Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma

A Phase II Study with Long-Term Follow-Up

Ari Joseph Rosenberg*, Alfred W Rademaker, Howard S. Hochster, Theresa Ryan, Thomas Hensing, Veena Shankaran, Lisa Baddi, Devalingam Mahalingam, Mary Frances Mulcahy, Al B. Benson

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Lessons Learned: Adding docetaxel to the modified FOLFOX7 backbone (DOF) is a feasible three-drug combination therapy for advanced gastric cancer with high activity, providing evidence that leucovorin is not necessary in this setting. The DOF regimen represents an alternative to the FLOT (5-FU 2,600 mg/m2 as 24-hour infusion with leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2) regimen that can be considered in select patients with advanced gastric cancer and is a potential choice in the curative setting. Background: The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity. Given the efficacy of platinum-taxane-fluoropyrimidine regimens, this phase II study evaluated the efficacy and toxicity of docetaxel, oxaliplatin, and 5-FU (DOF) for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: Patients with metastatic or unresectable gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease received docetaxel 50 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, and 5-FU 2,400 mg/m2 continuous intravenous infusion over 46 hours; cycles were repeated every 2 weeks. The primary endpoint was overall response rate (ORR). Results: Forty-four patients were enrolled. Assessment of treatment response and toxicity was feasible in 41 and 43 patients, respectively. ORR was 73.2% (68.3% partial response; 4.9% complete response). Therapy was discontinued for progressive disease in 53%, toxicity in 26%, and death on treatment in 16%. Two patients underwent surgical resection. Thirty-three patients (76.7%) received at least seven cycles (7–34). Grade 3–4 toxicities occurred in 31 patients (72.1%), including neutropenia (23.3%), neurologic (20.9%), and diarrhea (14.0%). Median overall survival was 10.3 months. Conclusion: DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an option for select patients with unresectable or metastatic gastric or GEJ adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)1039-e642
JournalOncologist
Volume24
Issue number8
DOIs
StatePublished - Jan 1 2019

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oxaliplatin
docetaxel
Esophagogastric Junction
Fluorouracil
Stomach
Adenocarcinoma
Stomach Neoplasms
Leucovorin
Therapeutics
Survival
Combination Drug Therapy
Neutropenia
Platinum
Intravenous Infusions

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rosenberg, Ari Joseph ; Rademaker, Alfred W ; Hochster, Howard S. ; Ryan, Theresa ; Hensing, Thomas ; Shankaran, Veena ; Baddi, Lisa ; Mahalingam, Devalingam ; Mulcahy, Mary Frances ; Benson, Al B. / Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma : A Phase II Study with Long-Term Follow-Up. In: Oncologist. 2019 ; Vol. 24, No. 8. pp. 1039-e642.
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title = "Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Study with Long-Term Follow-Up",
abstract = "Lessons Learned: Adding docetaxel to the modified FOLFOX7 backbone (DOF) is a feasible three-drug combination therapy for advanced gastric cancer with high activity, providing evidence that leucovorin is not necessary in this setting. The DOF regimen represents an alternative to the FLOT (5-FU 2,600 mg/m2 as 24-hour infusion with leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2) regimen that can be considered in select patients with advanced gastric cancer and is a potential choice in the curative setting. Background: The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity. Given the efficacy of platinum-taxane-fluoropyrimidine regimens, this phase II study evaluated the efficacy and toxicity of docetaxel, oxaliplatin, and 5-FU (DOF) for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: Patients with metastatic or unresectable gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease received docetaxel 50 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, and 5-FU 2,400 mg/m2 continuous intravenous infusion over 46 hours; cycles were repeated every 2 weeks. The primary endpoint was overall response rate (ORR). Results: Forty-four patients were enrolled. Assessment of treatment response and toxicity was feasible in 41 and 43 patients, respectively. ORR was 73.2{\%} (68.3{\%} partial response; 4.9{\%} complete response). Therapy was discontinued for progressive disease in 53{\%}, toxicity in 26{\%}, and death on treatment in 16{\%}. Two patients underwent surgical resection. Thirty-three patients (76.7{\%}) received at least seven cycles (7–34). Grade 3–4 toxicities occurred in 31 patients (72.1{\%}), including neutropenia (23.3{\%}), neurologic (20.9{\%}), and diarrhea (14.0{\%}). Median overall survival was 10.3 months. Conclusion: DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an option for select patients with unresectable or metastatic gastric or GEJ adenocarcinoma.",
author = "Rosenberg, {Ari Joseph} and Rademaker, {Alfred W} and Hochster, {Howard S.} and Theresa Ryan and Thomas Hensing and Veena Shankaran and Lisa Baddi and Devalingam Mahalingam and Mulcahy, {Mary Frances} and Benson, {Al B.}",
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Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma : A Phase II Study with Long-Term Follow-Up. / Rosenberg, Ari Joseph; Rademaker, Alfred W; Hochster, Howard S.; Ryan, Theresa; Hensing, Thomas; Shankaran, Veena; Baddi, Lisa; Mahalingam, Devalingam; Mulcahy, Mary Frances; Benson, Al B.

In: Oncologist, Vol. 24, No. 8, 01.01.2019, p. 1039-e642.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma

T2 - A Phase II Study with Long-Term Follow-Up

AU - Rosenberg, Ari Joseph

AU - Rademaker, Alfred W

AU - Hochster, Howard S.

AU - Ryan, Theresa

AU - Hensing, Thomas

AU - Shankaran, Veena

AU - Baddi, Lisa

AU - Mahalingam, Devalingam

AU - Mulcahy, Mary Frances

AU - Benson, Al B.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Lessons Learned: Adding docetaxel to the modified FOLFOX7 backbone (DOF) is a feasible three-drug combination therapy for advanced gastric cancer with high activity, providing evidence that leucovorin is not necessary in this setting. The DOF regimen represents an alternative to the FLOT (5-FU 2,600 mg/m2 as 24-hour infusion with leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2) regimen that can be considered in select patients with advanced gastric cancer and is a potential choice in the curative setting. Background: The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity. Given the efficacy of platinum-taxane-fluoropyrimidine regimens, this phase II study evaluated the efficacy and toxicity of docetaxel, oxaliplatin, and 5-FU (DOF) for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: Patients with metastatic or unresectable gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease received docetaxel 50 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, and 5-FU 2,400 mg/m2 continuous intravenous infusion over 46 hours; cycles were repeated every 2 weeks. The primary endpoint was overall response rate (ORR). Results: Forty-four patients were enrolled. Assessment of treatment response and toxicity was feasible in 41 and 43 patients, respectively. ORR was 73.2% (68.3% partial response; 4.9% complete response). Therapy was discontinued for progressive disease in 53%, toxicity in 26%, and death on treatment in 16%. Two patients underwent surgical resection. Thirty-three patients (76.7%) received at least seven cycles (7–34). Grade 3–4 toxicities occurred in 31 patients (72.1%), including neutropenia (23.3%), neurologic (20.9%), and diarrhea (14.0%). Median overall survival was 10.3 months. Conclusion: DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an option for select patients with unresectable or metastatic gastric or GEJ adenocarcinoma.

AB - Lessons Learned: Adding docetaxel to the modified FOLFOX7 backbone (DOF) is a feasible three-drug combination therapy for advanced gastric cancer with high activity, providing evidence that leucovorin is not necessary in this setting. The DOF regimen represents an alternative to the FLOT (5-FU 2,600 mg/m2 as 24-hour infusion with leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2) regimen that can be considered in select patients with advanced gastric cancer and is a potential choice in the curative setting. Background: The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity. Given the efficacy of platinum-taxane-fluoropyrimidine regimens, this phase II study evaluated the efficacy and toxicity of docetaxel, oxaliplatin, and 5-FU (DOF) for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: Patients with metastatic or unresectable gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease received docetaxel 50 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, and 5-FU 2,400 mg/m2 continuous intravenous infusion over 46 hours; cycles were repeated every 2 weeks. The primary endpoint was overall response rate (ORR). Results: Forty-four patients were enrolled. Assessment of treatment response and toxicity was feasible in 41 and 43 patients, respectively. ORR was 73.2% (68.3% partial response; 4.9% complete response). Therapy was discontinued for progressive disease in 53%, toxicity in 26%, and death on treatment in 16%. Two patients underwent surgical resection. Thirty-three patients (76.7%) received at least seven cycles (7–34). Grade 3–4 toxicities occurred in 31 patients (72.1%), including neutropenia (23.3%), neurologic (20.9%), and diarrhea (14.0%). Median overall survival was 10.3 months. Conclusion: DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an option for select patients with unresectable or metastatic gastric or GEJ adenocarcinoma.

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