CASE REPORT Russell B. Smith, MD, Section Editor

CETUXIMAB AS PRIMARY TREATMENT FOR CUTANEOUSSQUAMOUS CELL CARCINOMA TO THE NECK

Sung Kim, MD,1 Michael Eleff, MD,2 Nicos Nicolaou, MD3

1Radiation Oncology, Cancer Institute of New Jersey, New Brunswick, New Jersey. E-mail: kim18@umdnj.edu2Medical Oncology, Cancer Institute of New Jersey, Hamilton, New Jersey3Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Accepted 14 September 2009Published online 1 December 2009 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/hed.21299

Abstract: Background. Head and neck cutaneous squa-

mous cell carcinoma (SCC) metastatic to lymph nodes is com-

monly treated with surgery plus radiotherapy.

Methods. We present the case of a 92-year-old man with

cutaneous SCC metastatic to the neck (7 cm) who was treated

with primary cetuximab and has had a durable complete

response for 7 months. Because of his age, comorbidities, and

unresectable neck lymphadenopathy, he received primary

cetuximab. He received a 400 mg/m2 loading dose and a 250

mg/m2 weekly dose for 3 months and then had to discontinue

as a result of other unrelated medical issues.

Results. The patient had a complete response by 6 weeks.

Seven months after discontinuing cetuximab, he continues to

have a complete response.

Conclusions. Primary cetuximab for cutaneous SCC meta-

static to lymph nodes is an area that bears further investigation

because of its apparent efficacy and excellent toxicity

profile. VVC 2009 Wiley Periodicals, Inc. Head Neck 33: 286–

288, 2011

Keywords: cutaneous; squamous cell carcinoma; SCC;

metastatic; cetuximab

Fortunately, only a small minority (2% to 3%) of headand neck cutaneous squamous cell carcinomas (SCCs)will metastasize to lymph nodes (most commonly theparotid lymph nodes). However, when metastases dooccur, they can require extensive and toxic treatment.In the United States, about 2500 patients will dieannually as a result of advanced cutaneous SCC.

The most efficacious treatment is surgical resec-tion followed by radiation therapy. This approachdecreases the risk of locoregional recurrence toroughly 20% to 25%, whereas single-modality treat-ment (surgery or radiation alone) is associated with a>50% chance of locoregional recurrence.1 However,this combined-modality approach can be very toxicand, in some cases, the patient may not be a com-bined-modality candidate. Here we present a case of

an elderly patient with unresectable neck metastaseswho was treated with primary cetuximab (Erbitux,Bristol-Myers Squibb, New York, NY), with a durablecomplete response.

CASE REPORT

The patient was a 92-year-old white man witha history of coronary artery disease status post (S/P)pacemaker, prostate adenocarcinoma treated with pri-mary hormonal therapy with durable biochemicalresponse, early rectosigmoid adenocarcinoma success-fully treated with resection alone, and chronic lym-phocytic leukemia that had never required treatment.He had a history of a forehead skin lesion excised inApril 2008 and a right posterior auricular skin lesionexcised in May 2008. Pathology for both lesions waspoorly differentiated SCC with positive margins. Atthe time of the second surgery, he noticed a smallright neck mass, which then grew rapidly over thenext month to >7 cm in size (Figure 1). The neckmass was biopsied and found to be SCC. There wasno evidence of recurrence at the forehead or auricularprimary sites. Clinical head and neck examination ofthe oral cavity/oropharynx and PET/CT scan revealedno other primary tumor, so the neck metastases werethought to have originated from 1 of his skin SCCs.The PET/CT scan in fact revealed intense uptake inthe right neck, as expected, but also revealed uptakein a smaller contralateral neck lymph node. He saw ahead and neck surgeon, who deemed the neck massunresectable because of involvement of the right ca-rotid artery (Figure 2). He was then referred for radi-ation therapy.

Because of the large size and bilaterality of theneck metastases, anticipated radiation toxicity wouldhave included fatigue, skin desquamation and pain,significant mucositis and weight loss, xerostomia, andchange in taste. Considering his age and comorbid-ities, this would have been a very difficult treatmentfor him, and it was decided to try a course of cetuxi-mab prior to radiation. He received a 400 mg/m2

Correspondence to: S. KimVVC 2009 Wiley Periodicals, Inc.

286 Cetuximab as Primary Treatment for Cutaneous SCC to Neck HEAD & NECK—DOI 10.1002/hed February 2011

loading dose and a 250 mg/m2 weekly dose for 3months. The patient was agreeable to have his his-tory and images presented in this case report.

There was a clear difference in the size and con-sistency of the neck mass after 1 week, and he had acomplete response by 6 weeks (Figure 3). The patientstarted cetuximab at the end of July 2008 and contin-ued weekly treatment until early October 2008. Atthat point, he suffered multiple other medical set-backs, including small bowel obstruction, fall andright hip fracture, and deep venous thrombosis. Hewent to a nursing facility and underwent rehabilita-tion, and has not received cetuximab since October2008. We last saw him in follow-up in early June2009, and he was clinically without evidence of recur-rence at the primary sites or at the neck (Figure 4).

DISCUSSION

Cetuximab is a monoclonal antibody against epider-mal growth factor receptor (EGFR). There certainly isgreat precedent for the activity of cetuximab againstSCC. Bonner et al2 performed a randomized con-trolled trial of radiation þ cetuximab versus radiationalone for head and neck SCCs (cutaneous SCCs wereexcluded), and demonstrated improvement in bothprogression-free and overall survival in the cetuximabarm. In the setting of recurrent or metastatic headand neck SCC, Vermorken et al3 demonstrated thatthe addition of cetuximab to platinum-based chemo-therapy significantly improved both progression-freeand overall survival.3 Evidence for primary cetuximabfor advanced head and neck SCC is lacking. Thereare some clinical data for cetuximab as a primarytreatment for advanced cutaneous SCC. Bauman andcolleagues4 reported 2 cases of recurrent (after pri-mary surgery and radiation), in-transit cutaneousSCC in elderly patients. Both were treated withcetuximab, 1 having a complete response by week 16

FIGURE 2. CT prior to cetuximab.

FIGURE 1. Prior to cetuximab. FIGURE 3. Six weeks after starting cetuximab.

FIGURE 4. Seven months after stopping cetuximab.

Cetuximab as Primary Treatment for Cutaneous SCC to Neck HEAD & NECK—DOI 10.1002/hed February 2011 287

and the other a nearly complete response by week 12.

As in our patient, cetuximab was well tolerated with

the exception of acneiform skin rash. It is likely that

cetuximab may be effective in only selected patients

with advanced cutaneous SCC. Fogarty et al5 looked

at 21 cases of mostly advanced cutaneous SCC, and

found that only 9 (43%) demonstrated EGFR expres-

sion above background; of these cases, only 5

expressed phosphorylated (activated) EGFR. In con-

clusion, primary cetuximab for selected patients with

advanced cutaneous SCC bears further investigation

because of its possible efficacy and excellent toxicity

profile.

REFERENCES

1. Veness MJ, Porceddu S, Palme CE, et al. Cutaneous head andneck squamous cell carcinoma metastatic to parotid and cervicallymph nodes. Head Neck 2007;29:621–631.

2. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuxi-mab for squamous-cell carcinoma of the head and neck. N Engl JMed 2006;354:567–578.

3. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemo-therapy plus cetuximab in head and neck cancer. N Engl J Med2008;359:1116–1127.

4. Bauman JE, Eaton KD, Martins RG. Treatment of recurrentsquamous cell carcinoma of the skin with cetuximab. Arch Der-matol 2007;143:889–892.

5. Fogarty GB, Conus NM, Chu J, et al. Characterization of theexpression and activation of the epidermal growth factor receptorin squamous cell carcinoma of the skin. Br J Dermatol2007;156:92–98.

288 Cetuximab as Primary Treatment for Cutaneous SCC to Neck HEAD & NECK—DOI 10.1002/hed February 2011