Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma: Results of a randomised Phase 2 study

Donald Richards, Darren M. Kocs, Alexander Spira, A. David McCollum, Sami Diab, Lanny I. Hecker, Allen Cohn, Feng Zhan, Lina Asmar

Research output: Contribution to journalArticle

Abstract

Patients with advanced adenocarcinoma of the gastroesophageal junction/stomach are treated by combination chemotherapy, with minimal improvements in survival. We evaluated adding cetuximab to combination chemotherapy in these patients. Methods The primary objective was progression-free survival. Secondary objectives were response rate, time to response, duration of response and safety. Treatment Arm 1: docetaxel + oxaliplatin (DOCOX) = docetaxel 60 mg/m2 plus oxaliplatin 130 mg/m2 on Day 1 of each 21-day cycle. Arm 2: docetaxel + oxaliplatin + cetuximab (DOCOX + C) = DOCOX with C 400 mg/m2 first dose then 250 mg/m2 weekly. The protocol was amended to allow collection of tissue to correlate responses with KRAS status. Findings One hundred fifty patients were enrolled (75/arm). DOCOX/DOCOX + C: gastric 44%/41%, gastroesophageal junction 51%/55%, both 5%/4%. Response rate/arm: 26.5%/38.0%. Median progression-free survival: 4.7/5.1 months (95% confidence interval (CI) 3.0-5.6/4.3-5.9); 1 year survival: 39.1%/33.0%, median overall survival: 8.5/9.4 months; median duration of response: 7.3/5.6 months. Grade 3-4 treatment-related adverse events (%) included neutropenia (50%/44%), febrile neutropenia (13%/19%), diarrhoea (12%/17%), fatigue (12%/17%) and leukopenia (7%/14%). Discontinuation was due to progressive disease 39/32 and adverse events 21/34. KRAS was collected on some patients 2 years into the study because of new American Society of Clinical Oncology (ASCO) findings. Interpretation Cetuximab added to DOCOX may improve response rate minimally; there appears to be no improvement in progression-free survival, overall survival or 1-year survival. Cetuximab added to DOCOX did not produce clinically significant outcomes. Toxicities were consistent with the study drugs' known safety profiles. KRAS mutation was infrequent; no conclusions can be drawn from KRAS response data. ClinicalTrial.gov Identifier: NCT00517829.

Original languageEnglish (US)
Pages (from-to)2823-2831
Number of pages9
JournalEuropean Journal of Cancer
Volume49
Issue number13
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

oxaliplatin
docetaxel
Esophagogastric Junction
Stomach
Adenocarcinoma
Survival
Disease-Free Survival
Combination Drug Therapy
Safety
Febrile Neutropenia
Cetuximab
Leukopenia
Neutropenia

Keywords

  • Adenocarcinoma
  • Drug therapy
  • Gastroesophageal junction
  • KRAS

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma : Results of a randomised Phase 2 study. / Richards, Donald; Kocs, Darren M.; Spira, Alexander; David McCollum, A.; Diab, Sami; Hecker, Lanny I.; Cohn, Allen; Zhan, Feng; Asmar, Lina.

In: European Journal of Cancer, Vol. 49, No. 13, 01.09.2013, p. 2823-2831.

Research output: Contribution to journalArticle

Richards, Donald ; Kocs, Darren M. ; Spira, Alexander ; David McCollum, A. ; Diab, Sami ; Hecker, Lanny I. ; Cohn, Allen ; Zhan, Feng ; Asmar, Lina. / Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma : Results of a randomised Phase 2 study. In: European Journal of Cancer. 2013 ; Vol. 49, No. 13. pp. 2823-2831.
@article{b44907378d794af188bd113e71bdf112,
title = "Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma: Results of a randomised Phase 2 study",
abstract = "Patients with advanced adenocarcinoma of the gastroesophageal junction/stomach are treated by combination chemotherapy, with minimal improvements in survival. We evaluated adding cetuximab to combination chemotherapy in these patients. Methods The primary objective was progression-free survival. Secondary objectives were response rate, time to response, duration of response and safety. Treatment Arm 1: docetaxel + oxaliplatin (DOCOX) = docetaxel 60 mg/m2 plus oxaliplatin 130 mg/m2 on Day 1 of each 21-day cycle. Arm 2: docetaxel + oxaliplatin + cetuximab (DOCOX + C) = DOCOX with C 400 mg/m2 first dose then 250 mg/m2 weekly. The protocol was amended to allow collection of tissue to correlate responses with KRAS status. Findings One hundred fifty patients were enrolled (75/arm). DOCOX/DOCOX + C: gastric 44{\%}/41{\%}, gastroesophageal junction 51{\%}/55{\%}, both 5{\%}/4{\%}. Response rate/arm: 26.5{\%}/38.0{\%}. Median progression-free survival: 4.7/5.1 months (95{\%} confidence interval (CI) 3.0-5.6/4.3-5.9); 1 year survival: 39.1{\%}/33.0{\%}, median overall survival: 8.5/9.4 months; median duration of response: 7.3/5.6 months. Grade 3-4 treatment-related adverse events ({\%}) included neutropenia (50{\%}/44{\%}), febrile neutropenia (13{\%}/19{\%}), diarrhoea (12{\%}/17{\%}), fatigue (12{\%}/17{\%}) and leukopenia (7{\%}/14{\%}). Discontinuation was due to progressive disease 39/32 and adverse events 21/34. KRAS was collected on some patients 2 years into the study because of new American Society of Clinical Oncology (ASCO) findings. Interpretation Cetuximab added to DOCOX may improve response rate minimally; there appears to be no improvement in progression-free survival, overall survival or 1-year survival. Cetuximab added to DOCOX did not produce clinically significant outcomes. Toxicities were consistent with the study drugs' known safety profiles. KRAS mutation was infrequent; no conclusions can be drawn from KRAS response data. ClinicalTrial.gov Identifier: NCT00517829.",
keywords = "Adenocarcinoma, Drug therapy, Gastroesophageal junction, KRAS",
author = "Donald Richards and Kocs, {Darren M.} and Alexander Spira and {David McCollum}, A. and Sami Diab and Hecker, {Lanny I.} and Allen Cohn and Feng Zhan and Lina Asmar",
year = "2013",
month = "9",
day = "1",
doi = "10.1016/j.ejca.2013.04.022",
language = "English (US)",
volume = "49",
pages = "2823--2831",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "13",

}

TY - JOUR

T1 - Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma

T2 - Results of a randomised Phase 2 study

AU - Richards, Donald

AU - Kocs, Darren M.

AU - Spira, Alexander

AU - David McCollum, A.

AU - Diab, Sami

AU - Hecker, Lanny I.

AU - Cohn, Allen

AU - Zhan, Feng

AU - Asmar, Lina

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Patients with advanced adenocarcinoma of the gastroesophageal junction/stomach are treated by combination chemotherapy, with minimal improvements in survival. We evaluated adding cetuximab to combination chemotherapy in these patients. Methods The primary objective was progression-free survival. Secondary objectives were response rate, time to response, duration of response and safety. Treatment Arm 1: docetaxel + oxaliplatin (DOCOX) = docetaxel 60 mg/m2 plus oxaliplatin 130 mg/m2 on Day 1 of each 21-day cycle. Arm 2: docetaxel + oxaliplatin + cetuximab (DOCOX + C) = DOCOX with C 400 mg/m2 first dose then 250 mg/m2 weekly. The protocol was amended to allow collection of tissue to correlate responses with KRAS status. Findings One hundred fifty patients were enrolled (75/arm). DOCOX/DOCOX + C: gastric 44%/41%, gastroesophageal junction 51%/55%, both 5%/4%. Response rate/arm: 26.5%/38.0%. Median progression-free survival: 4.7/5.1 months (95% confidence interval (CI) 3.0-5.6/4.3-5.9); 1 year survival: 39.1%/33.0%, median overall survival: 8.5/9.4 months; median duration of response: 7.3/5.6 months. Grade 3-4 treatment-related adverse events (%) included neutropenia (50%/44%), febrile neutropenia (13%/19%), diarrhoea (12%/17%), fatigue (12%/17%) and leukopenia (7%/14%). Discontinuation was due to progressive disease 39/32 and adverse events 21/34. KRAS was collected on some patients 2 years into the study because of new American Society of Clinical Oncology (ASCO) findings. Interpretation Cetuximab added to DOCOX may improve response rate minimally; there appears to be no improvement in progression-free survival, overall survival or 1-year survival. Cetuximab added to DOCOX did not produce clinically significant outcomes. Toxicities were consistent with the study drugs' known safety profiles. KRAS mutation was infrequent; no conclusions can be drawn from KRAS response data. ClinicalTrial.gov Identifier: NCT00517829.

AB - Patients with advanced adenocarcinoma of the gastroesophageal junction/stomach are treated by combination chemotherapy, with minimal improvements in survival. We evaluated adding cetuximab to combination chemotherapy in these patients. Methods The primary objective was progression-free survival. Secondary objectives were response rate, time to response, duration of response and safety. Treatment Arm 1: docetaxel + oxaliplatin (DOCOX) = docetaxel 60 mg/m2 plus oxaliplatin 130 mg/m2 on Day 1 of each 21-day cycle. Arm 2: docetaxel + oxaliplatin + cetuximab (DOCOX + C) = DOCOX with C 400 mg/m2 first dose then 250 mg/m2 weekly. The protocol was amended to allow collection of tissue to correlate responses with KRAS status. Findings One hundred fifty patients were enrolled (75/arm). DOCOX/DOCOX + C: gastric 44%/41%, gastroesophageal junction 51%/55%, both 5%/4%. Response rate/arm: 26.5%/38.0%. Median progression-free survival: 4.7/5.1 months (95% confidence interval (CI) 3.0-5.6/4.3-5.9); 1 year survival: 39.1%/33.0%, median overall survival: 8.5/9.4 months; median duration of response: 7.3/5.6 months. Grade 3-4 treatment-related adverse events (%) included neutropenia (50%/44%), febrile neutropenia (13%/19%), diarrhoea (12%/17%), fatigue (12%/17%) and leukopenia (7%/14%). Discontinuation was due to progressive disease 39/32 and adverse events 21/34. KRAS was collected on some patients 2 years into the study because of new American Society of Clinical Oncology (ASCO) findings. Interpretation Cetuximab added to DOCOX may improve response rate minimally; there appears to be no improvement in progression-free survival, overall survival or 1-year survival. Cetuximab added to DOCOX did not produce clinically significant outcomes. Toxicities were consistent with the study drugs' known safety profiles. KRAS mutation was infrequent; no conclusions can be drawn from KRAS response data. ClinicalTrial.gov Identifier: NCT00517829.

KW - Adenocarcinoma

KW - Drug therapy

KW - Gastroesophageal junction

KW - KRAS

UR - http://www.scopus.com/inward/record.url?scp=84881099408&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881099408&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2013.04.022

DO - 10.1016/j.ejca.2013.04.022

M3 - Article

C2 - 23747051

AN - SCOPUS:84881099408

VL - 49

SP - 2823

EP - 2831

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 13

ER -