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  • Title: Interstitial wires releasing diffusing alpha emitters combined with chemotherapy improved local tumor control and survival in squamous cell carcinoma-bearing mice.
    Author: Cooks T, Arazi L, Efrati M, Schmidt M, Marshak G, Kelson I, Keisari Y.
    Journal: Cancer; 2009 Apr 15; 115(8):1791-801. PubMed ID: 19197995.
    Abstract:
    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 ((224)Ra-)-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 SQ2 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 (224)Ra-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.
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