Interstitial Wires Releasing Diffusing Alpha Emitters Combined With Chemotherapy Improved Local Tumor Control and Survival in Squamous Cell Carcinoma-bearing Mice

BACKGROUND: The objective of this study was to examine the combined effect of diffusing alpha-emitter radiation therapy (DART) together with the chemotherapeutic agent cisplatin on tumor development. METHODS: BALB/c mice bearing squamous cell carcinoma tumors were treated with radium 224 (Ra-224-)-loaded stainless steel wires, releasing short-lived, alpha-emitting atoms from their surface. A concomitant regimen of cisplatin doses (5 mg/kg per dose) was given intravenously for the evaluation of the combined effect. Animals were monitored for tumor growth and survival. RESULTS: First, the authors observed that alpha particles and cisplatin inhibited SQ(2) cell proliferation in vitro and promoted apoptosis. Treatment of tumor-bearing mice indicated that, when a regimen of 2 separate doses of cisplatin was given concomitantly with a single intratumoral Ra-224-loaded wire, there was moderate tumor growth inhibition relative to what was observed from each treatment alone. When tumors were treated with 2 radioactive wires positioned near the tumor base and a similar drug administration, the growth arrest effect intensified, and there also was a significant increase in survival rates. The combined treatment reduced both local tumor growth and metastatic spread to the lungs. CONCLUSIONS: Antitumor activity and overall survival of metastatic tumor-bearing mice were improved significantly by the combined treatment. These results highlight the potential benefit of alpha radiation-based radiotherapy in combination with chemotherapeutic drugs for anticancer treatment. Cancer 2009;115:1791-801. (C) 2009 American Cancer Society.