Phase II Trial of 5-Fluorouracil, Docetaxel, and Nedaplatin (UDON) Combination Therapy for Recurrent or Metastatic Esophageal Cancer

Abstract

Lessons Learned. The 5‐fluorouracil, docetaxel, and nedaplatin (UDON) regimen was well tolerated and showed promising antitumor activity in terms of both objective response rate and survival for patients with advanced or recurrent esophageal squamous cell carcinoma in the first‐line setting. UDON may be an optimal treatment option for patients with advanced esophageal cancer who are unfit for docetaxel, cisplatin, and 5‐fluorouracil regimens. The high response rate as well as the rapid and marked tumor shrinkage associated with UDON suggest that further evaluation of this regimen in the neoadjuvant setting is warranted. Background. A phase II study was performed to evaluate the efficacy and safety of 5‐fluorouracil (5‐FU), docetaxel, and nedaplatin (UDON) combination therapy for untreated recurrent or metastatic esophageal cancer. Methods. Patients received intravenous nedaplatin (90 mg/m 2 ) on day 1, docetaxel (35 mg/m 2 ) on days 1 and 15, and 5‐fluorouracil (800 mg/m 2 ) on days 1–5 of a 4‐week cycle. The primary endpoint was response rate, with secondary endpoints including overall survival (OS), progression‐free survival (PFS), dysphagia score, and adverse events. Results. Between March 2015 and July 2017, 23 patients were enrolled. Of 22 evaluable patients, 16 and 4 individuals experienced a partial response and stable disease, respectively, yielding a response rate of 72.7% (95% confidence interval [CI], 49.8%–89.3%) and disease control rate of 90.9% (95% CI, 70.8%–98.9%). Median OS and PFS were 11.2 months (95% CI, 9.1 months to not reached) and 6.0 months (95% CI, 2.5–10.6 months), respectively. Eleven (64.7%) of the 17 patients with a primary lesion showed amelioration of dysphagia after treatment. Frequent adverse events of grade 3 or 4 included neutropenia (87.0%) and leukopenia (39.1%). Febrile neutropenia was observed in two patients (8.7%). Conclusion. This phase II study demonstrated promising antitumor activity and good tolerability of UDON.

Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first‐line treatment of advanced esophageal squamous cell carcinoma

“…Currently, 5-fluorouracil and platinum are the therapeutic combination recommended in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines [4] and the Pan-Asian adapted European Society of Medical Oncology (ESMO) Clinical Practice Guidelines [5] as the first-line treatment for patients with metastatic ESCC, while newer agents including paclitaxel, docetaxel, and irinotecan are also acceptable options although lack of solid evidence from phase III clinical trials. The response rates ranged between 35%-56.5% with doublet chemotherapy [6][7][8][9][10][11] and 43.9%-72.7% with triplet regimens [12][13][14]. The survival outcomes of patients treated with these combinations have been unsatisfactory, as the median progression-free survival (PFS) ranged between 4.5 and 7 months, and the median overall survival (OS) was typically around 1 year [6][7][8][9][10][11][12][13][14][15].…”

“…The response rates ranged between 35%-56.5% with doublet chemotherapy [6][7][8][9][10][11] and 43.9%-72.7% with triplet regimens [12][13][14]. The survival outcomes of patients treated with these combinations have been unsatisfactory, as the median progression-free survival (PFS) ranged between 4.5 and 7 months, and the median overall survival (OS) was typically around 1 year [6][7][8][9][10][11][12][13][14][15]. Hence, there is an unmet need for novel anti-tumor agents to treat patients with advanced ESCC.…”

Recent Progress in the Neoadjuvant Treatment Strategy for Locally Advanced Esophageal Cancer

“…The biweekly triple chemotherapy with docetaxel, 5-FU, and nedaplatin (UDON) has been proved to have good antitumor activity and tolerability. UDON has been evaluated as a first-line treatment for patients with advanced or recurrent SCC in Japan [40].…”

Nedaplatin-based chemotherapy or cisplatin-based chemotherapy combined with intensity-modulated radiotherapy achieve similar efficacy for stage II-IVa nasopharyngeal carcinoma patients

“…Nedaplatin is a second-generation derivative of platinum agents that has a similar anticancer potency and less digestive and renal toxicities than cisplatin 9 . Nedaplatin has been widely used in the treatment of non-small-cell lung cancer 10 , oesophageal carcinoma 11 , and head and neck carcinoma 12 . In the field of NPC treatment, several phase II trials have demonstrated that nedaplatin-based chemotherapy is effective as a second-line and first-line treatment for recurrent and metastatic NPC 13 – 15 .…”