https://doi.org/10.1016/j.abd.2020.01.001
Heinzerling, L., Eigentler, T. K., Fluck, M., Hassel, J. C., Heller-Schenck, D., Leipe, J.,
Pauschinger, M., Vogel, A., Zimmer, L., & Gutzmer, R. (2019). Tolerability of BRAF/MEK inhibitor combinations: Adverse event evaluation and management. ESMO Open, 4(3), Article e000491. https://doi.org/10.1136/esmoopen-2019-000491
Hernández Aragüés, I., Pulido Pérez, A., & Suárez Fernández, R. (2017). Dermatosis inflamatorias asociadas a radioterapia. Actas Dermo-Sifiliográficas, 108(3), 209-220. https://doi.org/10.1016/j.ad.2016.09.019
Hübner, J., Raschke, M., Rütschle, I., Gräßle, S., Hasenberg, T., Schirrmann, K., Lorenz, A.,
Schnurre, S., Lauster, R., Maschmeyer, I., Steger-Hartmann, T., & Marx, U. (2018).
Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model. Scientific Reports, 8, Article 15010. https://doi.org/10.1038/s41598-018-33462-3
Kogawa, T., Doi, A., Shimokawa, M., Fouad, T. M., Osuga, T., Tamura, F., Mizushima, T.,
Kimura, T., Abe, S., Ihara, H., Kukitsu, T., Sumiyoshi, T., Yoshizaki, N., Hirayama, M., Sasaki,
T., Kawarada, Y., Kitashiro, S., Okushiba, S., Kondo, H., & Tsuji, Y. (2015). Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer. Targeted Oncology, 10(1), 125-133. https://doi.org/10.1007/s11523-014-0322-0
Lacouture, M. E., Sibaud, V., Gerber, P. A., van den Hurk, C., Fernández-Peñas, P., Santini, D., Jahn, F., & Jordan, K. (2021). Prevention and management of dermatological toxicities related to anticancer agents: ESMO clinical practice guidelines. Annals of Oncology, 32(2), 157-170. https://doi.org/10.1016/j.annonc.2020.11.005
Mavropoulos, J. C., & Wang, T. S. (2014). Managing the skin toxicities from new melanoma drugs. Current Treatment Options in Oncology, 15(2), 281-301. https://doi.org/10.1007/s11864-014-0284-6
Venturi, F., Veronesi, G., Scotti, B., & Dika, E. (2024). Cutaneous toxicities of advanced treatment for cutaneous melanoma: A prospective study from a single-center institution. Cancers, 16(21), Article 3679. https://doi.org/10.3390/cancers16213679
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