Gefitinib and PEG-Interferon Alfa-2a in Treating Patients With Unresectable or Metastatic Skin Cancer

A Phase I/II Pilot Study of Bioimmunotherapy With IRESSA (Gefitinib) and Pegylated Interferon Alpha-2a for Patients With Unresectable/Metastatic Squamous Cell Carcinoma of the Skin

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PEG-interferon alfa-2a may interfere with the growth of tumor cells and slow the growth of skin cancer. Giving gefitinib together with PEG-interferon alfa-2a may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of PEG-interferon alfa-2a when given together with gefitinib and to see how well they work in treating patients with unresectable or metastatic skin cancer.

OBJECTIVES:

• Determine the tolerability of gefitinib and PEG-interferon alfa-2a in patients with unresectable or metastatic squamous cell carcinoma of the skin.
• Determine the response rate in patients treated with gefitinib for 1 month.
• Determine whether the addition of weekly PEG-interferon alfa-2a to ongoing gefitinib improves response rate in these patients .
• Determine whether PEG-interferon alfa-2a exacerbates rash in patients who have been treated with gefitinib for 1 month.

OUTLINE: This is a phase I, pilot, dose de-escalation study of PEG-interferon alfa-2a followed by an open-label, phase II study.

• Phase I: Patients receive oral gefitinib alone once daily for 4 weeks. Beginning in week 5, patients also receive PEG-interferon alfa-2a subcutaneously once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of patients receive de-escalating doses of PEG-interferon alfa-2a until a tolerable dose is determined.

• Phase II: Patients receive gefitinib and PEG-interferon alfa-2a at the tolerable dose determined in phase I.

PROJECTED ACCRUAL: A total of 16 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary squamous cell carcinoma of the skin

  • Metastatic and/or unresectable locally recurrent disease

• Measurable disease

• No curative treatment option (including resection and radiotherapy) exists or is unacceptably morbid

PATIENT CHARACTERISTICS:

• WHO performance status 0-2

• Absolute neutrophil count > 1,500/mm³

• Platelet count > 100,000/mm³

• Bilirubin < 1.5 times upper limit of normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• HIV/AIDS allowed

• Patients with other cancer diagnoses (e.g., chronic lymphocytic leukemia) are eligible provided disease is controlled and does not require active treatment

• No pre-existing medical problems or laboratory abnormalities ≥ grade 3 except renal allograft patients with chronic, stable grade 3-4 renal insufficiency who are dialysis candidates

  • Nontransplant patients with any degree of renal insufficiency allowed

• No serious medical or psychiatric illness that would preclude study compliance

• No evidence of severe or uncontrolled (≥ grade 3) systemic disease (e.g., unstable or uncompensated respiratory, cardiac, or hepatic disease)

PRIOR CONCURRENT THERAPY:

• Prior solid organ transplant allowed
• Prior cytotoxic chemotherapy and radiotherapy allowed
• More than 30 days since prior experimental cancer treatment
• No prior epidermal growth factor receptor-inhibiting drugs, including gefitinib, erlotinib hydrochloride, or cetuximab
• No concurrent radiotherapy
• No concurrent cytotoxic chemotherapy or other drugs intended to control skin cancer