Abstract
Background Razoxane and vindesine were shown to suppress distant metastasis in animal systems. Both drugs affect main steps of the metastatic cascade. Therefore, a pilot study was performed to study the influence of these drugs on the dynamics of metastasis in advanced soft tissue sarcomas (STS). This study was now updated. Methods Twenty-three patients with unresectable (n = 7) and oligometastatic STS (n = 16) received a basic treatment with razoxane and vindesine supported by radiotherapy and occasionally by surgery. Long-term treatment was intended in patients with metastatic disease. The cumulative number of new metastases after 6 and 9 months were determined. Thirty-six patients with comparable stages of STS treated with contemporary chemotherapy served as non-randomized, retrospective controls. The prognostic parameters of the groups were comparable. Results In patients receiving razoxane and vindesine, the median number of new metastases after 6 months was 0 (range, 0–40) and after 9 months likewise 0 (0–70). The corresponding numbers in the control group were 4.5 (range, 0–40) and 9 (0–>100) (P < 0.001). The progression-free survival at 6 months was 74% in the study group and 23% in the controls. The median survival time from the occurrence of the first metastasis or the time of unresectability was 20+ months (range, 8–120+) versus 9 months (range, 2–252) (P < 0.001). The combined treatment was associated with a low to moderate toxicity. Conclusions Trimodal treatment with razoxane, vindesine, and radiotherapy is feasible in patients with unresectable primaries and early metastatic STS. The combination inhibits the development of remote metastases in a majority of the patients and prolongs survival.
Similar content being viewed by others
References
Rhomberg W, Hassenstein EOM, Gefeller D (1996) Radiotherapy vs. radiotherapy and razoxane in the treatment of soft tissue sarcomas: final results of a randomized study. Int J Radiat Oncol Biol Phys 36:1077–1084
Rhomberg W, Eiter H, Schmid F, Saely CH (2007) Razoxane and vindesine in advanced soft tissue sarcomas: impact on metastasis, survival and radiation response. Anticancer Res 27(5)
De Vita VT Jr, Hellman S, Rosenberg SA (eds) (2001) Cancer principles & practice of oncology. JB Lippincott Comp, Philadelphia, pp 1879–1883
Storme GA, Schallier DC, De Neve WJ et al (1988) Vinblastine has radiosensitizing activity in limited squamous cell lung cancer. Int J Radiat Oncol Biol Phys 15(Suppl 1):222
Rhomberg W, Eiter H, Soltesz E et al (1990) Long term application of vindesine: toxicity and tolerance. J Cancer Res Clin Oncol 116:651–653
Atassi G, Dumont P, Vandendris M (1982) Investigation of the in vivo anti-invasive and anti-metastatic effect of desacetyl vinblastine amide sulphate or vindesine. Invasion Metastasis 2:217–231
Mareel MM, Bracke ME, Boghaert ER (1986) Tumor invasion and metastasis: therapeutic implications? Radiother Oncol 6:135–142
Haug IJ, Siebke EM, Grimstad IA et al (1993) Simultaneous assessment of migration and proliferation of murine fibrosarcoma cells, as affected by hydroxyurea, vinblastine, cytochalasin B, razoxane and interferon. Cell Prolif 26:251–261
Mareel MM, Storme GA, De Bruyne GK et al (1982) Vinblastin, vincristine and vindesine: antiinvasive effect on MO4 mouse fibrosarcoma cells in vitro. Eur J Cancer Clin Oncol 18:199–210
Hellmann K, Murkin GE (1974) Synergism of ICRF 159 and radiotherapy in the treatment of experimental tumors. Cancer 34:1033–1039
Tanabe K, Ikegami Y, Ishida R, Andoh T (1991) Inhibition of topoisomerase II by antitumor agents bis(2,6-dioxopiperazine) derivatives. Cancer Res 51:4903–4908
Karakiulakis G, Missirlis E, Maragoudakis ME (1989) Mode of action of razoxane: inhibition of basement membrane collagen-degradation by a malignant tumor enzyme. Methods Find Exp Clin Pharmacol 11:255–261
Hellmann K, Burrage K (1969) Control of malignant metastases by ICRF 159. Nature 224:273–275
Le Serve AW, Hellmann K (1972) Metastases and the normalization of tumor blood vessels by ICRF-159: a new type of drug action. Br Med J 1:597–601
Hellmann K (2003) Dynamics of tumour angiogenesis: effect of razoxane-induced growth rate slowdown. Clin Exp Metastasis 20:95–102
Salsbury AJ, Burrage K, Hellmann K (1974) Histological analysis of the antimetastatic effect of 1,2-Bis (3,5-dioxo-piperazin-1-yl)-propane. Cancer Res 34:843–849
Baker D, Constable W, Elkon D, Rinehart L (1981) The influence of ICRF 159 and levamisole on the incidence of metastases following local irradiation of a solid tumor. Cancer 48:2179–2183
Peters LJ (1975) A study of the influence of various diagnostic and therapeutic procedures applied to a murine squamous carcinoma on its metastatic behaviour. Br J Cancer 32(3):355–365
Antman K, Crowley J, Balcerzak SP et al (1993) An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol 11:1276–1285
Edmonson JH, Ryan LM, Blum RH et al (1993) Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 11:1269–1275
Santoro A, Tursz T, Mouridsen H et al (1995) Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first line treatment of advanced soft tissue sarcomas: a randomized study of the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 13:1537–1545
Rööser B, Attewell R, Berg NO, Rydholm A (1988) Prognostication in soft tissue sarcoma. A model with four risk factors. Cancer 61:817–823
Zagars GK, Ballo MT, Pisters PWT et al (2003) Prognostic factors for disease-specific survival after first relapse of soft-tissue sarcoma: analysis of 402 patients with disease relapse after initial conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys 57:739–747
Komdeur R, Hoekstra HJ, van den Berg E et al (2002) Metastasis in soft tissue sarcomas: prognostic criteria and treatment perspectives. Cancer Metastasis Rev 21:167–183
Kerbel RS (2001) Clinical trials of antiangiogenic drugs: opportunities, problems, and assessment of initial results. J Clin Oncol 19(Suppl):45s–51s
Klement G, Baruchel S, Rak J et al (2000) Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 105:R15–R24
Hofland KF, Thougaard AV, Dejligbjerg M et al (2005) Combining etoposide and dexrazoxane synergizes with radiotherapy and improves survival in mice with central nervous system tumors. Clin Cancer Res 11:6722–6729
D’Adamo DR, Anderson SE, Albritton K et al (2005) Phase II study of doxorubicin and bevacizumab for patients with metastatic soft-tissue sarcomas. J Clin Oncol 23:7135–7142
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rhomberg, W., Eiter, H., Schmid, F. et al. Combined vindesine and razoxane shows antimetastatic activity in advanced soft tissue sarcomas. Clin Exp Metastasis 25, 75–80 (2008). https://doi.org/10.1007/s10585-007-9103-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10585-007-9103-9