Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial

Keun-Wook Lee; Dae Young Zang; Min-Hee Ryu; Ki Hyang Kim; Mi-Jung Kim; Hye Sook Han; Sung Ae Koh; Jin Hyun Park; Jin Won Kim; Byung-Ho Nam; In Sil Choi

doi:10.1016/j.conctc.2017.08.006

Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial

Contemp Clin Trials Commun. 2017 Aug 18:8:55-61. doi: 10.1016/j.conctc.2017.08.006. eCollection 2017 Dec.

Authors

Keun-Wook Lee¹, Dae Young Zang², Min-Hee Ryu³, Ki Hyang Kim⁴, Mi-Jung Kim⁵, Hye Sook Han⁶, Sung Ae Koh⁷, Jin Hyun Park⁸, Jin Won Kim¹, Byung-Ho Nam⁹, In Sil Choi⁸

Affiliations

¹ Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
² Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea.
³ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁴ Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, South Korea.
⁵ Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.
⁶ Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, South Korea.
⁷ Department of Internal Medicine, Yeungnam University Medical Center, Daegu, South Korea.
⁸ Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea.
⁹ Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, South Korea.

Abstract

Introduction: The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy.

Methods: This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety.

Discussion: We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

Keywords: 5-FU, 5-fluorouracil; ADL, activities of daily living; AGC, advanced gastric cancer; AST/ALT, aspartate aminotransferase/alanine aminotransferase; CCr, creatinine clearance; CGA, comprehensive geriatric assessment; CI, confidence interval; CRF, case report form; CT, computed tomography; Chemotherapy; DSMB, data safety monitoring board; ECOG, Eastern Cooperative Oncology Group; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer core quality of life questionnaire; EORTC QLQ-STO22, European Organization for Research and Treatment of Cancer quality of life questionnaire-gastric; Elderly; FAS, full analysis set; Gastric cancer; HER-2, human epidermal growth factor receptor-2; HR, hazard ratio; IADL, independent activities of daily living; IIT, intent to treat; KCSG, Korean Cancer Study Group; KG-7, Korean Cancer Study Group geriatric tool; KPS, Karnofsky performance status; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; OS, overall survival; PFS, progression-free survival; PPS, per-protocol set; PS, performance status; QoL, quality of life; RCT, randomized controlled trial; RECIST, Response Evaluation Criteria in Solid Tumors; RR, response rate; Randomized controlled trial; SAE, serious adverse event; SEER, Surveillance, Epidemiology, and End Results; UNL, upper normal limit.