Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer

A multicenter phase 2 study

Chandra Belani, Marshall T. Schreeder, Ronald G. Steis, Richard A. Guidice, Thomas A. Marsland, Elizabeth H. Butler, Suresh S. Ramalingam

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

BACKGROUND. Cetuximab, an immunoglobulin (Ig) G1 chimeric monoclonal antibody against the epidermal growth factor receptor, has demonstrated evidence of activity in nonsmall cell lung cancer (NSCLC). When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab has exhibited synergistic interaction in preclinical studies. Therefore, a phase 2 study was conducted to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. METHODS. Chemotherapy-naïve patients aged ≥18 years with stage IIIB (with effusion) or stage IV NSCLC received cetuximab (at a dose of 400 mg/m2 on Day 1 and 250 mg/m2 on Days 8 and 15) plus docetaxel (at a dose of 75 mg/m2 on Day 1) and carboplatin (area under the concentration vs time curve [AUC] = 6 on Day 1) every 21 days for up to 6 cycles (graded according to the American Joint Committee on Cancer Staging System). Thereafter, patients without evidence of disease progression were continued on single-agent cetuximab for a maximum of 1 year or until disease progression. The primary endpoint was response rate. RESULTS. Eighty patients were enrolled. The median number of cycles administered was 4 (range, 1-6 cycles). The objective response rate was 15.2%, with a median progression-free survival of 4.6 months and a median overall survival of 10.3 months. The salient grades 3 of 4 adverse events were neutropenia (30%), hypotension (3%), hypokalemia (4%), and hypomagnesemia (3%). Twenty-five patients received single-agent cetuximab (median duration, 12 weeks) and this was well tolerated. CONCLUSIONS. The results of this large, multicenter, phase 3 study indicate that the novel combination of cetuximab with docetaxel and carboplatin demonstrate modest anticancer activity for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile.

Original languageEnglish (US)
Pages (from-to)2512-2517
Number of pages6
JournalCancer
Volume113
Issue number9
DOIs
StatePublished - Nov 1 2008

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docetaxel
Carboplatin
Non-Small Cell Lung Carcinoma
Disease Progression
Hypokalemia
Neoplasm Staging
Cetuximab
Neutropenia
Epidermal Growth Factor Receptor
Hypotension
Disease-Free Survival
Area Under Curve
Immunoglobulins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Belani, Chandra ; Schreeder, Marshall T. ; Steis, Ronald G. ; Guidice, Richard A. ; Marsland, Thomas A. ; Butler, Elizabeth H. ; Ramalingam, Suresh S. / Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer : A multicenter phase 2 study. In: Cancer. 2008 ; Vol. 113, No. 9. pp. 2512-2517.
@article{e295433fd0b94a25a1953dcf441dcd4a,
title = "Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: A multicenter phase 2 study",
abstract = "BACKGROUND. Cetuximab, an immunoglobulin (Ig) G1 chimeric monoclonal antibody against the epidermal growth factor receptor, has demonstrated evidence of activity in nonsmall cell lung cancer (NSCLC). When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab has exhibited synergistic interaction in preclinical studies. Therefore, a phase 2 study was conducted to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. METHODS. Chemotherapy-na{\"i}ve patients aged ≥18 years with stage IIIB (with effusion) or stage IV NSCLC received cetuximab (at a dose of 400 mg/m2 on Day 1 and 250 mg/m2 on Days 8 and 15) plus docetaxel (at a dose of 75 mg/m2 on Day 1) and carboplatin (area under the concentration vs time curve [AUC] = 6 on Day 1) every 21 days for up to 6 cycles (graded according to the American Joint Committee on Cancer Staging System). Thereafter, patients without evidence of disease progression were continued on single-agent cetuximab for a maximum of 1 year or until disease progression. The primary endpoint was response rate. RESULTS. Eighty patients were enrolled. The median number of cycles administered was 4 (range, 1-6 cycles). The objective response rate was 15.2{\%}, with a median progression-free survival of 4.6 months and a median overall survival of 10.3 months. The salient grades 3 of 4 adverse events were neutropenia (30{\%}), hypotension (3{\%}), hypokalemia (4{\%}), and hypomagnesemia (3{\%}). Twenty-five patients received single-agent cetuximab (median duration, 12 weeks) and this was well tolerated. CONCLUSIONS. The results of this large, multicenter, phase 3 study indicate that the novel combination of cetuximab with docetaxel and carboplatin demonstrate modest anticancer activity for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile.",
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Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer : A multicenter phase 2 study. / Belani, Chandra; Schreeder, Marshall T.; Steis, Ronald G.; Guidice, Richard A.; Marsland, Thomas A.; Butler, Elizabeth H.; Ramalingam, Suresh S.

In: Cancer, Vol. 113, No. 9, 01.11.2008, p. 2512-2517.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer

T2 - A multicenter phase 2 study

AU - Belani, Chandra

AU - Schreeder, Marshall T.

AU - Steis, Ronald G.

AU - Guidice, Richard A.

AU - Marsland, Thomas A.

AU - Butler, Elizabeth H.

AU - Ramalingam, Suresh S.

PY - 2008/11/1

Y1 - 2008/11/1

N2 - BACKGROUND. Cetuximab, an immunoglobulin (Ig) G1 chimeric monoclonal antibody against the epidermal growth factor receptor, has demonstrated evidence of activity in nonsmall cell lung cancer (NSCLC). When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab has exhibited synergistic interaction in preclinical studies. Therefore, a phase 2 study was conducted to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. METHODS. Chemotherapy-naïve patients aged ≥18 years with stage IIIB (with effusion) or stage IV NSCLC received cetuximab (at a dose of 400 mg/m2 on Day 1 and 250 mg/m2 on Days 8 and 15) plus docetaxel (at a dose of 75 mg/m2 on Day 1) and carboplatin (area under the concentration vs time curve [AUC] = 6 on Day 1) every 21 days for up to 6 cycles (graded according to the American Joint Committee on Cancer Staging System). Thereafter, patients without evidence of disease progression were continued on single-agent cetuximab for a maximum of 1 year or until disease progression. The primary endpoint was response rate. RESULTS. Eighty patients were enrolled. The median number of cycles administered was 4 (range, 1-6 cycles). The objective response rate was 15.2%, with a median progression-free survival of 4.6 months and a median overall survival of 10.3 months. The salient grades 3 of 4 adverse events were neutropenia (30%), hypotension (3%), hypokalemia (4%), and hypomagnesemia (3%). Twenty-five patients received single-agent cetuximab (median duration, 12 weeks) and this was well tolerated. CONCLUSIONS. The results of this large, multicenter, phase 3 study indicate that the novel combination of cetuximab with docetaxel and carboplatin demonstrate modest anticancer activity for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile.

AB - BACKGROUND. Cetuximab, an immunoglobulin (Ig) G1 chimeric monoclonal antibody against the epidermal growth factor receptor, has demonstrated evidence of activity in nonsmall cell lung cancer (NSCLC). When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab has exhibited synergistic interaction in preclinical studies. Therefore, a phase 2 study was conducted to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. METHODS. Chemotherapy-naïve patients aged ≥18 years with stage IIIB (with effusion) or stage IV NSCLC received cetuximab (at a dose of 400 mg/m2 on Day 1 and 250 mg/m2 on Days 8 and 15) plus docetaxel (at a dose of 75 mg/m2 on Day 1) and carboplatin (area under the concentration vs time curve [AUC] = 6 on Day 1) every 21 days for up to 6 cycles (graded according to the American Joint Committee on Cancer Staging System). Thereafter, patients without evidence of disease progression were continued on single-agent cetuximab for a maximum of 1 year or until disease progression. The primary endpoint was response rate. RESULTS. Eighty patients were enrolled. The median number of cycles administered was 4 (range, 1-6 cycles). The objective response rate was 15.2%, with a median progression-free survival of 4.6 months and a median overall survival of 10.3 months. The salient grades 3 of 4 adverse events were neutropenia (30%), hypotension (3%), hypokalemia (4%), and hypomagnesemia (3%). Twenty-five patients received single-agent cetuximab (median duration, 12 weeks) and this was well tolerated. CONCLUSIONS. The results of this large, multicenter, phase 3 study indicate that the novel combination of cetuximab with docetaxel and carboplatin demonstrate modest anticancer activity for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile.

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