Phase II Study of Skin Toxicity Dosing of IRESSA (Gefitinib) in Squamous Cell Carcinoma of the Head and Neck

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