First Line Treatment for Advanced Gastroesophageal Cancer: Capecitabine Plus Oxaliplatin (CAPOX) versus Epirubicin, Oxaliplatin Plus Capecitabine (EOX)

Research Article

Austin J Cancer Clin Res. 2017; 4(1): 1073.

First Line Treatment for Advanced Gastroesophageal Cancer: Capecitabine Plus Oxaliplatin (CAPOX) versus Epirubicin, Oxaliplatin Plus Capecitabine (EOX)

Pani CK¹, Dubashi B¹, Cyriac SL¹, Dhanraj KM¹, Verma SK², Sistla SC³ and Kayal S¹*

¹Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), India

²Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), India

³Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), India

*Corresponding author: Kayal S, Department of Medical Oncology, Regional Cancer Centre, JIPMER, Dhanvantari Nagar, Puducherry-605006, India

Received: January 27, 2017; Accepted: February 27, 2017; Published: March 01, 2017


Chemotherapy is the mainstay of treatment for advanced gastroesophageal cancer (AGC). There is no consensus whether doublet or triplet chemotherapy is better. Hence our study aimed to compare CAPOX (capecitabine and oxaliplatin) with EOX (epirubicin, oxaliplatin plus capecitabine) as first line treatment for AGC. From December 2012 to July 2014, total of 69 patients were randomly assigned; 35 to EOX arm (epirubicin 50 mg/m2 on day1, capecitabine 625 mg/m2 twice daily for 21 day and oxaliplatin 130 mg/m2 on day1 three weekly for 8 cycle) and 34 to CAPOX arm (capecitabine 1000 mg/m2 twice daily for 14 days and oxaliplatin 130 mg/m2 on day 1 in a three weekly cycle for 8 cycle). Median age at diagnosis was 55 years. The median number of chemotherapy cycle delivered was 7.45% completed planned treatment. 63.8% patient needed dose modification and 33.3% had treatment discontinuation due to grade 3/4 toxicity. Incidence of grade 3/4 neutropenia was significantly more in EOX where as diarrhoea and vomiting were more in CAPOX group. The ORR (overall response rate) was 63% in the entire cohort and 54.5% and 71.4% in the CAPOX and EOX group respectively. Median follow up was 15.2 month. Median OS (overall survival) was 8.1 and 10.3 months in the CAPOX and EOX groups respectively; p=0.298, however there was a trend favouring PFS (progression free survival) in the EOX group (5.5 vs. 8.3 months in CAPOX and EOX respectively; p=0.06). No significant difference was observed between the two regimens with respect to ORR, PFS and OS. Doublet chemotherapy regimen (CAPOX) has similar efficacy as a triplet regimen (EOX), however, with higher incidence of gastrointestinal toxicity.

Keywords: Advanced gastric cancer; Palliative chemotherapy; Epirubicin; Oxaliplatin; Capecitabine


AGC: Advanced Gastroesophageal Cancer; ALT: Alanine Transaminase; ALP: Alkaline Phosphatise; AST: Aspartate Transaminase; CAPOX: Capecitabine and Oxaliplatin; CR: Complete Response; EOX: Epirubicin, Oxaliplatin Plus Capecitabine; ECOG: Eastern Co-Operative Group; GEJ: Gastro Esophageal Junction; HR: Hazard Ratio; NCI-CTCAE: National Cancer Institute - Common Terminology Criteria for Adverse Events; ORR: Overall Response Rate; OS: Overall Survival; PD: Progressive Disease; PFS: Progression Free Survival; PR: Partial Response; RECIST: Response Evaluation Criteria in Solid Tumors; SD: Stable Disease; TTP: Time To Progression; ULN: Upper Limit of Normal


Gastric cancer is the fifth most common cancer and third most common cause of death worldwide. Despite recent advances in the diagnosis and treatment of gastric cancer, many patients present with advanced disease and have poor survival [1]. According to data from the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program, the five-year survival for patients with gastric cancer improved only modestly over the last 50 years, from 12 percent in the years 1950 to 1954, 22 percent during the period 1996 to 2003 [2]. The median survival for advanced gastric cancer is about four months without treatment, and this extends up to one year with current treatment modalities. Chemotherapy is the mainstay of treatment for advanced gastroesophageal cancer (AGC). Initial trials used single agent drugs versus best supportive care. Subsequent studies showed that combination chemotherapy result in superior outcomes compared to monotherapy [3]. Triple drug regimen is better than double in the form of increased overall response rate (ORR) and time to progression (TTP) but is associated with increased myelosuppression and infectious complications [4]. The recent REAL-2 trial has proven that capecitabine is equivalent to 5-FU and oxaliplatin is equivalent to cisplatin with comparable or even more response rate and survival [5]. Combination therapies using cisplatin and fluoropyrimidines with or without epirubicin or docetaxel have been widely used as first-line treatments for AGC. There is no strong data whether doublet or triplet chemotherapy is better, though ORR and TTP favors triplet regimen, there is increased toxicity. We conducted a pilot study at our centre of capecitabine and oxaliplatin (CAPOX) in locally advanced and metastatic gastroesophageal cancer (unpublished data) that showed an ORR of 47.3%, and median survival of 8 months, which are at par with current literature. With this encouraging data we planned to conduct a randomized clinical study comparing CAPOX with epirubicin, capecitabine and oxaliplatin (EOX) in AGC.


It was a single centre randomized prospective clinical study conducted in the department of Medical Oncology, Regional Cancer Centre, JIPMER, Puducherry. Patients were randomized by computer generated simple randomization method. The main inclusion criteria were histologically proven adenocarcinoma or squamous cell carcinoma of gastric or gastroesophageal region, locally advanced and metastatic disease, age 18-70 years, Eastern cooperative group (ECOG) performance status less than equal to 2 after initial stabilization, able to take oral medication, Chemotherapy naïve patients and a valid informed consent. The exclusion criteria were prior radiotherapy/ chemotherapy, significant organ dysfunction (Ejection fraction <50%, serum Creatinine >2 mg/dl, alanine transaminase (ALT) and aspartate transaminase (AST) ≥3 times upper limit of nominal (ULN), alkaline phosphatase (ALP) ≥5 times ULN, serum bilirubin >3 mg/dl) and concomitant malignancy. The study was started after approval by the Institute Ethics Committee.

Patient characteristics

A total of 69 patients were enrolled during the study period from February 2013 to July 2014 and data was analyzed in December 2014. Patients were randomly assigned to CAPOX arm (group A, n=34) and to EOX arm (group B, n=35). Multiple sites of metastasis and ascites were seen in one-third of cases. Palliative surgical intervention in the form of gastric bypass surgery, feeding jejunostomy was done in 58% of our patients. The baseline patient and disease characteristics (Table 1) were similar in both groups except mean weight at presentation (44.4±10.45 vs. 50±10.84, p=0.033) and mean hemoglobin at presentation (9.6±1.63 vs. 10.7±2.09, p=0.018), which were significantly high in the EOX arm.