The quality of life in neoadjuvant versus adjuvant therapy of esophageal cancer treatment trial (QUINTETT): Randomized parallel clinical superiority trial

Richard A Malthaner; Edward Yu; Michael Sanatani; Debra Lewis; Andrew Warner; A Rashid Dar; Brian P Yaremko; Joel Bierer; David A Palma; Dalilah Fortin; Richard I Inculet; Eric Fréchette; Jacques Raphael; Stewart Gaede; Sara Kuruvilla; Jawaid Younus; Mark D Vincent; George B Rodrigues

doi:10.1111/1759-7714.14433

The quality of life in neoadjuvant versus adjuvant therapy of esophageal cancer treatment trial (QUINTETT): Randomized parallel clinical superiority trial

Thorac Cancer. 2022 Jul;13(13):1898-1915. doi: 10.1111/1759-7714.14433. Epub 2022 May 24.

Authors

Richard A Malthaner¹, Edward Yu², Michael Sanatani³, Debra Lewis¹, Andrew Warner², A Rashid Dar², Brian P Yaremko², Joel Bierer¹, David A Palma², Dalilah Fortin¹, Richard I Inculet¹, Eric Fréchette¹, Jacques Raphael³, Stewart Gaede², Sara Kuruvilla³, Jawaid Younus³, Mark D Vincent³, George B Rodrigues²

Affiliations

¹ Department of Oncology, Divisions of Thoracic Surgery and Surgical Oncology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
² Radiation Oncology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
³ Medical Oncology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Abstract

Background: We compared the health-related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I-III esophageal cancer.

Methods: A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5-fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5-fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection.

Results: There was no significant difference in the functional assessment of cancer therapy-esophageal (FACT-E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre-treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT-E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-OG25), and EuroQol 5-D-3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30-day mortalities and 2% vs. 10% 90-day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5-year: 35% vs. 32%, p = 0.409) or disease-free survival (DFS) (5-year: 31% vs. 30%, p = 0.710).

Conclusion: Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed.

Trial registration: ClinicalTrials.gov NCT00907543.

Keywords: adjuvant; esophageal cancer; neoadjuvant; quality of life; randomized; trimodality.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Chemotherapy, Adjuvant / methods
Cisplatin / therapeutic use
Esophageal Neoplasms* / drug therapy
Esophageal Neoplasms* / surgery
Fluorouracil / therapeutic use
Humans
Neoadjuvant Therapy* / methods
Quality of Life
Treatment Outcome

Substances

Cisplatin
Fluorouracil

Associated data

ClinicalTrials.gov/NCT00907543