Phase i trial of non-cytotoxic suramin as a modulator of docetaxel and gemcitabine therapy in previously treated patients with non-small cell lung cancer

Elaine T. Lam, Jessie L.S. Au, Gregory A. Otterson, M. Guillaume Wientjes, Ling Chen, Tong Shen, Yong Wei, Xiaobai Li, Tanios Bekaii-Saab, Anthony J. Murgo, Rhonda R. Jensen, Michael Grever, Miguel A. Villalona-Calero

Research output: Contribution to journalArticle

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Abstract

Purpose: In preclinical models, non-cytotoxic suramin (concentrations <50 μM) potentiates the activity of multiple chemotherapeutic agents. The present study evaluated the safety and tolerability of suramin in combination with docetaxel or gemcitabine in previously chemotherapy-treated patients with advanced non-small cell lung cancer. Methods: Patients received suramin intravenously in combination with either docetaxel on day 1 or gemcitabine on days 1 and 8, of each 21-day treatment cycle. After 3 cycles, patients with partial response (PR) or better continued on the same combination, whereas patients with stable disease (SD) or worse crossed-over to the other combination. Pharmacokinetic analyses were performed before and after each treatment. Results: Eighteen patients received a total of 79 courses (37 suramin plus docetaxel, 42 suramin plus gemcitabine). The dose-limiting toxicity (DLT) was febrile neutropenia, observed in three of six patients treated with suramin and docetaxel 75 mg/m2. No DLTs were observed with suramin plus docetaxel 56 mg/m2 or suramin plus gemcitabine 1,250 mg/m 2. Common adverse events included neutropenia, thrombocytopenia, anemia, fatigue, nausea, vomiting, skin rash, hyperglycemia, and electrolyte abnormalities. The target plasma suramin concentration range of 10-50 μM was achieved in 90% of treatments. Discernable antitumor activity was noted in 11 patients (2 PR, 9 SD). Conclusions: Non-cytotoxic suramin, in combination with docetaxel 56 mg/m2 or gemcitabine 1,250 mg/m2, was reasonably well-tolerated with a manageable toxicity profile. Target plasma concentrations were correctly predicted by our previously described dosing nomogram. The observed preliminary evidence of antitumor activity encourages evaluation of this strategy in efficacy trials.

Original languageEnglish (US)
Pages (from-to)1019-1029
Number of pages11
JournalCancer Chemotherapy and Pharmacology
Volume66
Issue number6
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Fingerprint

docetaxel
gemcitabine
Suramin
Non-Small Cell Lung Carcinoma
Modulators
Cells
Therapeutics
Toxicity
Plasmas
Febrile Neutropenia
Nomograms
Pharmacokinetics
Chemotherapy

Keywords

  • Chemosensitizer
  • Docetaxel
  • Gemcitabine
  • Modulator
  • Non-small cell lung cancer
  • Suramin

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Phase i trial of non-cytotoxic suramin as a modulator of docetaxel and gemcitabine therapy in previously treated patients with non-small cell lung cancer. / Lam, Elaine T.; Au, Jessie L.S.; Otterson, Gregory A.; Guillaume Wientjes, M.; Chen, Ling; Shen, Tong; Wei, Yong; Li, Xiaobai; Bekaii-Saab, Tanios; Murgo, Anthony J.; Jensen, Rhonda R.; Grever, Michael; Villalona-Calero, Miguel A.

In: Cancer Chemotherapy and Pharmacology, Vol. 66, No. 6, 01.11.2010, p. 1019-1029.

Research output: Contribution to journalArticle

Lam, ET, Au, JLS, Otterson, GA, Guillaume Wientjes, M, Chen, L, Shen, T, Wei, Y, Li, X, Bekaii-Saab, T, Murgo, AJ, Jensen, RR, Grever, M & Villalona-Calero, MA 2010, 'Phase i trial of non-cytotoxic suramin as a modulator of docetaxel and gemcitabine therapy in previously treated patients with non-small cell lung cancer', Cancer Chemotherapy and Pharmacology, vol. 66, no. 6, pp. 1019-1029. https://doi.org/10.1007/s00280-010-1252-x
Lam, Elaine T. ; Au, Jessie L.S. ; Otterson, Gregory A. ; Guillaume Wientjes, M. ; Chen, Ling ; Shen, Tong ; Wei, Yong ; Li, Xiaobai ; Bekaii-Saab, Tanios ; Murgo, Anthony J. ; Jensen, Rhonda R. ; Grever, Michael ; Villalona-Calero, Miguel A. / Phase i trial of non-cytotoxic suramin as a modulator of docetaxel and gemcitabine therapy in previously treated patients with non-small cell lung cancer. In: Cancer Chemotherapy and Pharmacology. 2010 ; Vol. 66, No. 6. pp. 1019-1029.
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abstract = "Purpose: In preclinical models, non-cytotoxic suramin (concentrations <50 μM) potentiates the activity of multiple chemotherapeutic agents. The present study evaluated the safety and tolerability of suramin in combination with docetaxel or gemcitabine in previously chemotherapy-treated patients with advanced non-small cell lung cancer. Methods: Patients received suramin intravenously in combination with either docetaxel on day 1 or gemcitabine on days 1 and 8, of each 21-day treatment cycle. After 3 cycles, patients with partial response (PR) or better continued on the same combination, whereas patients with stable disease (SD) or worse crossed-over to the other combination. Pharmacokinetic analyses were performed before and after each treatment. Results: Eighteen patients received a total of 79 courses (37 suramin plus docetaxel, 42 suramin plus gemcitabine). The dose-limiting toxicity (DLT) was febrile neutropenia, observed in three of six patients treated with suramin and docetaxel 75 mg/m2. No DLTs were observed with suramin plus docetaxel 56 mg/m2 or suramin plus gemcitabine 1,250 mg/m 2. Common adverse events included neutropenia, thrombocytopenia, anemia, fatigue, nausea, vomiting, skin rash, hyperglycemia, and electrolyte abnormalities. The target plasma suramin concentration range of 10-50 μM was achieved in 90{\%} of treatments. Discernable antitumor activity was noted in 11 patients (2 PR, 9 SD). Conclusions: Non-cytotoxic suramin, in combination with docetaxel 56 mg/m2 or gemcitabine 1,250 mg/m2, was reasonably well-tolerated with a manageable toxicity profile. Target plasma concentrations were correctly predicted by our previously described dosing nomogram. The observed preliminary evidence of antitumor activity encourages evaluation of this strategy in efficacy trials.",
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T1 - Phase i trial of non-cytotoxic suramin as a modulator of docetaxel and gemcitabine therapy in previously treated patients with non-small cell lung cancer

AU - Lam, Elaine T.

AU - Au, Jessie L.S.

AU - Otterson, Gregory A.

AU - Guillaume Wientjes, M.

AU - Chen, Ling

AU - Shen, Tong

AU - Wei, Yong

AU - Li, Xiaobai

AU - Bekaii-Saab, Tanios

AU - Murgo, Anthony J.

AU - Jensen, Rhonda R.

AU - Grever, Michael

AU - Villalona-Calero, Miguel A.

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N2 - Purpose: In preclinical models, non-cytotoxic suramin (concentrations <50 μM) potentiates the activity of multiple chemotherapeutic agents. The present study evaluated the safety and tolerability of suramin in combination with docetaxel or gemcitabine in previously chemotherapy-treated patients with advanced non-small cell lung cancer. Methods: Patients received suramin intravenously in combination with either docetaxel on day 1 or gemcitabine on days 1 and 8, of each 21-day treatment cycle. After 3 cycles, patients with partial response (PR) or better continued on the same combination, whereas patients with stable disease (SD) or worse crossed-over to the other combination. Pharmacokinetic analyses were performed before and after each treatment. Results: Eighteen patients received a total of 79 courses (37 suramin plus docetaxel, 42 suramin plus gemcitabine). The dose-limiting toxicity (DLT) was febrile neutropenia, observed in three of six patients treated with suramin and docetaxel 75 mg/m2. No DLTs were observed with suramin plus docetaxel 56 mg/m2 or suramin plus gemcitabine 1,250 mg/m 2. Common adverse events included neutropenia, thrombocytopenia, anemia, fatigue, nausea, vomiting, skin rash, hyperglycemia, and electrolyte abnormalities. The target plasma suramin concentration range of 10-50 μM was achieved in 90% of treatments. Discernable antitumor activity was noted in 11 patients (2 PR, 9 SD). Conclusions: Non-cytotoxic suramin, in combination with docetaxel 56 mg/m2 or gemcitabine 1,250 mg/m2, was reasonably well-tolerated with a manageable toxicity profile. Target plasma concentrations were correctly predicted by our previously described dosing nomogram. The observed preliminary evidence of antitumor activity encourages evaluation of this strategy in efficacy trials.

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