A phase I/II study of GTI-2040 plus docetaxel as second-line treatment in advanced non-small cell lung cancer

A study of the PMH phase II consortium

Natasha B. Leighl, Scott A. Laurie, Xueyu E. Chen, Peter Ellis, Frances A. Shepherd, Jennifer J. Knox, Glenwood Goss, Ronald L. Burkes, Gregory R. Pond, Christopher Dick, Yun Yen, James A. Zwiebel, Malcolm J. Moore

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

INTRODUCTION: GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase II dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and 1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days. RESULTS: Twenty-nine patients were treated, (24 NSCLC, 3 hormone-refractory prostate cancer, 1 head and neck, and 1 small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m intravenously every 21days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase I, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D. CONCLUSIONS: Activity of the combination at RP2D, GTI-2040 5 mg/kg/d × 14 days by CVI plus docetaxel 75 mg/m does not seem superior to docetaxel alone in previously treated NSCLC.

Original languageEnglish
Pages (from-to)1163-1169
Number of pages7
JournalJournal of Thoracic Oncology
Volume4
Issue number9
DOIs
Publication statusPublished - Jan 1 2009
Externally publishedYes

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docetaxel
Non-Small Cell Lung Carcinoma
Intravenous Infusions
Therapeutics
Febrile Neutropenia
Antisense Oligonucleotides
Small Cell Lung Carcinoma
Prostate-Specific Antigen
Head and Neck Neoplasms
Platinum
GTI2040
Neoplasms
Prostatic Neoplasms
Central Nervous System
Bone Marrow
Hormones
Neoplasm Metastasis

Keywords

  • Antisense oligonucleotide
  • Docetaxel
  • GTI-2040
  • Lung cancer
  • R2 subunit
  • Ribonucleotide reductase
  • Second-line

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

A phase I/II study of GTI-2040 plus docetaxel as second-line treatment in advanced non-small cell lung cancer : A study of the PMH phase II consortium. / Leighl, Natasha B.; Laurie, Scott A.; Chen, Xueyu E.; Ellis, Peter; Shepherd, Frances A.; Knox, Jennifer J.; Goss, Glenwood; Burkes, Ronald L.; Pond, Gregory R.; Dick, Christopher; Yen, Yun; Zwiebel, James A.; Moore, Malcolm J.

In: Journal of Thoracic Oncology, Vol. 4, No. 9, 01.01.2009, p. 1163-1169.

Research output: Contribution to journalArticle

Leighl, NB, Laurie, SA, Chen, XE, Ellis, P, Shepherd, FA, Knox, JJ, Goss, G, Burkes, RL, Pond, GR, Dick, C, Yen, Y, Zwiebel, JA & Moore, MJ 2009, 'A phase I/II study of GTI-2040 plus docetaxel as second-line treatment in advanced non-small cell lung cancer: A study of the PMH phase II consortium', Journal of Thoracic Oncology, vol. 4, no. 9, pp. 1163-1169. https://doi.org/10.1097/JTO.0b013e3181a949b2
Leighl, Natasha B. ; Laurie, Scott A. ; Chen, Xueyu E. ; Ellis, Peter ; Shepherd, Frances A. ; Knox, Jennifer J. ; Goss, Glenwood ; Burkes, Ronald L. ; Pond, Gregory R. ; Dick, Christopher ; Yen, Yun ; Zwiebel, James A. ; Moore, Malcolm J. / A phase I/II study of GTI-2040 plus docetaxel as second-line treatment in advanced non-small cell lung cancer : A study of the PMH phase II consortium. In: Journal of Thoracic Oncology. 2009 ; Vol. 4, No. 9. pp. 1163-1169.
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abstract = "INTRODUCTION: GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase II dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and 1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days. RESULTS: Twenty-nine patients were treated, (24 NSCLC, 3 hormone-refractory prostate cancer, 1 head and neck, and 1 small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m intravenously every 21days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase I, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D. CONCLUSIONS: Activity of the combination at RP2D, GTI-2040 5 mg/kg/d × 14 days by CVI plus docetaxel 75 mg/m does not seem superior to docetaxel alone in previously treated NSCLC.",
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AU - Laurie, Scott A.

AU - Chen, Xueyu E.

AU - Ellis, Peter

AU - Shepherd, Frances A.

AU - Knox, Jennifer J.

AU - Goss, Glenwood

AU - Burkes, Ronald L.

AU - Pond, Gregory R.

AU - Dick, Christopher

AU - Yen, Yun

AU - Zwiebel, James A.

AU - Moore, Malcolm J.

PY - 2009/1/1

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N2 - INTRODUCTION: GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase II dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and 1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days. RESULTS: Twenty-nine patients were treated, (24 NSCLC, 3 hormone-refractory prostate cancer, 1 head and neck, and 1 small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m intravenously every 21days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase I, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D. CONCLUSIONS: Activity of the combination at RP2D, GTI-2040 5 mg/kg/d × 14 days by CVI plus docetaxel 75 mg/m does not seem superior to docetaxel alone in previously treated NSCLC.

AB - INTRODUCTION: GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase II dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and 1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days. RESULTS: Twenty-nine patients were treated, (24 NSCLC, 3 hormone-refractory prostate cancer, 1 head and neck, and 1 small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m intravenously every 21days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase I, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D. CONCLUSIONS: Activity of the combination at RP2D, GTI-2040 5 mg/kg/d × 14 days by CVI plus docetaxel 75 mg/m does not seem superior to docetaxel alone in previously treated NSCLC.

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