Neoadjuvant Docetaxel, Oxaliplatin, and S-1 in Resectable Advanced Gastric Cancer

Abstract

Kang et al 1 have reported on the results of the PRODIGY trial in Journal of Clinical Oncology. The results showed that neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 (CSC) resulted in improved progression-free survival (PFS) versus D2 surgery followed by adjuvant S-1 (SC; hazard ratio, 0.70; 95% CI, 0.52 to 0.95; P 5 .023) in resectable locally advanced gastric cancer (LAGC), and the authors suggest that neoadjuvant DOS to D2 gastrectomy and adjuvant S-1 should be considered a standard treatment for patients in Asia with LAGC. Despite the encouraging results, some aspects still warrant closer attention.

Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy

“…By enhancing tubulin polymerization and inhibiting microtubule depolymerization, docetaxel leads to the formation of stable nonfunctional microtubule bundles and destroys the process of mitosis in tumor cells. 114 Docetaxel is one of the first-line chemotherapeutic drugs for the treatment of recurrent or metastatic cervical cancer. However, it leads to the enrichment of CSCs and the decreased expression of E-cadherin associated with EMT, resulting in treatment failure.…”

Reply to D.-C. Mo et al

“…We thank Dr Mo et al 1 for their comments on our recently published article reporting the results of the PRODIGY study. 2…”

“…First, Mo et al 1 question the definition of progressive disease (PD) used in PRODIGY. Defining PD in neoadjuvant studies of gastric cancer is challenging as there is no established consensus or agreed definition of progression-free survival (PFS) in this setting.…”

“…As discussed in our manuscript, the efficacy of neoadjuvant chemotherapy results, at least in part, from improved complete resection rates. As Mo et al 1 stated, PFS was defined in other studies 5-7 as the time from random assignment to local recurrence or progression, distant recurrence, or death from any cause. Incomplete resection was, however, included among the events defining disease-free survival (DFS) in the FNCLCC and FFCD trial, 8 although this is not clearly stated in the MAGIC 6 or FLOT4 manuscripts.…”

“…Mo et al 1 also argue that OS should have been the primary end point in PRODIGY. Although OS is a definitive end point in oncology studies, it is true that surrogacy of PFS or DFS for OS is not fully established in the context of neoadjuvant chemotherapy, although this is accepted in adjuvant studies.…”