Ph II Trial of Induction Chemotherapy With Carboplatin and Paclitaxel, Followed by Concurrent Chemotherapy/Radiation Therapy With ZD1839 (IRESSA), 5-FU, Hydroxyurea, and Twice-Daily Radiation, Followed by Adjuvant ZD1839 Monotherapy in Patients With Locally Advanced Head & Neck Cancer
1. Histologically or cytologically confirmed diagnosis of squamous cell or poorly
differentiated carcinomas, or lymphoepithelioma of the nasopharynx.
2. Age 18 years or older.
3. Patients with AJCC (6th edition, 2002) stage III or IV head and neck cancer.
4. Patients with AJCC (6th edition, 2002) stage IV head and neck cancer. presenting with
cervical lymph node metastasis of an unknown primary (i.e., TxN2 or TxN3) are also
5. Prior to entry in the study, the resectability and alternative treatment options for
each patient will be determined by a team composed of a head and neck surgeon, a
radiation oncologist,and a medical oncologist. Stage determination, optimal local
treatment, and its timing according to this protocol will be determined at this
evaluation. Each patient will be classified as having resectable or unresectable
disease. The unequivocal demonstration of distant metastasis (M1) confers
6. Unidimensionally measurable disease (based on RECIST) is desirable but not strictly
required. Individuals who are disease free at baseline after excisional biopsy or
node dissection will be considered not evaluable for response assessment but are
7. No prior or radiotherapy.
8. Prior surgical therapy will consist only of incisional or excisional biopsy and
organ-sparing procedures such as debulking of airway-compromising tumors or neck
dissection in a patient with an unknown primary tumor.
9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%.
10. Patients must have normal organ and marrow function as defined below absolute
neutrophil count (ANC) ≥ 1,500/μl platelets
≥ 100,000/μl total bilirubin within normal institutional
limits aspartate aminotransferase (AST, SGOT)/ alanine aminotransferase (ALT, SGPT)
≤ 2.5 × institutional upper limit of normal alkaline phosphatase
≤ 2 × upper limit of normal creatinine within
normal institutional limits
1. Unequivocal demonstration of metastatic disease (i.e. M1 disease).
2. Known severe hypersensitivity to ZD1839 or any of the excipients of this product.
3. Any coexisting malignancy that would increase risk of toxicity, interfere with
interpretation of toxicity, or is associated with a median survival of less than 24
4. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital,
or St.John's Wort.
5. Treatment with an investigational drug within 30 days before Day 1 of trial
6. Incomplete healing from previous surgery.
7. Pregnancy or breast feeding (women of child-bearing potential). Patients should be
advised to use effective contraception as appropriate.
8. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to paclitaxel, Cremaphor EL, carboplatin, 5 FU, or hydroxyurea.
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection,symptomatic congestive heart failure (CHF), unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.
10. Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any
history of clinically significant CHF are excluded. The exclusion of patients with
active coronary artery disease will be at the discretion of the attending physician.
11. Patients must have no uncontrolled active infection other than that not curable
without treatment of their cancer.
12. No patients with severe baseline neurologic deficits (> grade II neuropathy) will be
treated with induction chemotherapy.
13. Any evidence of clinically active interstitial lung disease (patients with chronic
stable radiographic changes who are asymptomatic need not be excluded.