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Int Poster J Dent Oral Med 3 (2001), No. 4     15. Dec. 2001

Int Poster J Dent Oral Med 2001, Vol 3 No 4, Poster 93

Paclitaxel administration along with antiangiogenic therapy in hnscc xenograft model

Language: English

Author(s):  Christian Küttner MD DDS1, Wolf-D. Beecken MD2, A. Berens MD DDS1, Andreas Eckardt MD DDS PhD1
1Department of Maxillofacial Surgery (Prof. Dr. Dr. J.-E. Hausamen)
Hannover Medical University, 30625 Hannover, Germany
2Clinic of Urology (Prof. Dr. D. Jonas)
Goethe University Hospital, 60590 Frankfurt, Germany

Date/Event/Venue: 
07.29-08.02.2000
5th International Conference on Head and Neck Cancer
San Francisco/USA

Introduction

Angiogenesis is essential for tumor growth and progression [2,6,7]. In head and neck cancer a tight correlation for angiogenesis and tumor progression has been demonstrated. This study was conducted to evaluate if there are additive therapeutic effects combining Paclitaxel with the angiogenesis inhibitor TNP-470 in a mouse model for head and neck cancer.

Material and Methods

NMRI nude mice were inoculated with HNSCC-001 cell line [4]. After 4 weeks of tumor establishment 4 mice were injected with TNP-470 s.c. (30 mg/kg) and Paclitaxel i.p (25 mg/kg) every other day for 12 days while 4 control mice received vehicle injections only. The tumor volume and body weight was measured every other day up to day 15, when all mice were sacrificed. Tumor volume was calculated by using the standard formula: a x b2 x 0,52 where a is the longest diameter and b is the shortest diameter. Tumor volume is also expressed by the ratio of mean tumor volume in treated animals to mean tumor volume in the control animals (T:C ratio). The T:C ratio before treatment was 1,2.

 
Table 1: Tumor volume by formula V=a x b2 x 0,52 [cm3].
  day 0 day 4 day 6 day 8 day 10 day 12 day 15
Taxol/TNP 470 186 207 165 151 145 107 134
Control 160 210 236 344 421 571 739
SF Taxol/TNP 470 42 92 83 74 75 52 55
SF Control 25 13 13 36 34 76 60
t-Test 0,33955 0,94723 0,14241 0,00320 0,00054 0,00006 0,00001
 
Table 2: Body weight [g].
  day 0 day 4 day 6 day 8 day 10 day 12 day 15
Taxol/TNP 470 29,00 31,00 31,00 31,25 31,25 30,75 30,75
Control 28,50 30,00 28,75 25,75 24,75 23,00 22,25
SF Taxol/TNP 470 2,94 2,58 3,92 2,99 3,59 3,50 3,50
SF Control 1,29 2,31 2,36 2,22 3,30 2,83 2,50
t-Test 0,76626 0,58470 0,36315 0,02536 0,03738 0,01373 0,00752
 
Table 3: Ratio of Tumor-Volume T/C.
  day 0 day 4 day 6 day 8 day 10 day 12 day 15
Tumor Volume T/C 1,16 1,06 0,83 0,63 0,56 0,44 0,44
SF 0,26 0,46 0,46 0,48 0,51 0,56 0,56

Results

Significant differences in tumor volume could be observed from day 8 of treatment. On day 15 the tumor volume (Table 1) was 739 ± 60 mm3 in the vehicle-treated group and 136 ± 55 mm3 in the TNP-470/Paclitaxel treated group (p=0,00001). On day 15 the body weight (Table 2) in the control group was 22,3 ± 2,5 g and 30,8 ± 3,5 g in the TNP-470/Paclitaxel group (p=0,008). The T:C ratio decreased gradually during the experiment, from 1,2 before treatment to 0,4 on day 15 when the animals were sacrificed (Table 3). Neither in treatment nor in control group metastasis could be detected macroscopically and in histological examination.

Figure 1:

Figure 2:

Figure 3:

Conclusion

Previous studies have demonstrated that taxanes as well as TNP-470 can decrease tumor progression in xenograft models [1,3,5,8]. The tumor volume was repressed in nude mice bearing human head and neck cancer by the combination of TNP-470 and Paclitaxel.
Further investigation of this combination is warranted.

References

  1. Eckardt A, Kuettner C, Hüttmann C, Berens A: Efficacy of the angiogenesis inhibitor TNP-470 in nude mice bearing squamous cell-carcinoma-xenografts. J Canc Res Clin Oncol Sup, 2000, Vol 126, S.73
  2. Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285, S.1182-6
  3. Hüttmann C, Eckardt A, Fokas K, Haindl J: Experimental chemotherapy of xentransplanted oral squamous cell carcinom: efficiancy of docetaxel (Tacotere) in a nude mouse model. Mund Kiefer Gesichtschir 1999, 3, S.257-262
  4. Knebel J, Eckardt A, Fokas K, Aufderheide M, Nolte N: Continuous cell lines derived from head and neck tumors for mechanistic studies in vitro and in a nude mouse animal model. edited by Werner J, Lippert B, Rudert H. Amsterdamm - Lausanne - New-York - Shanghai, Elsevier, 1996
  5. Ingber D, Fujita T, Kishimoto S, Sudo K, Kanamaru T, Brem H, Folkman J: Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature 1990, 348, S.555-7
  6. O'Reilly MS: The preclinical evaluation of angiogenesis inhibitors. Invest New Drugs 1997, 15, S.5-13
  7. Petruzzelli G: Tumor angiogenesis. Head Neck 1996, 18, S.283-91
  8. Teicher BA, Holden SA, Ara G, Sotomayor EA, Huang ZD, Chen YN, Brem H: Potentiation of cytotoxic cancer therapies by TNP-470 alone and with other anti-angiogenic agents. Int J Cancer 1994, 57, S.920-5

 

This Poster was submitted by Dr. Christian Küttner.

Correspondence address:
Dr. Christian Küttner
Medizinische Hochschule Hannover
Mund-Kiefer-Gesichtschirurgie
Carl-Neuberg-Str. 1
30625 Hannover