827P - Interim results of a phase II study of sunitinib and low dose metronomic cyclophosphamide in advanced renal cell cancer

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Cytotoxic agents
Renal Cell Cancer
Therapy
Biological therapy
Presenter Muhammad Khattak
Authors M.A. Khattak1, K. Edmonds2, K. Khabra3, A. Sohaib4, K. Pennert3, L. Pickering2, M.E. Gore5, J. Larkin2
  • 1royal marsden nhs trust, sw3 6jj - london/UK
  • 2Medical Oncology, royal marsden nhs trust, sw3 6jj - london/UK
  • 3Statistics, royal marsden nhs trust, london/UK
  • 4Radiology, royal marsden nhs trust, sw3 6jj - london/UK
  • 5Department Of Medicine, royal marsden nhs trust, sw3 6jj - london/UK

Abstract

Introduction

Sunitinib is a standard 1st line treatment for advanced renal cell carcinoma (RCC) but 2/3rd of patients do not respond to treatment and the 2 weeks ‘off’ treatment is sometimes associated with tumour regrowth and recrudescence of disease symptoms. Both sunitinib and low dose metronomic cyclophosphamide (Sun-Cyclo) are anti-angiogenic therapies that act via different pathways. The possibility therefore exists that by combining these two drugs, more complete blockade of angiogenesis may be achieved.

Aims and objectives

The primary objective of the study is to evaluate the efficacy and toxicity of Sun-Cyclo. The primary endpoints are to establish the maximum tolerated dose (MTD) and the response rate (RR). The secondary endpoints are to assess the toxicity, progression-free survival (PFS) and overall survival (OS).

Patients and methods

This is a single arm, open label phase 2 study. Treatment naïve patients with ECOG 0/1 and a histological/cytological diagnosis of RCC, who were considered suitable for treatment with sunitinib were enrolled into this study. The study is being conducted in 2 parts. The objective of Stage A is to establish the MTD of Sun-Cyclo and evaluate the efficacy and toxicity of Sun-Cyclo in a small cohort (n = 19) of patients. The objective of Stage B is to further evaluate efficacy and toxicity in an expanded population (n = 35). Sun-Cyclo was given as per following schedule: Sunitinib 50mg OD (4on/2off) and cyclosphosphamide 50mg OD continuously. We report here the interim results of Stage A.

Results

A total of 19 patients have been enrolled into this study out of which 17 were evaluable for analysis. The MTD of Sun-Cyclo was 50mg Sunitinib (4on/2off) and 50mg Cyclophosphamide. The RR was: partial response 4 (25%), stable disease 10 (62.5%) and progressive disease 2 (12.5%). The median PFS was 11.0m (95% CI 7.9-14.1m) and the 1year PFS rate was 46.8%. The commonest grade 3 toxicities were fatigue (12.5%), neutropaenia (37.5%) and thrombocytopaenia (18.8%). 10 patients had dose reductions [4 (40%) had 1 dose reduction to 37.5mg and 6 (60%) had 2 dose reductions to 25mg]. 12 patients had treatment delays with a median of 7 days (range: 2–28).

Conclusion

The combination of Sun-Cyclo was relatively well tolerated. The RR and PFS with Sun-Cyclo are similar to phase III results with sunitinib alone in RCC.

Disclosure

K. Edmonds: Nil related to this research.

K. Khabra: Nil related to this research.

A. Sohaib: Nil related to this research.

K. Pennert: Nil related to this research.

L. Pickering: Pfizer: Research funding, honoraria, consultant role.

M.E. Gore: Pfizer, Speaker bureau, advisory board.

J. Larkin: Pfizer: Research funding, honoraria, consultant role.

All other authors have declared no conflicts of interest.