Retention of intratumor injections of cisplatinum in murine tumors and the impact on laser thermal therapy for cancer treatment

TOX-PK Consultancy, San Diego, CA, USA.
Archives of Oto-Rhino-Laryngology (Impact Factor: 1.55). 08/2008; 266(2):279-84. DOI: 10.1007/s00405-008-0736-3
Source: PubMed


Recent studies using murine models of human squamous cell carcinoma (SCCA) have revealed a significant improvement in survival and cure rate of animals transplanted with human SCCA when treated with a combination 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 different 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 significantly 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 effective treatment for head and neck SCCA.

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    • "The vascular collapse will avoid systemic diffusion of cisplatin and allow us to attain a very high concentration of CPPD in the tumor margins as first suggested by Sakurai et al., in 1996. High doses of CDDP/sol will significantly improve the combined treatment proposed (Kanekal et al., 2009). Further progress in laser chemotherapy may be an outgrowth of the current excitement surrounding nanoscience and the promise of new nanoscale applications in cancer diagnostics and therapy. "
    Current Cancer Treatment - Novel Beyond Conventional Approaches, 12/2011; , ISBN: 978-953-307-397-2
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    ABSTRACT: To review the outcomes of a phase II study using laser-induced thermal therapy (LITT) as a palliative treatment for 106 patients with recurrent head and neck tumors. Retrospective study. Tertiary hospital in the United States. The primary endpoints were tumor response and survival. Prognostic values were assessed by the Kaplan-Meier method. The best results were seen in oral cavity tumors, in which mean survival was 29.1 months, as compared to neck tumors (mean 14.4 +/- 6.9 months; range 7.5-20.7 months; with a 95% confidence interval). Further analysis showed that clinical factors such as gender, smoking, and alcohol use were not indicators of poor prognosis, whereas neck disease and tumor stage at first treatment were relevant factors. In this study, 40 out of 106 patients treated by LITT remained alive at the end of our follow-up, and a complete response was seen in 24 (22.6%) patients. The highest response rate was seen in oral cavity tumors, which suggests that tumor location at this site may be a predictor of favorable outcome with LITT.
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    ABSTRACT: To evaluate the therapeutic efficacy of a novel modular polymer platform in the treatment of head and neck squamous cell carcinoma (HNSCC). In vivo study. Academic research laboratory. Subjects and C3H/HeJ mice and SCID/beige mice were randomized to receive implantation of no polymer, plain polymer, plain polymer with local cisplatin injection, or cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive 4 Gy of external beam radiation for 4 days or no radiation. Tumor size was measured until the mice were humanely killed. At necropsy, the tumors were excised and weighed. There was a significant reduction in tumor growth using this novel polymer platform. The cisplatin-secreting polymer effectively reduced human head and neck tumor growth in SCID mice by 17-fold and SCC VII/SF tumors in C3H/HeJ mice by more than 16-fold compared with the control, plain polymer, and plain polymer + intratumoral cisplatin injection groups (P = .01 for both). We also observed a statistically significant lower tumor weight in mice treated with cisplatin polymer and concomitant radiation compared with the radiation alone and control groups. We demonstrate the efficacy of a novel polymer platform in delivering cisplatin to a partially resected SCC in a murine model. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan for validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC.
    Archives of otolaryngology--head & neck surgery 04/2012; 138(4):412-7. DOI:10.1001/archoto.2012.20 · 2.33 Impact Factor
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