Cisplatin is a highly active drug against squamous cell cancer as measured by response rate. Clinical trials have shown no clear survival benefit to patients with head and neck squamous cell cancer treated with cisplatin either as a single agent, combined with other antineoplastic drugs or with concurrent radiation therapy. Preliminary data suggest that retinoic acid and cisplatin are synergistic in cell culture.
The specific aim of this proposal is to conduct a Phase I clinical trial of 13-cis retinoic acid (13-CRA) administered concurrently with a regimen of cisplatin based chemoradiation for advanced head and neck squamous cell cancer. The goal of the protocol is to define the maximum tolerated dose of 13-CRA in combination with high dose cisplatin and radiation. Tumor samples will be collected prior to and 24 hours after initiating treatment. These samples will be analyzed for tumor platinum levels and induction of genes thought to be markers of early tumor response and platinum resistance. If patients are able to tolerate the addition of CRA to this cisplatin based regimen, a Phase II trial will follow to test therapeutic efficacy.
| Weisman, R A; Christen, R; Los, G et al. (1998) Phase I trial of retinoic acid and cis-platinum for advanced squamous cell cancer of the head and neck based on experimental evidence of drug synergism. Otolaryngol Head Neck Surg 118:597-602 |
| Weisman, R A; Christen, R D; Jones, V E et al. (1998) Observations on control of N2 and N3 neck disease in squamous cell carcinoma of the head and neck by intra-arterial chemoradiation. Laryngoscope 108:800-5 |
