Efficacy and safety of SOX chemotherapy with or without surgery in AFP-producing advanced gastric cancer

Abstract

The present study investigated the clinical efficacy of S-1 plus oxaliplatin (SOX) regimen, with or without surgery in α-fetoprotein-producing gastric cancer (APGC) with liver metastasis. A total of 24 patients with APGC treated at the Liaocheng People's Hospital between January 2011 and December 2013 were retrospectively reviewed. Clinical efficacy and patient safety were compared between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the SOX group were 6.5 [95% confidence interval (CI), 4.6-8.4] and 13.5 (95% CI, 8.1-18.9) months, respectively. The corresponding indicators in the SOX and surgery group were 7.0 (95% CI, 5.7-8.3) and 14 (95% CI, 11.0-17.1) months, respectively. There was no significant difference in PFS and OS between the two groups (P=0.703 and 0.710, respectively). The adverse effects of leucopenia, neutropenia, anemia and diarrhea occurred in ~10% of patients in the SOX group and in 14.3% (2/14), 7.14% (1/14), 14.3% (2/14) and 7.14% (1/14), respectively, in the surgery group. No significant difference was identified between groups in terms of overall incidence of adverse effects (P=0.17). However, severe adverse events, including gastroplegia, pancreatic fistula, pulmonary infection and refractory ascites, occurred only in the SOX plus surgery group [incidence rate for severe adverse events, 7.14% (1/14); P<0.001 between groups]. In conclusion, SOX chemotherapy is safe and effective in patients with APGC and liver metastasis. However, the addition of surgery to SOX chemotherapy may not improve the disease control rate and may increase the adverse effects.

Keywords: S-1 plus oxaliplatin regimen; liver metastasis; surgery; α-fetoprotein-producing gastric cancer.

Figure 1.

Histopathological examination of hematoxylin and eosin-stained α-fetoprotein-producing gastric cancer tissues demonstrating poorly differentiated cells, diffuse growth pattern, no cell junctions, fewer glands and signet ring cells. (A) Diffusely distributed cells (magnification, ×10); (B) irregular gland morphology (magnification, ×100); (C) signet ring cells (magnification, ×100; arrows); (D) irregular gland morphology (magnification, ×200).

Figure 2.

IHC staining of tissues of α-fetoprotein-producing gastric cancer demonstrating positive parenchymal cancer cells (pale brown), mesenchymal (negative) cells, signet ring cells and glands (indicated by arrows). (A) Magnification, ×10. (B) Magnification, ×100. (C) IHC staining identifying partial cancer cell positive staining for carcinoembryonic antigen (brown). (D) IHC staining for cancer antigen 19–9 identifying cancer cells with positive staining and mesenchymal cells negative for cancer antigen 19–9 (magnification, ×10). IHC, immunohistochemistry.

Figure 3.

Images of APGC lesions captured from gastroscopy. (A) Patient with erosive gastritis. (B) APGC with a small focus (lesion diameter, 1 cm). (C) APGC with medium focus (diameter, <6 cm). (D) APGC with a large focus (diameter, >6 cm). Arrows indicate (A) gastritis and (B-D) APGC lesions. APGC, α-fetoprotein-producing gastric cancer.

Figure 4.

CT radiographs of α-fetoprotein-producing gastric cancer patient (SOX plus surgery group) with extragastric lymphatic metastasis treated with radical gastrectomy (distal subtotal gastrectomy and D2 lymph node dissection) and post-operative SOX regimen for 6 cycles. (A) Extragastric metastatic lymph nodes. (B) CT scan 2 months after surgery. (C) CT scan a year following surgery. (D) CT scan 2 years after surgery demonstrating no signs of recurrence. (A) Arrows indicate extragastric metastatic lymph nodes. (B-D) Titanium nail sutures in the stump of stomach are indicated by arrows. SOX, S-1 and oxaliplatin chemotherapy regime; CT, computed tomography.

Figure 5.

Computed tomography radiograph of a patient with α-fetoprotein-producing gastric cancer treated with SOX plus subtotal gastrectomy. (A) Multiple hepatic metastatic lesions at enrollment. (B) Attenuated metastatic lesions with smaller margin of tumor invasion following a month of SOX. (C) Reduced metastases following 3 months of chemotherapy. (D) Flared-up metastatic lesions caused by interruption in chemotherapy due to recurrent fever in the 2 months following surgery. (E) Attenuated metastatic lesions following SOX chemotherapy started 4 months after surgery. (F) Recurrence of metastatic lesions 1 year after surgery due to interruption in chemotherapy necessitated by the poor general condition of the patient. The patient developed multiple metastases 1 year after surgery and succumbed to multiple organ failure 6 months later. SOX, S-1 and oxaliplatin chemotherapy. Arrows indicate extragastric metastatic lymph nodes.

Figure 6.

Computed tomography radiographs of a patient with α-fetoprotein-producing gastric cancer treated with SOX. (A) A metastatic lesion in liver at enrollment. (B) Significantly attenuated metastatic lesion in the liver following 1 month of SOX treatment. (C) No sign of metastasis following two months of SOX treatment. (D) No recurrence of metastasis following 2 years of regular SOX regimen and without surgical resection of primary lesion. SOX, S-1 and oxaliplatin chemotherapy. Arrows indicate intrahepatic metastatic lesions.

Figure 7.

Temporal representation of AFP levels in AFP-producing gastric cancer. (A) Typical trend of AFP levels of a patient in the SOX group. (B) Typical trend of AFP levels of a patient in the SOX group. (C) Typical trend of AFP levels of a patient in the SOX plus surgery group. (D) Typical trend of AFP levels of a patient in the SOX plus surgery group. Black lines indicate starting points for treatment. AFP, α-fetoprotein; SOX, combination chemotherapy with S-1 and oxaliplatin; deceased, succumbed to disease; loss, loss to follow-up.

Figure 8.

Kaplan-Meier estimator survival curves. (A) Progression-free survival rate in the two study groups. (B) Overall survival rate in the two groups. Chemotherapy group, SOX treatment alone; Surgery group, SOX treatment plus surgery (resection of primary lesion). SOX, S-1 and oxaliplatin chemotherapy.