Eur Arch Otorhinolaryngol (2009) 266:279–284 DOI 10.1007/s00405-008-0736-3 123 HEAD AND NECK Retention of intratumor injections of cisplatinum in murine tumors and the impact on laser thermal therapy for cancer treatment Sarath Kanekal · Jayne Joo · Michael Bublik · Adir Bababeygy · Christopher Loh · Dan J. Castro · Joel A. Sercarz · Marcos B. Paiva Received: 15 October 2007 / Accepted: 29 May 2008 / Published online: 8 July 2008 Springer-Verlag 2008 Abstract Recent studies using murine models of human squamous cell carcinoma (SCCA) have revealed a signiW- cant improvement in survival and cure rate of animals transplanted with human SCCA when treated with a combi- nation of intratumor injections of chemotherapy and laser induced thermal therapy (LITT). These preliminary results suggest that this novel combination therapy may lead to improved clinical response compared to either treatment modality alone. Using a murine model of human SCCA we investigated two diVerent modes of intratumor injection of cisplatin: a sustained-release cisplatin gel implant (CDDP/ gel) versus cisplatin in solution (CDDP) at varying doses (range 1–3 mg/ml). In addition, we tested CDDP/gel combined with LITT. Results showed optimal drug concentration (30–300 nM) at tumor margins up to 4 h after injection of CDDP/gel implant compared to 3 nM at 5 min after injection with CDDP solution. Combined CDDP/gel and laser therapy signiWcantly decreased tumor volume (P < 0.05), with recurrence in only 25% of animals tested, compared to 78% tumor regrowth after LITT alone. These results suggest that laser chemotherapy may be an eVective treatment for head and neck SCCA. Keywords Cisplatin · Biodistribution · Intratumor-injections · Squamous cell carcinoma · Laser-induced thermal therapy Introduction Recurrent or advanced head and neck cancer is a common clinical dilemma because of limited treatment options and poor prognosis [1]. At the University of California, Los Angeles (UCLA) we have developed laser induced/intersti- tial thermal therapy (LITT), currently in Phase II trials, as a palliative treatment for patients with advanced and recur- rent head and neck tumors as an alternative to more radical surgery [2, 3]. Although LITT procedures are safe, feasible, and can extend survival, recurrence at tumor margins is seen in many cases, particularly after palliative treatment via endoscopic recanalization of advanced obstructing can- cers of the gastrointestinal and bronchial tracts [3, 4]. Dur- ing LITT high photothermal laser energy levels are delivered to the area of maximum obstruction inducing irre- versible coagulative changes while lower levels are deliv- ered to the tumor margin [4]. Reversible hyperthermic damage at the margins frequently leads to tumor recur- rence, requiring additional application of laser therapy for tumor eradication [5–7]. In general, microscopic disease at Presented at the 2005 Annual Meeting of the Academy of Otolaryngology, Head and Neck Surgery. September 26, 2005, Los Angeles, CA, USA. S. Kanekal TOX-PK Consultancy, San Diego, CA, USA J. Joo · A. Bababeygy · C. Loh · D. J. Castro · J. A. Sercarz · M. B. Paiva (&) UCLA Department of Surgery, Division of Head and Neck Surgery, David GeVen School of Medicine at the University of California, Box 162418, 62-132 CHS, Los Angeles, CA 90095-1624, USA e-mail: mpaiva@ucla.edu M. Bublik Department of Head and Neck Surgery-Otolaryngology, Miller School of Medicine at the University of Miami, Miami, FL, USA M. B. Paiva David GeVen School of Medicine at UCLA, 10833 LeConte Avenue 62-132, Los Angeles, CA 90095-1624, USA