Phase II Study of Skin Toxicity Dosing of IRESSA (Gefitinib) in Squamous Cell Carcinoma of the Head and Neck
Phase II Study of Skin Toxicity Dosing of IRESSA (Gefitinib) in Squamous Cell Carcinoma of the Head and Neck
The purpose of this study is to demonstrate the activity (response rate and rate of stable
 disease) of Iressa administered as a single agent escalated to a dose that produces grade 2
 skin toxicity in patients with recurrent and/or metastatic squamous cell carcinoma of the
 head and neck (SCCHN).
This open-label, multi-institution, phase II study evaluated the activity of gefitinib at
 individually escalated doses up to 750mg to achieve the skin toxicity grade greater than or
 equal to 2. Patients were started on gefitinib 250mg orally daily for 2 weeks. At 2 weeks,
 patients were reevaluated and given skin toxicity grade according to the National Cancer
 Institute Common Toxicity Criteria version 3.0 (CTC 3.0). Patients with grade 2 or greater
 skin toxicity remained on 250 mg daily; in patients with grade 0-1 skin toxicity the dose was
 escalated to 500 mg daily and again to 750 mg daily on next evaluation until grade 2 or
 greater skin toxicity was developed.

 The protocol was later amended because of the reported lower efficacy of the 250 mg dose and
 patients were then started at 500 mg per day. There was no further dose escalation beyond 750
 mg per day irrespective of the response or grade of skin toxicity. Therapy was discontinued
 upon disease progression, unacceptable toxicity, death or patient's withdrawal of consent.
 Dose interruptions were used as the first approach to managing the toxicity of the patients
 who experienced grade 3-4 non-hematological toxicities. Gefitinib was interrupted for up to a
 maximum of 14 days until the toxicities dropped to grade 1 or less. Adherence to therapy was
 monitored using drug diaries that were collected at each physician visit and assessed against
 pill counts.
Inclusion Criteria:

 -  squamous cell carcinoma of the head and neck

 -  Tumour site that is amenable to biopsy. Patients can refuse biopsy and still
 participate in the study but all patients must have disease that can be biopsied

 -  Aged 18 years or older

 -  Prior epidermal growth factor receptor (EGFR) based therapy is allowed if greater than
 4 months have elapsed since last dose of that agent and study entry

 -  No chemotherapy or irradiation within the 28-day period preceding entry to the study.

 -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

 -  Ability to understand and the willingness to sign a written informed consent document.

 -  Normal organ and marrow function

 Exclusion Criteria:

 -  Known severe hypersensitivity to Iressa or any of the excipients of this product

 -  Other co-existing malignancies or malignancies diagnosed within the last 3 years with
 the exception of basal cell carcinoma or cervical cancer in situ

 -  Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer
 therapy (except alopecia).

 -  Evidence of any other significant clinical disorder or laboratory finding that makes
 it undesirable for the subject to participate in the trial

 -  Pregnancy or breast feeding women

 -  Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's
 Wort

 -  Treatment with a non-approved or investigational drug within 30 days before Day 1 of
 study treatment

 -  Any evidence of clinically active interstitial lung disease