Host-tumor relationships involve several factors that can enhance or suppress neoplastic growth. This second part of a review of basal cell carcinoma biology examines the role that hormones, cytokines, local and systemic immunity, congenital and genetic syndromes, and environmental factors play in the development of this neoplasm. Theories of etiology and pathogenesis are discussed, and transplantation and cell culture techniques used to study this cancer are explored. Valuable second-line therapies for treatment of multiple tumors are reviewed, and important areas of present and future research are emphasized.

Biology of basal cell carcinoma (Part I).

Nonmelanoma skin cancer is the leading cause of cancer in the United States. Cutaneous squamous cell carcinoma is second only to basal cell carcinoma in prevalence and its incidence is increasing. The biology of squamous cell carcinoma is reviewed under the broad areas of etiology, immunobiology, biochemistry, metastatic potential, and therapy, with emphasis on prevention, diagnosis, and management.

Biology of cutaneous squamous cell carcinoma

Basal cell carcinoma of the eyelid and periocular skin

The authors treated 14 patients with advanced squamous cell carcinoma (SCC) of the skin or lip with one to four cycles of combination chemotherapy consisting of cisplatin by bolus injection, and 5-fluorouracil (5-FU) and bleomycin by continuous 5-day infusion. Objective responses were seen in 11 of the 13 evaluable patients (84%). Four patients had a complete remission (30%) and seven patients, a partial remission (54%). Local control after definitive complementary radiation and/or surgical treatment was achieved in seven patients. Toxic side effects was acceptable; they consisted of nausea and vomiting in all patients, transient skin changes, hematologic (Grade 3/4) abnormalities in four patients, and pulmonary fibrosis in one elderly patient. These results show that this chemotherapy combination could play a role in reducing the tumor mass and in facilitating definitive treatment to obtain better functional and cosmetic results in advanced SCC of the skin.

Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin.

Purpose: To determine the disease control rate and toxicity of treating patients with aggressive cutaneous squamous cell carcinoma (CSCC) with neoadjuvant gefitinib. Experimental Design: A prospective phase II clinical trial evaluating neoadjuvant gefitinib given prior to standard treatment with surgery and/or radiotherapy. Patients with stable disease after one cycle received escalated doses. Patients who responded were given gefitinib during radiation therapy, as well as maintenance therapy after definitive treatment. We analyzed the correlation between epidermal growth factor receptor (EGFR) expression, mutation status, and gene copy number on available tissue samples and clinical response. Results: Twenty-three patients were accrued and 22 patients were evaluable for response prior to definitive local treatment; complete responses were attained by 18.2% of patients and partial responses by 27.3%. Grades 2 to 3 toxicities were observed in 59.1% of patients experiencing class-specific effects during induction therapy. After induction, 11.8% underwent surgery alone, 17.6% had definitive radiation, 11.8% were treated with radiation and concurrent gefitinib, and 47% had surgery with postoperative radiation and concurrent gefitinib. Median follow-up for the censored observations was 32 months. Two-year overall, disease-specific, and progression-free survival rates were 72.1%, 72.1%, and 63.6%, respectively. No EGFR-activating mutations were identified in tumor samples available from 10 patients. No associations between EGFR correlative studies and patient outcomes were identified. Conclusions: Gefitinib, in the neoadjuvant setting, was active and well tolerated in patients with aggressive CSCC and did not interfere with definitive treatment. In view of the 18% complete response rate we observed, EGFR tyrosine kinase inhibitors should be further explored in the treatment of aggressive CSCC. Clin Cancer Res; 18(5); 1435–46. ©2012 AACR .

https://clincancerres.aacrjournals.org/content/clincanres/18/5/1435.full.pdf

A Phase II Study of Gefitinib for Aggressive Cutaneous Squamous Cell Carcinoma of the Head and Neck

Eleven patients with advanced basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin were treated with cis-diamminedichloroplatinum II (cisplatin) and doxorubicin. Seven patients had prior surgery and six of these seven had prior radiation therapy. All patients had an adequate trial of chemotherapy. One patient received a second course of chemotherapy after relapse. Responses were seen in 10 of 12 (87%) of chemotherapy courses, and 5 of 11 patients (46%) have an unmaintained complete remission lasting 2 to 31 months. Toxicity was acceptable and consisted primarily of gastrointestinal side effects. These results indicate the combination of cisplatin and doxorubicin has significant activity in both advanced BCC and SCC of the skin. In addition, a portion of patients treated with the combination achieve a long-term unmaintained disease-free state.

Cisplatin and doxorubicin. An effective chemotherapy combination in the treatment of advanced basal cell and squamous carcinoma of the skin.

The morbidity from juvenile laryngeal papillomatosis (JLP), a disease process characterized by recurrent growth of multiple epithelial papillomas, has greatly improved with the advent of immunomodulating agents used in combination with the surgical approach of CO2 laser vaporization. In prospectively evaluating the immunologic status of four pediatric patients with this disorder, one patient repeatedly demonstrated IgG2 subclass deficiency. One of two children found to have subnormal functional natural killer (NK) activity received thrice weekly intramuscular administration of 3,000,000 units/m2 body surface area of human leukocyte (alpha) interferon (IFN). Natural killer function normalized, but therapy was discontinued after 4 months; however, no clinical benefits from IFN administration were observed. Further in vitro evaluation of NK function and lymphokine production is needed, in order eventually to offer more effective immunomodulating agents to such patients. A brief review of the literature concerning JLP is also presented.

John D. Harmon

Papers

Cisplatin and doxorubicin. An effective chemotherapy combination in the treatment of advanced basal cell and squamous carcinoma of the skin.

Evaluation of immunocompetency in juvenile laryngeal papillomatosis.

Head and neck and plastic surgery: staining of surgical specimens with toluidine blue prior to frozen section examination