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
Head and Neck

Abstract

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.

Keywords

Cisplatin Biodistribution Intratumor-injections Squamous cell carcinoma Laser-induced thermal therapy 

Notes

Acknowledgments

This study was supported by the Division of Head and Neck Surgery, the Jonsson Comprehensive Cancer, UCLA School of Medicine, and NIH Grant # CA 88921-01.

References

  1. 1.
    Forastiere AA, Trotti A, Pfister DG et al (2006) Head and neck cancer: recent advances and new standards of care. J Clin Oncol 24:2603–2605PubMedCrossRefGoogle Scholar
  2. 2.
    Paiva MB, Blackwell KE, Saxton RE et al (1998) Palliative laser therapy for recurrent head and neck cancer: a Phase II clinical study. Laryngoscope 108:1277–1283PubMedCrossRefGoogle Scholar
  3. 3.
    Bublik M, Sercarz JA, Lufkin RB et al (2006) Ultrasound-guided laser-induced thermal therapy of malignant cervical adenopathy. Laryngoscope 116:1507–1511PubMedCrossRefGoogle Scholar
  4. 4.
    Joffee S, Tajiri H, Oguro Y et al (1989) Laserthermia: a new method of interstitial local hyperthermia using the contact Nd:Yag laser. Radiol Clin North AM 27:611–620Google Scholar
  5. 5.
    Paiva MB, Saxton RE, Letts GA et al (1995) Interstitial laser photochemotherapy with new anthrapyrazole drugs for the treatment of xenograft tumors. J Clin Laser Med Surg 13:307–313PubMedGoogle Scholar
  6. 6.
    Graeber IP, Paiva MB, Eshraghi AA et al (1998) Anthrapyrazoles and interstitial laser phototherapy for experimental treatment of squamous cell carcinoma. Laryngoscope 108:351–357PubMedCrossRefGoogle Scholar
  7. 7.
    Paiva MB, Bublik M, Castro DJ et al (2005) Intratumor injections of cisplatin and laser thermal therapy for palliative treatment of recurrent cancer. Photomed Laser Surg 23:531–535PubMedCrossRefGoogle Scholar
  8. 8.
    Bernier J, Cooper JS, Pajak TF et al (2005) Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27:843–850PubMedCrossRefGoogle Scholar
  9. 9.
    Paiva MB, Saxton RE, Letts G et al (1996) Laser photochemotherapy with anthracyclines on cultured human squamous carcinoma cells. Laryngoscope 106:257–262PubMedCrossRefGoogle Scholar
  10. 10.
    Paiva M, Saxton R, Blackwell K et al (2000) Combined cisplatinum and laser thermal therapy for palliation of recurrent head and neck tumors. Diagn Ther Endosc 6:133–140PubMedCrossRefGoogle Scholar
  11. 11.
    Clayman GL, Dreiling LK (1999) Injectable modalities as local and regional strategies for head and neck cancer. Hematol Oncol Clin North Am 13:787–810 viiiPubMedCrossRefGoogle Scholar
  12. 12.
    Kanekal S, Sahai A, Jones R et al (1995) Enhanced retention of 195 m pt-cisplatinum in murine tumors with a novel injectable sustained-release drug delivery system. 86th Annual Meeting of the American Association for Cancer Research, Toronto, Ontario, Canada.Google Scholar
  13. 13.
    Marchesini R, Andreola S, Emanuelli H et al (1985) Temperature rise in biological tissue during Nd:YAG laser irradiation. Lasers Surg Med 5:75–82PubMedCrossRefGoogle Scholar
  14. 14.
    Firusian N (1988) Chemo- and laser therapy of advanced tumors of the upper gastrointestinal tract. Onkologie 11:23–33PubMedCrossRefGoogle Scholar
  15. 15.
    Ohno S, Siddik ZH, Kido Y et al (1994) Thermal enhancement of drug uptake and DNA adducts as a possible mechanism for the effect of sequencing hyperthermia on cisplatin-induced cytotoxicity in L1210 cells. Cancer Chemother Pharmacol 34:302–306PubMedCrossRefGoogle Scholar
  16. 16.
    Engin K (1996) Clinical experience with hyperthermia. Control Clin Trials 17:316–342PubMedCrossRefGoogle Scholar
  17. 17.
    Beketic-Oreskovic L, Jaksic M, Oreskovic S et al (1997) Hyperthermic modulation of resistance to cis-diamminedichloroplatinum (II) in human larynx carcinoma cells. Int J Hyperthermia 13:205–214PubMedCrossRefGoogle Scholar
  18. 18.
    Arancia G, Crateri Trovalusci P, Mariutti G et al (1989) Ultrastructural changes induced by hyperthermia in Chinese hamster V79 fibroblasts. Int J Hyperthermia 5:341–350PubMedCrossRefGoogle Scholar
  19. 19.
    Zanke BW, Boudreau K, Rubie E et al (1996) The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat. Curr Biol 6:606–613PubMedCrossRefGoogle Scholar
  20. 20.
    Hettinga JV, Lemstra W, Meijer C et al (1994) Hyperthermic potentiation of cisplatin toxicity in a human small cell lung carcinoma cell line and a cisplatin resistant subline. Int J Hyperthermia 10:795–805PubMedCrossRefGoogle Scholar
  21. 21.
    Kitamura K, Kuwano H, Matsuda H et al (1992) Synergistic effects of intratumor administration of cis-diamminedichloroplatinum(II) combined with local hyperthermia in melanoma bearing mice. J Surg Oncol 51:188–194PubMedCrossRefGoogle Scholar
  22. 22.
    Burris HA 3rd, Vogel CL, Castro D et al (1998) Intratumoral cisplatin/epinephrine-injectable gel as a palliative treatment for accessible solid tumors: a multicenter pilot study. Otolaryngol Head Neck Surg 118:496–503PubMedCrossRefGoogle Scholar
  23. 23.
    Castro DJ, Sridhar KS, Garewal HS et al (2003) Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America. Head Neck 25:717–731PubMedCrossRefGoogle Scholar
  24. 24.
    Ning S, Yu N, Brown DM, Kanekal S et al (1999) Radiosensitization by intratumoral administration of cisplatin in a sustained-release drug delivery system Intratumoral radioimmunotherapy of a human cancer xenograft using a sustained-release gel. Radiother Oncol 50:215–223PubMedCrossRefGoogle Scholar
  25. 25.
    Sakurai K, Yoshiga K, Tsumura M et al (1996) Effects of thermochemotherapy [1-hexylcarbamoyl-5-fluorouracil (HCFU) combined with hyperthermia]: a basic study on the most effective timing and sequence in vivo. Anticancer Res 16:2729–2733PubMedGoogle Scholar
  26. 26.
    Wang Y, Zhou C, Jia J et al (2001) Endoscopic Nd:YAG laser therapy combined with local chemotherapy of superficial carcinomas of the oesophagus and gastric cardia. Lasers Med Sci 16:299–303PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Sarath Kanekal
    • 1
  • Jayne Joo
    • 2
  • Michael Bublik
    • 3
  • Adir Bababeygy
    • 2
  • Christopher Loh
    • 2
  • Dan J. Castro
    • 2
  • Joel A. Sercarz
    • 2
  • Marcos B. Paiva
    • 2
    • 4
  1. 1.TOX-PK ConsultancySan DiegoUSA
  2. 2.UCLA Department of Surgery, Division of Head and Neck SurgeryDavid Geffen School of Medicine at the University of CaliforniaLos AngelesUSA
  3. 3.Department of Head and Neck Surgery-OtolaryngologyMiller School of Medicine at the University of MiamiMiamiUSA
  4. 4.David Geffen School of Medicine at UCLALos AngelesUSA

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