Table 2. Prospective Clinical Trials in Advanced Squamous Cell Carcinoma of the Skin.

	Phase	Completion Date	Results
Chemotherapy Trials
Prospective observational study of cisplatin, 5-fluorouracil, and bleomycin in pretreated SCCS (n = 14)³⁵	II	1990	Four CR (30%), seven PR (54%). Local control after definitive XRT and/or surgery achieved in seven patients.
Prospective observational study of cisplatin and doxorubicin (n = 12)³⁵	III	1990	Four CR (33%), three PR (25%), 42% with progressive disease at time of report, both treated and untreated patients included
13-cis-retinoic acid and IFN alpha-2a: effective combination therapy for advanced SCCS (n = 32)³⁴	II	1992	28 evaluable; seven CR (25%), 12 PR (43%), 5-mo response duration
Oral 5-fluorouracil in SCCS (n = 14, pretreated patients)³⁵	II	2000	Therapy-induced measurable improvement in nine patients (64.3%): two PR, three minimal remissions, and four arrests of disease with median duration of 30+ months
Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced SCCS³⁶	II	2002	Six CR (17%), six PR (17%), median survival 14.6 mo, 67% RR in locally advanced and 17% RR in metastatic disease
Targeted Therapy Trials
Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable SCCS⁴² (n = 36)	II	2011	Disease control rate at 6 wk in 69% of pts (both locally advanced and metastatic). Best responses were eight partial responses and 2 CRs. No cetuximab-related deaths. Three related serious adverse events: two grade 4 infusion reactions and one grade 3 interstitial pneumopathy. Grades 1–2 acne-like rash occurred in 78% of patients and was associated with prolonged PFS. EGFR expression required for study entry.
A phase II study of gefitinib for aggressive SCCS of the head and neck (n = 23)⁴⁵	II	2011	Neoadjuvant approach followed by surgery or radiation; tolerable side effect profile; all patients received planned definitive treatment; 18% CR rate; Two-year OS 72.1%, PFS 63.6%. No EGFR mutations in 10 patients studied. Results led to a trial of erlotinib in this setting.
Phase 1 study of erlotinib plus radiation therapy in patients with advanced SCCS (n = 15)³³	I	2012	Treatment was felt to be tolerable. Most common toxicity attributed to erlotinib was grades 2–3 dermatologic reaction in 100% of patients, followed by mucositis (87%), and diarrhea (20%). Two-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 mo. Two-year OS was 65%, and DFS was 60%.
Ongoing Trials
Sirolimus in Kidney Transplant Patients With New or Recurrent SCCS Currently on Calcineurin-based Immunosuppression	II	Anticipated Dec-14	n/a
Study of Erlotinib in the Treatment of Recurrent or Metastatic SCCS	II	Anticipated Mar-15	n/a
Capecitabine in Treating Patients With Advanced or Recurrent SCCS	II	Anticipated Mar-16	n/a

Abbreviations: SCCS, squamous cell carcinoma of the skin; CR, complete response; PR, partial response; mo, months; RR, relative risk; pts, patients; PFS, progression-free survival; OS, overall survival; DFS, disease-free survival.