Begoña GRAÑA-SUÁREZ1Xavier HERNANDEZ-YAGÜE1
Xeroderma pigmentosum is a genodermatosis characterized by defects
in the DNA nucleotide excision repair pathway, which increases the
Hospital Josep Trueta,AV Francia s/n 17007 Girona. Spain
risk of suffering skin cancers. There is lack of information about the
efficacy and toxicity of chemotherapy and radiotherapy in the treat-
ment of these patients. We present the case of a xeroderma pigmento-
sum patient with a neck node recurrence of a squamous cell skin
carcinoma that achieved a good response and survival with cetuximab.
Key words: cetuximab, skin cancer, squamous cell carcinoma,
Reprints: J.R. Casadevall<[email protected]
>Article accepted on 7/10/2008
X erodermapigmentosum(XP)isarareautosomal tion chemotherapy followed by radiation and/or surgery,
defects in the DNA nucleotide excision repair
Although the effect of loss of the NER pathway on the
(NER) pathway. Patients are at an increased risk of suffer-
response to therapeutic agents is not well known, we
ing skin cancers in sun-exposed sites, due to faulty repair
decided to use the schema: cisplatin 50 mg per m2 day 1,
of ultraviolet light damage to DNA [1, 2]. We present a
and 5-fluorouracil 1000 mg per m2 days 1-3, every two
patient with XP diagnosed as having a primary squamous
weeks, in order to avoid toxicity. After four cycles we
cell skin carcinoma, spread to a neck node. The tumour
stopped chemotherapy due to delayed grade 3 thrombo-
was treated with chemotherapy, radiotherapy and, ulti-
cytopenia and lack of objective response.
Three months after the initial consultation the patientbegan radiotherapy, receiving a total dose of 50 Gy. Themetastatic neck node decreased in diameter by more than
50%, achieving a partial response without any relevantacute radiation side effect. Chemotherapy was continuedwith weekly vinorelbine, which was stopped because of
A 37-year-old man presented for evaluation of a level II,
refractory grade 2 leukopenia after 8 weeks of treatment.
fixed, growing, cervical node. He had been clinically
The patient progressed only locally six months after the
diagnosed with xeroderma pigmentosum early in his
end of radiotherapy (figure 1A). A new TC excluded dis-
infancy. His face showed multiple teleangiectases as
tant metastases. Cetuximab was then started at a load dose
well as atrophy and spotty hypopigmentations. He showed
of 400 mg per m2 continuing with 250 mg per m2 every
loss of vision due to clouding of the corneas. No relevant
week. Immunohistochemical staining for the EGF recep-
neurological abnormality had ever been reported. Several
tor was not performed. After 12 weeks of treatment, the
squamous and basal cell carcinomas had been surgically
cutaneous fistula closed definitively, the patient decreased
removed since he was an adolescent. Three months before
the use of analgesia and he improved his quality of life. At
consultation, a squamous cell carcinoma of his outer left
this time, the node experienced a good clinical response
ear was completely excised. A computed tomographic
(figure 1B) and almost a 50% diameter reduction mea-
scanning (CT) and a magnetic resonance imaging of the
sured by computed tomography and magnetic resonance.
neck revealed a left 60 by 30 mm node with a cutaneous
After eleven months of treatment with weekly cetuximab,
fistula. The node infiltrated the sternocleidomastoid mus-
patient suffered neck node enlargement and jaw bone
cle and involved neck vascular structures. A fine needle
infiltration. He was referred to palliative care, dying two
aspiration of the node was performed, which confirmed
years after his initial consultation.
the diagnosis of squamous cell carcinoma. Neither otolar-
The patient was referred for genetic counselling before
yngology endoscopies nor radiology image techniques
dying. He had an older sister also affected by xeroderma
revealed a new primary site. Therefore, he was diagnosed
pigmentosum, who suffered from melanoma, a carcinoma
as suffering an N3 node recurrence of a primary skin car-
of the lower lip, several squamous cell skin carcinomas
cinoma. Pre-treatment evaluation by a multidisciplinary
and blindness. The pedigree shown consanguinity, the
team dismissed surgery. It was decided to start with induc-
xeroderma pigmentosum cases in the family resulted
Xeroderma pigmentosum is characterized by a more than1000-fold increase in the frequency of all types of majorskin cancers (basal cell cancers, squamous cell cancers,malignant melanoma) in areas exposed to sunlight, com-pared to the normal population. The age of onset of thefirst skin cancers is 8 years-old . The worldwide inci-dence of XP is 1: 250,000 live births, usually presentingat age 1-2 years with photosensitivity and burning afterminimal sun exposure. Cutaneous manifestations alsoinclude increasing dryness of skin, freckling, and telangi-ectasia. Ocular abnormalities include photophobia, ectro-pion, conjunctival injection, keratitis, and tumours. About20-30% of patients with XP also have neurological abnor-malities. XP patients may also be at increased risk for thedevelopment of internal neoplasias (brain tumors, sarco-
mas, leukaemia and lung cancers). Although heterozy-gotes (carriers) are asymptomatic, it is unknown whetherthey have a higher risk of developing cancer comparing tonormal population .
Patients affected by XP should be referred for geneticcounselling and regular follow up by a multidisplinarymedical team early in life. Support and information forXP patients and their families is invaluable in order tohelp them to understand the condition and improve theprognosis and quality of life of these individuals .
The goal of treatment of xeroderma pigmentosum is tomake an early diagnosis and to protect the patient fromsunlight as there is no cure for this disease. Currently,there is a lack of information about the efficacy and safetyof conventional treatment in patients affected by XP andwith wide-spread cancer. The use of cisplatin in these
patients could both increase the expected toxicity and effi-cacy, as the XP cells are unable to repair DNA adducts
Figure 1. A) Before and B) after cetuximab
induced by this agent [6, 7]. T4 endonuclease liposomelotion  and oral retinoids like isotretinoin  have a
from marriage between cousins. The father had survived a
role in the chemo-prevention of skin cancer and have
Hodgkin disease diagnosed in his adolescence while the
also been used concomitantly with radiotherapy with
paternal grandfather died of lung cancer. Both our patient
and his sister refused any molecular genetic testing. After
Considering radiotherapy for XP patients, very few
our patient’s death, his sister blamed her parents for their
reports have been published and show conflicting out-
XP diagnosis and refused any follow up by medical and
comes: from no toxic events  to life-threatening side
effects before ending radiotherapy .
Cetuximab is a monoclonal antibody against the epider-mal growth factor receptor (EGFR). EGFR is commonly
overexpressed in squamous cell carcinomas of the headand neck and its genetic alterations are correlated withthe patient’s clinical outcome . According to the liter-
Xeroderma pigmentosum is an autosomal recessive
ature published at the time we treated our patient  and
photosensitive genodermatosis belonging to an expand-
recently,  when it is used in monotherapy it could
ing family of diseases with defects in the DNA nucleotide
achieve a response rate of 13% and a disease control
excision repair (NER) pathway. Patients have a genetic
rate of 46%. It has also shown activity with cisplatin in
inability to repair DNA damage induced by ultraviolet
refractory patients . Nowadays, cetuximab is accepted
light. There are two NER systems: 1) transcription-
as an option for first line treatment with concurrent radio-
coupled repair, and 2) global genome repair. Many fac-
theraphy for locally advanced head and neck cancer .
tors involved in these pathways are related to the patho-
In this case, a recurrent squamous cell skin carcinoma
genesis of XP . Genetically, xeroderma pigmentosum
diagnosed in an XP patient was treated with cetuximab
is a very heterogeneous disease that can be subdivided
as a monotherapy agent in a palliative setting. The use
into seven complementation groups (XPA through XPG)
of this targeted therapy facilitated a long stabilization of
and a XP Variant (XPV). Recently, the isolation and char-
the disease with very low toxicity. Cetuximab could be an
acterization of the genes responsible for XP have made it
acceptable treatment for XP patients affected with
possible to use molecular biological techniques to diag-
advanced squamous skin cell carcinomas. There are no
nose XP patients, for carrier detection and for prenatal
reports of the use of cetuximab concurrent with radiother-
Acknowledgements. Authors disclose no conflict of
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Wieder einmal scheint es sich zu bewahrheiten, dass der Herbst nicht gerade die Einige der von uns bereits genannten globa- einfachste Jahreszeit an der Börse ist. Die europäischen Märkte haben, beinahe len Konjunkturrisiken haben sich seit un- im Gleichschritt, allesamt seit den Höchstständen von Anfang Oktober an Terrain serer letzten «Aktien Schweiz»-Publikation verloren. E
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