Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of Vascular Endothelial Growth Factor (VEGF) and Thrombospondin-1 as Biomarkers of Metronomic Chemotherapy in Progressive Pediatric Solid Malignancies

  • Research Paper
  • Published:
Indian Pediatrics Aims and scope Submit manuscript

Abstract

Objectives

We compared Vascular Endothelial Growth factor (VEGF) and Thrombospondin-1 between patients with progressive paediatric malignancies randomized to metronomic chemotherapy versus placebo to determine their role as biomarker.

Methods

In this double-blinded, placebo-controlled randomized study of 108 progressive pediatric malignancies, serum VEGF and thrombospondin-1 levels were evaluated using ELISA at baseline, A2 (week-9 or earlier if progressed) and A3 (week-18 or earlier if progressed).

Results

Mean VEGF and thrombospondin-1 at baseline, A2 and A3 and the change from baseline to A2 were not different between two groups. In metronomic arm, responders (those completing 3 cycles) had significantly lower mean (SD) baseline VEGF levels [659.7(362.1) vs 1143.9 (622.0) µg/mL] (P=0.002) and significant decrease in thrombospondin-1 from baseline to A2 [−4.43(8.0) µg/mL vs 1.7(11.3) µg/mL] (P=0.04), as compared to non-responders. Similar changes were not observed in responders on placebo arm. No consistent trend of these biomarkers was observed.

Conclusions

VEGF and thrombospondin-1 are not reliable biomarkers for response to metronomic chemotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pramanik R, Bakhshi S. Metronomic therapy in pediatric oncology: A snapshot. Pediatr Blood Cancer. 2019;66: e27811.

    Article  Google Scholar 

  2. Bahl A, Bakhshi S. Metronomic chemotherapy in progressive pediatric malignancies: Old drugs in new package. Indian J Pediatr. 2012;79: 1617–22.

    Article  Google Scholar 

  3. Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24: 16–24.

    Article  CAS  Google Scholar 

  4. Rini BI, Michaelson MD, Rosenberg JE, Bukowski RM, Sosman JA, Stadler WM, et al. Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. J Clin Oncol. 2008;26:3743–8.

    Article  CAS  Google Scholar 

  5. Stempak D, Gammon J, Halton J, Moghrabi A, Koren G, Baruchel S. A pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors. J Pediatr Hematol Oncol. 2006;28: 720–8.

    Article  CAS  Google Scholar 

  6. Kieran MW, Turner CD, Rubin JB, Chi SN, Zimmerman MA, Chordas C, et al. A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer. J Pediatr Hematol Oncol. 2005;27: 573–81.

    Article  Google Scholar 

  7. Robison NJ, Campigotto F, Chi SN, Manley PE, Turner CD, Zimmerman MA, et al. A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer. Pediatr Blood Cancer. 2014;61: 636–42.

    Article  Google Scholar 

  8. Kesari S, Schiff D, Doherty L, Gigas DC, Batchelor TT, Muzikansky A, et al. Phase II study of metronomic chemotherapy for recurrent malignant gliomas in adults. Neuro-Oncol. 2007;9: 354–63.

    Article  CAS  Google Scholar 

  9. Pramanik R, Agarwala S, Gupta YK, Thulkar S, Vishnubhatla S, Batra A, et al. Metronomic chemotherapy vs best supportive care in progressive pediatric solid malignant tumors: A randomized clinical trial. JAMA Oncol. 2017;3: 1222–7.

    Article  Google Scholar 

  10. Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, Tong RT, et al. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol. 2005; 23:8136–9.

    Article  Google Scholar 

  11. Burstein HJ, Chen Y-H, Parker LM, Savoie J, Younger J, Kuter I, et al. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res 2008;14:7871–7.

    Article  CAS  Google Scholar 

  12. Tuszynski GP, Gasic TB, Rothman VL, Knudsen KA, Gasic GJ. Thrombospondin, a potentiator of tumor cell metastasis. Cancer Res. 1987;47: 4130–3.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

    Raja Pramanik, Anudishi Tyagi, Deepa Dhawan & Sameer Bakhshi

  2. Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India

    Sandeep Agarwala

  3. Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India

    Sreenivas Vishnubhatla

Authors
  1. Raja Pramanik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anudishi Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandeep Agarwala
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sreenivas Vishnubhatla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Deepa Dhawan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sameer Bakhshi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sameer Bakhshi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pramanik, R., Tyagi, A., Agarwala, S. et al. Evaluation of Vascular Endothelial Growth Factor (VEGF) and Thrombospondin-1 as Biomarkers of Metronomic Chemotherapy in Progressive Pediatric Solid Malignancies. Indian Pediatr 57, 508–511 (2020). https://doi.org/10.1007/s13312-020-1845-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13312-020-1845-3

Keywords

Trial registration

Search

Navigation