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, Tanios 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

26 Citations (Scopus)

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 - Nov 3 2008
Externally publishedYes

Fingerprint

Suramin
Non-Small Cell Lung Carcinoma
Paclitaxel
Carboplatin
Survival Rate
Drug Therapy
Nomograms
Survival
Poisons
Fibroblast Growth Factor 2
Random Allocation
Protein-Tyrosine Kinases
Disease-Free Survival
Sequence Analysis
Survivors
Pharmacokinetics
Adenosine Triphosphate
Confidence Intervals

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Villalona-Calero, M. A., Otterson, G. A., Wientjes, M. G., Weber, F., Bekaii-Saab, T., Young, D., ... Au, J. L. S. (2008). Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer: A phase II study. Annals of Oncology, 19(11), 1903-1909. https://doi.org/10.1093/annonc/mdn412

Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer : A phase II study. / Villalona-Calero, Miguel A.; Otterson, G. A.; Wientjes, M. G.; Weber, F.; Bekaii-Saab, Tanios; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. K.; Wei, Y.; Zhang, Y.; Eng, C.; Grever, M.; Au, J. L.S.

In: Annals of Oncology, Vol. 19, No. 11, 03.11.2008, p. 1903-1909.

Research output: Contribution to journalArticle

Villalona-Calero, MA, Otterson, GA, Wientjes, MG, Weber, F, Bekaii-Saab, T, Young, D, Murgo, AJ, Jensen, R, Yeh, TK, Wei, Y, Zhang, Y, Eng, C, Grever, M & Au, JLS 2008, 'Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer: A phase II study', Annals of Oncology, vol. 19, no. 11, pp. 1903-1909. https://doi.org/10.1093/annonc/mdn412
Villalona-Calero, Miguel A. ; Otterson, G. A. ; Wientjes, M. G. ; Weber, F. ; Bekaii-Saab, Tanios ; Young, D. ; Murgo, A. J. ; Jensen, R. ; Yeh, T. K. ; Wei, Y. ; Zhang, Y. ; Eng, C. ; Grever, M. ; Au, J. L.S. / Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer : A phase II study. In: Annals of Oncology. 2008 ; Vol. 19, No. 11. pp. 1903-1909.
@article{78866b7dcf7948b294c6bc3f55646234,
title = "Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer: A phase II study",
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.",
keywords = "Chemosensitization, Drug resistance, FGF, Lung cancer, Suramin",
author = "Villalona-Calero, {Miguel A.} and Otterson, {G. A.} and Wientjes, {M. G.} and F. Weber and Tanios Bekaii-Saab and D. Young and Murgo, {A. J.} and R. Jensen and Yeh, {T. K.} and Y. Wei and Y. Zhang and C. Eng and M. Grever and Au, {J. L.S.}",
year = "2008",
month = "11",
day = "3",
doi = "10.1093/annonc/mdn412",
language = "English (US)",
volume = "19",
pages = "1903--1909",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer

T2 - A phase II study

AU - Villalona-Calero, Miguel A.

AU - Otterson, G. A.

AU - Wientjes, M. G.

AU - Weber, F.

AU - Bekaii-Saab, Tanios

AU - Young, D.

AU - Murgo, A. J.

AU - Jensen, R.

AU - Yeh, T. K.

AU - Wei, Y.

AU - Zhang, Y.

AU - Eng, C.

AU - Grever, M.

AU - Au, J. L.S.

PY - 2008/11/3

Y1 - 2008/11/3

N2 - 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.

AB - 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.

KW - Chemosensitization

KW - Drug resistance

KW - FGF

KW - Lung cancer

KW - Suramin

UR - http://www.scopus.com/inward/record.url?scp=54949146895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54949146895&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdn412

DO - 10.1093/annonc/mdn412

M3 - Article

C2 - 18632723

AN - SCOPUS:54949146895

VL - 19

SP - 1903

EP - 1909

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 11

ER -