Trial Information

Erlotinib (Tarceva) Given Intermittently During First Line Standard Platinum Containing Chemotherapy for Advanced Squamous Cell Carcinoma of the Head and Neck

We hypothesize that Erlotinib fails to enhance the effects of chemotherapy on response and
survival because of Erlotinib's cytostatic effect, this results in a slowing down of the
cell cycle, this in turn results in a hampering of the cytotoxic effect of chemotherapy
leading to a lack of synergism with the combination. We propose that a sequential approach
to the combination allows each drug to be used in its optimum time, by sequencing the
Erlotinib, giving it 24 hours after chemotherapy we allow the chemotherapy to exert its
effect with cells actively in cell cycle, but delivering the Erlotinib at a time when cells
are trying to return to cell cycle hence slowing the growth rate of the tumor cell
population. By withdrawing the Erlotinib about 4 days prior to the next chemotherapy cycle,
we allow the cells to go back into cell cycle and therefore become susceptible to
chemotherapy again.

Patients will be treated with intravenous paclitaxel over 3 hours followed by intravenous
cisplatin/carboplatin on Day 1 of each 21 day cycle. Patients will be treated with Erlotinib
at a loading dose of 300mg on Day 2 followed by 150 mg orally daily from Days 3-17 of each
cycle of paclitaxel and cisplatin/carboplatin.

The primary objectives of this study are to assess the response rate of combination of
erlotinib, cisplatin/carboplatin and paclitaxel in the first line treatment setting of
metastatic, recurrent and persistent squamous cell carcinoma of the head and neck.
Secondary objectives are to assess toxicity, median survival, and progression free survival.