Efficacy and Safety Study of Leukocyte Interleukin,Injection (LI) to Treat Cancer of the Oral Cavity

Head and neck carcinomas constitute about 5% of all cancers annually worldwide. In the US
there are about 37,000 new cases annually. Ninety percent are advanced primary squamous cell
carcinoma (SCCHN). Approximately 2/3 of SCCHN patients present on their first visit with
locally advanced disease. The median 3 year overall survival(OS) for these patients with
existing standard of care (SOC) therapies - surgery followed by radiotherapy or combined
radiochemotherapy - is between 52 and 55%; the 5 year OS is 43%. There are clearly a large
number of SCCHN patients not well served by available modalities.

Regional intra or perilymphatic and/or intratumoral or peritumoral low dose cytokine therapy
may have important therapeutic effects in SCCHN patients and constitute an additional
anti-tumor mechanism of action different and distinct from current SOC. Leukocyte Interleukin
Injection (LI) [Multikine]contains a defined mixture of naturally derived cytokines and
chemokines with demonstrated safety and immunomodulatory activity in animals and in man in
Phase 1 and 2 clinical trials. LI was administered prior to SOC and in combination with low
non-chemotherapeutic doses of cyclophosphamide, indomethacin, and zinc (CIZ) in studies with
LI. The results of these studies indicate that the local/regional injection of mixed
interleukins (LI) with CIZ prior to SOC can overcome local immunosuppression, break tumor
tolerance to tumor antigens and allow for a sustainable and effective anti-tumor immune
response.

LI is being tested in this large, global, multinational Phase III clinical trial to develop
definitive proof of its efficacy and safety in treating SCCHN. The trial is an open-label
randomized multi-center controlled study of LI + CIZ + SOC in subjects with advanced primary
SCCHN of the oral cavity/soft palate vs. SOC [The Comparator Arms for, Overall Survival, the
Primary End Point of this Study].

Inclusion Criteria:

- Untreated SCCHN of oral cavity/soft palate, categories
T1N1-2M0,T2N1-2M0,T3N0-2M0,T4N0-2M0 (T4 allowed only if invasion of mandible is
negligible) scheduled for SOC

- Primary tumor and any positive node(s)measurable in 2 dimensions

- normal immune function

- no immunosuppressives with 1 year

- KPS>70

- Age>18

- Male or Female (non-pregnant)

- Life expectancy >6mo.

- Able to take oral medication

- Able to provide informed consent

Exclusion Criteria:

- Subjects to be treated with other than SOC

- Tumor invasion of bone (also see inclusion criteria)

- Tumor classifications T1N0, T2N0, T4N3, any TN classification with M1

- Tumors in locations other than those specified in inclusion criteria

- Active peptic ulcer

- Prior resection of jugular nodes ipsilateral to tumor

- Acute or chronic viral, bacterial immune or other disease associated with abnormal
immune function

- Subjects on hemodialysis or peritoneal dialysis

- History of asthma

- Any condition that in the opinion of the investigator would cause the subject to be
unable to participate or tolerate the protocol regimen