Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer: A phase II study

Miguel A. Villalona-Calero, G. A. Otterson, M. G. Wientjes, F. Weber, T. Bekaii-Saab, D. Young, A. J. Murgo, R. Jensen, T. K. Yeh, Y. Wei, Y. Zhang, C. Eng, M. Grever, J. L.S. Au

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background: The purpose of this study was to evaluate the potential of noncytotoxic doses of suramin to reverse chemotherapy resistance in advanced chemonaive and chemoresistant non-small-cell lung cancer patients. Patients and methods: Patients received paclitaxel (Taxol) (200 mg/m2) and carboplatin (area under the concentration-time curve 6 mg/ml/min) every 3 weeks. The total suramin per cycle dose was calculated using a nomogram derived from the preceding phase I trial to obtain the desirable plasma concentration range of 10-50 μM. Results: Thirty-nine response-assessable chemonaive patients (arm A) received 213 cycles. Thirty-eight cycles were administered to 15 patients with demonstrated resistance to paclitaxel and carboplatin (arm B). The pattern/frequency of toxic effects was similar to those expected for paclitaxel/carboplatin, and pharmacokinetic analyses (199 cycles) showed suramin plasma concentrations maintained between 10 and 50 μM in 94% of cycles. In arm A, response evaluation criteria in solid tumors (RECIST) response rate was 36% (95% confidence interval 22% to 54%; two complete, 12 partial); 15 patients (38%) had disease stabilization for ≥4 months; median progression-free survival (intention to treat) was 6.4 months; median overall survival (OS) 10.4 months and 1-year survival rate 38%. In arm B, no RECIST responses occurred; four patients had disease stabilization for ≥4 months; median OS was 132 days and 1-year survival rate 7%. Plasma basic fibroblast growth factor levels were higher in chemopretreated/refractory patients compared with chemonaive patients (P = 0.05). Sequence analysis of the EGFR tyrosine kinase domain in a long-term disease-free survivor revealed an ATP-binding pocket mutation (T790M). Conclusions: Noncytotoxic suramin did not increase paclitaxel/ carboplatin's toxicity and the suramin dose was predicted from clinical parameters. No clinically significant reversal of primary resistance was documented, but a modulatory effect in chemotherapy-naive patients cannot be excluded. Controlled randomization is planned for further evaluation of this treatment strategy.

Original languageEnglish (US)
Pages (from-to)1903-1909
Number of pages7
JournalAnnals of Oncology
Volume19
Issue number11
DOIs
StatePublished - 2008

Keywords

  • Chemosensitization
  • Drug resistance
  • FGF
  • Lung cancer
  • Suramin

ASJC Scopus subject areas

  • Hematology
  • Oncology

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