Polymer chemotherapy for head and neck cancer

Objectives: To study a new method of delivery of chemotherapy for the treat ment of squamous cell carcinomas (SCCs) of the head and neck, to evaluate t he pharmacokinetics of four anticancer agents (cisplatin, fluorouracil [5-F U], methotrexate [MTX], and paclitaxel) loaded into the biodegradable polym er, polyanhydride polymer poly(FAD:SA), and to evaluate the effectiveness a nd toxicity of the drug-polymer combination against human SCCs, both in vit ro and in vivo. Study Design: Poly(FAD:SA) was loaded with different chemot herapeutic drugs and its in vitro and in vivo drug release and tissue penet ration characteristics were studied. The biocompatibility and toxicity of t he polymer-drug combination were determined. The effectiveness of the drug polymer was evaluated against three different human SCCs (larynx O11, phary nx FADU, and floor of mouth UM-SCC1) cultured in vitro and in nude mice car rying human SCC xenografts. Methods: The in vitro drug release pharmacokine tics of the drugs were performed using atomic absorption spectrometry for c isplatin and high-pressure liquid chromatography for the 5-FU, MTX, and pac litaxel studies. In vitro tumor cytotoxicity was assessed by growth assay. In vivo cytotoxicity was assessed by growth rate inhibition in a nude mouse model. Results: All four chemotherapy drugs demonstrated a continuous rele ase that followed first-order kinetics from the polymer. More than 95% of t he MTX and 5-FU, 70% of the cisplatin, and 20% of the paclitaxel was releas ed within the 10 days of the assay. Tumor cytotoxicity revealed that the po lymer was very effective against the human SCCs Oil, FADU, and UM-SCC1 in v itro. When a small amount of polymer (1-2 g) was added to the cell culture and left for 7 days, 96.6% of the UM-SCC1 cells, 86.9% of the FADU cells, a nd 94.6% of the O11 cells were killed. When the culture medium was then cha nged every 2 days to remove the effect of nutrient depletion or chemicals r eleased by the degrading polymer, 74% of the UM-SCC1 cells, 94.5% of the FA DU cells, and 66.1% of the O11 cells were killed at 7 days. The tumor anima l model was the nude mouse carrying human floor of mouth SCC xenografts. Di fferent amounts of cisplatin were incorporated into the polymers (5% and 7% drug/polymer at a weight/weight [wt/wt] load). Thirty-five days after impl antation of the polymer in nude mice, the mean treated tumor size was 65.5% of controls in the 5% group and 31.8% in the 7% group. Seventy days after implantation the mean treated tumor size was 41.4% of controls in the 5% gr oup and 38.1% in the 7% group, indicating a statistically significant delay of tumor growth compared with controls or with intraperitoneally injected cisplatin. The blank polymer was well tolerated by the mouse and had no eff ect on tumor growth. Conclusions: The study results indicate that polymer c hemotherapy is effective against a variety of SCCs of the head and neck, bo th in vitro and in vivo, and may become a useful therapeutic option for hea d and neck cancer.