Low pretherapy skeletal muscle mass index is associated with an increased risk of febrile neutropenia in patients with esophageal cancer receiving docetaxel + cisplatin + 5-fluorouracil (DCF) therapy.

PURPOSE: Docetaxel + cisplatin + 5-fluorouracil (DCF) therapy, a frequently prescribed regimen for esophageal cancer, is associated with a high risk of febrile neutropenia (FN). This study investigated whether a low skeletal muscle mass index (SMI) is an independent risk factor for FN. METHODS: This retrospective, observational study investigated the SMI of patients with esophageal cancer who received DCF therapy between March 2018 and July 2020. Based on the Asian sarcopenia criteria, patients were divided into two groups: high and low SMI (SMI of < 7.0 and 5.7 kg/m2 for males and females, respectively). The incidence of FN was then compared between the two groups. RESULTS: Thirty-nine patients (20 and 19 in the high- and low-SMI groups, respectively) were included in this study. The incidence of FN was significantly higher in the low-SMI group (63.2% vs. 20.0%, P = 0.006). Univariable and multivariable logistic regression analyses revealed that a low SMI was an independent risk factor for FN (odds ratio, 7.178; 95% confidence interval, 1.272-40.507; P = 0.026). In addition, the frequency of dose reduction in DCF therapy was significantly higher in the low-SMI group (68.4% vs. 35.0%, P = 0.037). CONCLUSION: Low SMI is an independent risk factor for FN in patients with esophageal cancer receiving DCF therapy.

Long-term outcomes and safety of radical transmediastinal esophagectomy with preoperative docetaxel, cisplatin, and 5-fluorouracil combination chemotherapy for locally advanced squamous cell carcinoma of the thoracic esophagus.

BACKGROUND: It is unknown whether transmediastinal esophagectomy (TME) is an acceptable surgical procedure for locally advanced esophageal squamous cell carcinoma (ESCC). Therefore, we investigated the feasibility of long-term survival after TME with neoadjuvant docetaxel, cisplatin, and 5-fluorouracil combination chemotherapy (DCF therapy). METHODS: This retrospective, observational study included locally advanced resectable ESCC. All patients received two cycles of preoperative DCF therapy (60 mg/m2 of docetaxel and cisplatin on day 1 and 700 mg/m2/day of 5-FU on days 1-5 in each cycle) followed by radical TME. The main outcomes were survival and the rate of adverse events of chemotherapy and surgery. RESULTS: Sixteen patients were included in this study. All patients received two cycles of DCF therapy, followed by surgery. The median follow-up duration of the 16 patients was 35.4 months. The 2-year overall survival (OS) was 93.3% (95% confidence interval [CI], 61.3-99.0), and the 3-year OS was 78.8% (95% CI, 47.3-92.7). The 2-year and 3-year relapse-free survivals were both 73.3% (95% CI, 43.6-89.1). Leukopenia and neutropenia occurred in most patients; however, they were controllable. Fifteen patients completed TME, and one was converted to open transthoracic esophagectomy because of tracheal injury. Three-field dissection was performed for 12 of 16 patients (75%), and R0 resection was achieved in 15 of 16 patients (93.8%). Three cases of grade IIIb chylothorax were observed. There was no mortality in this study. CONCLUSION: Combined neoadjuvant DCF and TME for locally advanced ESCC was safe and less invasive than traditional therapies and had a satisfactory long-term prognosis.

Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807).

We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m(2) [dose level (DL)1] or 40 mg/m(2) [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m(2) cisplatin, day 1; 800 mg/m(2) fluorouracil, days 1-5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P < 0.0001; 95% confidence interval, 48-75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737.

Intraperitoneal perforation through lymph node metastases in a patient with esophageal squamous cell carcinoma during intensive chemotherapy: A case report with literature review.

INTRODUCTION: Esophageal fistula after treatment is a critical and fatal complication of esophageal cancer. A fistula forming from lower thoracic esophageal cancer to the peritoneum through lymph node metastases following chemotherapy has not been reported. We report a case of peritonitis due to lymph node perforation through the tumor ulcer after induction of biweekly docetaxel, cisplatin, and 5FU combined chemotherapy (Bi-DCF) for advanced esophageal squamous cell carcinoma (ESCC). PRESENTATION OF CASE: A 48-year-old woman was referred to us with a diagnosis of lower thoracic ESCC and thoracoabdominal aortic aneurysm. Esophagogastroduodenoscopy showed a circumferential type 3 tumor with stenosis in the lower thoracic esophagus. Contrast-enhanced computed tomography (CT) showed a thoracoabdominal aortic aneurysm and wall thickening of the lower thoracic esophagus that was suspicious of esophageal cancer. Lymph node metastases dumpling from around the tumor to abdominal cavity were also observed. The initial diagnosis was ESCC T3 N3 M1 (para-aortic lymph nodes and liver) Stage IVB. She was started on Bi-DCF (docetaxel 35 mg/m2 days 1/15, cisplatin 40 mg/m2 days 1/15, 5FU 400 mg/m2 days 1-5, 15-19) as the first-line regimen. The third day after starting chemotherapy, she felt strong abdominal pain, and internal necrosis of lymph nodes around the primary lesion and free air in the abdominal cavity were found. Peritonitis was diagnosed due to a fistula formed from the lower thoracic ESCC to the peritoneum through lymph node metastases. She underwent emergency laparoscopic drainage, omental filling, and jejunostomy. Postoperatively, her general condition and inflammatory findings improved within 10 days, and she could continue intensive chemotherapy as scheduled. DISCUSSION: Because of the risk of perforation and fistula in regimens that are expected to cause tumor shrinkage, careful observation may be required after starting chemotherapy. CONCLUSION: We report the first case of peritonitis caused by perforation through lymph node metastasis of thoracic esophageal cancer.

Downstaging and Histological Effects Might Be Reliable Predictors of the Efficacy of DOC+CDDP+5-FU (DCF) as Neoadjuvant Therapy for Stage III or Borderline Resectable Esophageal Cancer: a Single Institute Experience.

PURPOSE: In Japan, two courses of CDDP+5-FU (CF) therapy followed by surgery are accepted as a standard treatment for stage II/III esophageal cancer (EC) based on the results of the JCOG9907 trial. To gain a better survival, benefit especially for stage III patients in comparison with CF therapy, a three-arm phase III trial (neoadjuvant setting: CF vs. CF + radiation vs. DOC+CF [DCF]) is ongoing. We have aggressively performed DCF therapy for stage III or IV patients since October 2014. We herein review the outcomes of DCF therapy. METHODS: We retrospectively reviewed the cases of 27 patients with stage III or IV EC (male, n = 24; female, n = 3; median age, 70.0 years) who received DCF therapy. RESULTS: The response rate was 48.1%. Downstaging was achieved over the course of treatment in 14 patients (51.9%). Twenty-six patients transitioned to surgery, with 25 receiving R0 resection. DCF-treated patients who achieved downstaging showed significantly longer relapse-free survival (RFS) than those without downstaging (p = 0.0002). DCF-treated patients with a grade ≥ 1b histological effect showed significantly longer RFS than those with a grade < 1b effect (p = 0.0282). The multivariate analysis showed that downstaging was the only factor significantly associated with RFS in DCF-treated patients. CONCLUSIONS: DCF therapy for stage ≥ III esophageal carcinoma is both feasible and effective. These findings suggest that downstaging and the histological effect might predict the effects of DCF therapy for EC.

Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil.

BACKGROUND/AIM: The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF). PATIENTS AND METHODS: The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed. RESULTS: Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUVmax) after induction DCF therapy and small decreases in SUVmax from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis. CONCLUSION: Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUVmax DCF therapy are associated with early disease relapse and death.

Successfully treated advanced esophageal cancer with left axillary lymph node metastasis and synchronous right breast cancer: a case report.

The incidence of double cancer of the esophagus and breast is rare, and axillary lymph node metastasis (ALM) in esophageal cancer is also very rare. We report a case of advanced esophageal cancer with left ALM and synchronous right breast cancer. A 64-year-old woman was admitted to our hospital with dysphagia. The clinical diagnosis was esophageal cancer (T3N0M1 stage IV) and right breast cancer (T1cN0M0 stage I). She was initially treated with triple chemotherapy with docetaxel, cisplatin, and 5-fluorouracil. The primary lesion in the esophagus achieved almost complete response as assessed by esophageal endoscopy. A computed tomography scan showed that the left ALM reduced in size and that stable disease was achieved for the right breast cancer. She underwent partial mastectomy of the right breast and bilateral axillary lymph node dissection. The histopathological diagnosis of the breast cancer was T1cN1M0 stage IIA. The lymph nodes from the left axilla contained metastatic cells from the squamous cell carcinoma of the esophagus. Complete response was achieved for the primary lesion in the esophagus following chemoradiotherapy (CRT), and the patient has been relapse free 2 years after treatment. Thus, we report the successful treatment of synchronous double cancers of the esophagus with left ALM and right breast by combination therapy with chemotherapy, CRT, and surgery.