Docetaxel/cisplatin/5-fluorouracil Research Articles

Prognostic Impact of Thoracic Duct Resection in Patients Who Underwent Transthoracic Esophagectomy Following Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma: Exploratory Analysis of JCOG1109.

Although several studies have investigated whether thoracic duct (TD) resection improves prognosis, the conclusion remains controversial. JCOG1109 is a three-arm randomized phase III trial to confirm the survival advantage of docetaxel, cisplatin, 5-fluorouracil (DCF), and cisplatin plus 5-fluorouracil (CF) combined with radiotherapy (CF-RT) over CF as neoadjuvant treatment. The study aimed to evaluate the survival impact of TD resection and its association with neoadjuvant treatment and pathological response in patients enrolled in JCOG1109. Clinicopathological factors, surgical results, and prognosis were compared between TD preserved and resected groups. The survival impact of TD resection was also evaluated in the subgroups on the basis of combinations of preoperative therapy and pathological response. Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200) in JCOG1109. Of them, 541 patients underwent esophagectomy (183/181/177), and TD was resected in 265 patients (93/91/81). For the entire cohort, TD resection was not a significant prognostic factor for overall survival in the multivariable analysis (HR 1.20, 95% CI 0.91-1.57). In the subgroup analyses by combinations of neoadjuvant treatment and pathological response, TD resected group had a significantly better overall survival compared with TD preserved group in patients who received DCF and achieved pathological response (HR 0.20, 95% CI 0.07-0.61). The survival benefit of TD resection was not demonstrated in patients with surgically resectable esophageal squamous cell carcinoma enrolled in JCOG1109. The residual tumor burden after neoadjuvant treatment might be linked to the survival impact of TD resection.

Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance.

The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxel + cisplatin + fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant ( P < 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group ( P < 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group ( P < 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.

Adjuvant Concurrent Chemoradiotherapy (CRT) plus Docetaxel-Cisplatin-Fluorouracil (DCF) versus CRT plus Fluorouracil-Folinic Acid (FUFA) in Stage III Gastric Cancer.

Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.

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

PurposeDocetaxel + 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.MethodsThis 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.ResultsThirty-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).ConclusionLow SMI is an independent risk factor for FN in patients with esophageal cancer receiving DCF therapy.

Neoadjuvant chemotherapy outcome with taxane-based versus non-taxane protocols in gastric cancer.

Gastric cancer is the fifth most common cancer worldwide. One of the chemotherapy agents, taxanes is important in increasing patients' survival. The purpose of this study is to assess the efficacy of taxane-based drugs versus non-taxanes in neoadjuvant chemotherapy in non-metastatic gastric adenocarcinoma (GA) in Iranian patients. In a historical cohort method, 65 patients between 18 and 75 years old who suffered from non-metastatic GA were included. Nineteen and 21 and 25 patients, had undergone DCF (docetaxel, cisplatin, 5fluorouracil) and FLOT (5fluorouracil, leucovorin, oxaliplatin, docetaxel) and FOLFOX6 (oxaliplatin, leucovorin, 5fluorouracil) regimens, respectively, between 2018 and 2021. Survival criteria consisting of progression-free survival (PFS), overall survival (OS), progression rate, and mortality rate were evaluated using the Kaplan-Meier method, in a three-year follow-up period. The majority of patients were male (72.3%), with a median age of 65 years. Most of the patients had lesions with tumor, node, metastasis (TNM) stage IIIb (27.7%) and poor differentiated pathological grade (49.2%). OS time had a significant correlation with the low TNM stage (P = 0.01), well-differentiated pathological grade (P = 0.005), and FLOT vs. FOLFOX protocol (20.3 vs. 12.2 months, respectively. P =0.04). FLOT regimen had significantly better OS survival vs. DCF regimen (20.3 vs. 15.4 months, respectively, P = 0.03). No significant correlation was observed between survival criteria and other factors like gender, age, past medical history, Karnofsky scale, and tumor location in the stomach. The taxane-based arm (sum of DSF and FLOT) had no superiority over the non-taxane arm in survival criteria. FLOT protocol, as a taxane-based regimen had better survival compared to FOLFOX protocol in neoadjuvant chemotherapy in gastric non-metastatic adenocarcinoma.

Efficacy and safety of FLOT regimen vs DCF, FOLFOX, and ECF regimens as perioperative chemotherapy treatments for resectable gastric cancer patients; a report from the middle east.

This study aimed to compare the efficacy and toxicity of perioperative chemotherapy regimens including epirubicin, cisplatin, 5-fluorouracil (ECF), docetaxel, cisplatin, 5-fluorouracil (DCF), leucovorin, 5-fluorouracil, oxaliplatin (FOLFOX), and 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) to identify the most effective chemotherapy regimen with less toxicity. This retrospective cohort study (2014-2021) was based on 152 eligible resectable gastric cancer patients who had received one of the perioperative mentioned chemotherapy regimens and followed for at least two years. The primary endpoint of this study was overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and R0 resection. Of included patients, 21%, 33.7%, 24.3%, and 21% had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 30-month follow-ups, OS was higher with the FLOT regimen in comparison with other regimens (hazard ratio = 0. 276). The median OS of the FLOT regimen was 39 months. Besides, the median OS was 28, 25, and 21 months for DCF, FOLOFX, and ECF regimens, respectively. Moreover, a median PFS of 24, 18, 17, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank < 0.001). FLOT regimen showed 84. 4% ORR which was notably higher than other groups. For resectable gastric cancer patients, the perioperative FLOT regimen led to a significant improvement in patients' OS and PFS versus ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered the optimal option for managing resectable gastric cancer patients.

292. ROLE OF PREOPERATIVE NEOADJUVANT CHEMORADIOTHERAPY FOR LOCALLY ADVANCED BORDERLINE RESECTABLE THORACIC ESOPHAGEAL CANCER

Abstract The results of the JCOG1109 trial indicate that the standard preoperative neoadjuvant therapy is Docetaxel-cisplatin-fluorouracil (DCF) combined chemotherapy. However, appropriate preoperative treatment for borderline resectable cases is still controversial. Preoperative CF-RT therapy with more substantial local control continues to be an option for tumors with a high risk of invading adjacent organs. The study participants were 163 cT3 locally advanced thoracic esophageal cancer patients who underwent preoperative CF-RT therapy followed by radical esophagectomy. The patients were partitioned into 58 borderline resectable cases (cT3.5 group) and 105 resectable cases (cT3 group). We compared the clinicopathological features, surgical results, and survival between the two groups to verify the effectiveness of preoperative CF-RT therapy for cT3.5 cases. SCC was the predominant cancer histological type. Significantly more upper and middle mediastinum cases and fewer lower mediastinum cases in the cT3.5 group (p &amp;lt; 0.0001). There were no significant differences in postoperative complications; anastomotic leakage was 12.1%, and recurrent laryngeal nerve palsy was 32.8%. The pCR rate was significantly lower in the cT3.5 group (p = 0.0219). Nineteen patients (32.8%) in the cT3.5 group relapsed. Details of recurrence were locoregional in 7 patients, distant LN in 1 patient, and distant organ in 11 patients. There were no significant differences in neither 5-year OS nor 5-year DFS between the two groups (p = 0.6547, p = 0.8799; respectively). Borderline resectable esophageal cancer (cT3.5) treated with preoperative CF-RT therapy showed a comparable survival rate even though the pCR rate was lower than that of resectable esophageal cancer (cT3). Preoperative CF-RT therapy may still be a promising treatment for locally advanced thoracic esophageal cancer with suspected invasion of adjacent organs.

A Spectacular Response to the Docetaxel Cisplatin Fluorouracil (TPF) Protocol as Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Lower Lip: A Case Report

Background: Oral-mucosal squamous cell carcinoma (omSCC) is a substantially more aggressive disease that affects the oral mucosa, tongue, floor of mouth, and oropharynx, where it is estimated that between 18.6% and 44% of patients present with nodal disease depending on the subsite. As the lip is a site of anatomical overlap, primary squamous cell carcinoma of the lip (lip SCC) exhibits higher rates of nodal spread, mortality, and poor clinical outcome compared with cutaneous SCC. For patients with locally advanced OSCC, rapid advancements regarding the choice of induction chemotherapy regimen have been made. There is substantial evidence related to the advantage and superiority of three-drug combination of Docetaxel, Cisplatin, and Fluorouracil (TPF) over the doublet regime of Cisplatin and Fluorouracil (PF) used previously as induction chemotherapy (ICT). Case presentation: A 54 years Moroccan women old, who has been accusing, for more than a year, of a neglected painful tumefaction of the lower lip. The clinical examination finds a budding and ulcerous tumefaction of the lower lip and a biopsy of his lip lesion was scheduled. Histopathology report poorly differentiated squamous cell carcinoma. Assessment of extension showed bilateral cervical lymphadenopathy and no distant locations. After a multidisciplinary discussion, the decision was to propose a conservative treatment, namely concurrent radio chemotherapy after induction chemotherapy made of the TPF protocol. The evaluation after 03 cycles of the protocol shows an almost complete disappearance of the apparent tumor with a good tolerance profile. Conclusion: Many analysis demonstrate a statistically significant reduction in locoregional recurrence amongst patients who received Induction chemotherpay despite that she has never provided an improvement to OS for OSCC patients. In the present case, chemotherapy with docetaxel, cisplatin and fluorouracil regimens is considered as an effective induction therapy ...

Surgical stage in sequential therapy of unresectable oral cancer T3-4bN0-3M0: evaluation of treatment results

Introduction. Unresectable oral cancer is an urgent and complex problem in modern oncology. Annually, the proportion of patients with stage III–IV is 35 %, and the one-year mortality rate for this pathology reaches 32 %. Patients with advanced oral tumors usually have a negative prognosis and treatment tactics are limited to radiation therapy (RT), chemoradiation therapy, or sequential therapy, including induction chemotherapy (CT). Polymodal therapy for oral cancer is of particular interest in the treatment of pathology in this area.The study objective – to analyze the results of sequential treatment, including induction CT followed by RT and induction CT followed by surgery and RT in patients with unresectable oral cancer (T3–4bN0–3M0).Materials and methods. This retrospective study included 30 patients (11 women and 19 men) with primary non-resectable squamous cell carcinoma of the oral cavity (T3–4bN0–3M0) who received 2–3 courses of induction chemotherapy (CT) with DCF (docetaxel, cisplatin, 5-fluorouracil). Mean patients’ age was 61.2 years. The first treatment stage included induction CT according to the following scheme: docetaxel (75 mg/m2 /day on day 1) + cisplatin (75 mg/m2 /day on day 1) + 5-fluorouracil (1000 mg/m2 /day on days 1–4) repeated every 21 days. Study participants were divided into 2 groups according to their objective response to CT. Patients with resectable residual tumors have undergone surgery (after induction CT) followed by radical radiation therapy (RT) (induction CT + surgery + RT). Patients with non-resectable residual tumors/no objective response/no complete response after induction CT have undergone radical RT (induction CT + RT).Results. The objective response rate (ORR) to induction CT was 66.6 % (20 / 30). Five out of thirty patients (16.7 %) received no subsequent therapy: 3 individuals developed grade III–IV adverse events, while 2 individuals had progressive disease. One-third of patients (10 / 30; 33.3 %) had surgery followed by RT. Half of patients (15 / 30; 50 %) received RT after induction CT. The two-year relapse-free survival rates in the groups of induction CT + surgery + RT and induction CT + RT was 14 and 16 %, respectively (p = 0.49). The two-year overall survival rates in the same groups were 44 and 38 %, respectively (р = 0.74).Conclusion. Resectability was achieved in 33.3 % (10 / 30) of patients with initially unresectable oral cancer after induction CT. A sequential therapy regimen, including a surgical stage after induction CT, did not demonstrate a statistically significant increase in overall and disease-free survival rates. Sequential multimodal treatment of common oral cancers has some potential, but requires further study to assess its significance.

Second-line treatment after docetaxel, cisplatin and 5-fluorouracil in metastatic squamous cell carcinomas of the anus. Pooled analysis of prospective Epitopes-HPV01 and Epitopes-HPV02 studies

BackgroundSquamous cell carcinoma of the anus (SCCA) is a rare disease often diagnosed at a localised stage. For locally advanced recurrence or metastatic disease, DCF (docetaxel, cisplatin, 5-fluorouracil) demonstrated high efficacy and became one of the standard regimens. However, there is no standard of care in the second line. Patients and methodsIn the Epitopes-HPV01 and Epitopes-HPV02 prospective trials, 115 patients with advanced SCCA were treated with a DCF regimen in the first line. In these studies, second-line data were registered per protocol. ResultsAfter a median follow-up of >40 months, at progression, 73 patients received a second-line (L2) treatment. In this L2 population, median overall survival (mOS) was 13.5 months (95%CI 9.4–19.8), and median progression-free survival (mPFS) was 5.7 months (3.4–7.3) in L2. Fourteen patients presented an oligometastatic progression and were treated with an ablative treatment (surgery or radiotherapy); mOS was 48.3 months (NE–NE), and mPFS was 31.3 months (23.2–NE). Fifty-nine patients received a systemic treatment (chemotherapy or immunotherapy); mOS was 11 months (8.4–15.4) and mPFS was 4.9 months (3.3–7). The most frequent chemotherapy regimens were the reintroduction of DCF, paclitaxel, FOLFIRI and mitomycin plus fluoropyrimidine. No significant difference was observed between regimens (p = 0.26). Six patients received anti-PD1/L1-based immunotherapy. ConclusionSecond-line treatments are effective in patients with SCCA. Ablative treatment is feasible and is probably the best option for patients with oligometastatic progression. If this is not possible, systemic therapy by an anti-PD1/L1 immunotherapy or chemotherapy can be recommended. Reintroduction of DCF, paclitaxel, FOLFIRI or mitomycin-C plus fluoropyrimidine are possible options.

Surgery with hyperthermic intraperitoneal chemotherapy after response to induction chemotherapy in patients with peritoneal metastasis of gastric cancer.

Gastric cancer (GC) with peritoneal metastases (PM) has a dismal prognosis and to date only a few management options have been reported. Of those, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after induction bidirectional intraperitoneal and systemic chemotherapy (BIPSC) appear as a promising treatment option for these patients. Outcome data including safety and efficacy of CRS with radical Gastrectomy and HIPEC after response to combination of laparoscopic HIPEC (LHIPEC) with BIPSC as an induction therapy in patients with PM of GC was evaluated in this retrospective observational study. Diagnostic Laparoscopy was performed in 53 patients with PM of GC who admitted to the Center for Treatment of Peritoneal Surface Malignancies, Istanbul, between 2013 and 2016. Peritoneal cancer index (PCI), ascites status and cytology were determined. The patients underwent LHIPEC and then, BIPSC induction chemotherapy using intraperitoneal docetaxel (30 mg/m2) and cisplatin (30 mg/m2) and intravenous Docetaxel/Cisplatin/5-Fluorouracil (DCF) for 3 cycles. In selected patients, CRS with radical gastrectomy and HIPEC were performed after the response to induction therapy. BIPSC was continued for 3 more cycles with a dose reduction in an adjuvant setting. All LHIPEC procedures were uneventful with Grade 1-2 side effects (11/53, 20,8%). As a response to induction chemotherapy PCI was reduced from 19.6±8 (range, 6-39) to 13.6±9.8 (range, 1-39) (P<0.001). Ascites was detected in 55% (29 out of 53) and cytology was positive in 51% (27 out of 53) of the patients before induction chemotherapy. Ascites was completely abolished and all cytology became negative. Then, 34 of 53 (64.15%) patients underwent CRS with radical gastrectomy and HIPEC. CC0/1 resection was achieved in 22 (64.70%) of patients (P<0.05). The median survival time was 18.9±13.4 (95% CI: 15.2-22.6 months. Combined surgery and HIPEC related mortality occurred in 1 out of 34 patients (2.9%) due to developed diffuse intravascular coagulation at postoperative day 2. Grade 2 operative complications included biliary fistula in one, and duodenal stump leakage in two patients (8.7%). All of the fistula closed with conservative management. The median survival time was 18.9±13.4 months and the median progression-free survival time was 15.6±12.9 with 1-, 2-, and 5-year survival rates of 82.4%, 59% and 17.6% in patients with PM of GC. Multivariate analysis identified high peritoneal cancer index (P=0.000) and complete resection (P<0.05) as independent predictors for better progression-free and overall survival. The best outcomes can be expected with optimal cytoreduction and limited peritoneal dissemination in response to induction chemotherapy. Knowledgeable selection of patients with PM of GC is essential to perform surgery with HIPEC safely with acceptable mortality and morbidity.

Five-year Outcomes of Chemotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Oesophagectomy in Oesophageal Cancer.

Preoperative chemotherapy with surgery is the most effective treatment modality in Japan for advanced oesophageal squamous cell carcinoma (OSCC). We evaluated the long-term outcomes associated with preoperative docetaxel/cisplatin/5-fluorouracil (DCF) administration followed by oesophagectomy in OSCC. Overall, 76 consecutive patients with cStage IB-IIIC OSCC were enrolled. After two cycles of preoperative DCF, oesophagectomy was performed. Survival monitoring was performed and relevant risk factors were analysed. The median follow-up period was 88.3 months. The 5-year overall and recurrence-free survival rates were 51% and 43%, respectively. In the multivariable analysis, cT3 stage [hazard ratio (HR)=1.81, 95% confidence interval (CI)=1.08-6.16], incomplete chemotherapy (HR=2.35, 95% CI=1.37-4.02), poor clinical response (HR=1.82, 95% CI=1.01-3.29), and postoperative complications (HR=2.11, 95% CI=1.14-3.90) were independent predictors of poorer overall survival. The 5-year outcomes of preoperative DCF with oesophagectomy were favourable. Our findings can aid in the formulation of strategies aimed at improving prognosis in OSCC.

Controlling lymph node micrometastases by neoadjuvant chemotherapy affects the prognosis in advanced esophageal squamous cell carcinoma.

The purpose of this study is to determine the clinical significance of micrometastases after neoadjuvant chemotherapy (NAC) and the difference in controlling micrometastases using different NAC regimens in resectable advanced esophageal squamous cell carcinoma (ESCC). We analyzed patients with ESCC who underwent esophagectomy with lymph node dissection after NAC with Adriamycin + cisplatin + 5-fluorouracil (ACF) or docetaxel + cisplatin + 5-fluorouracil (DCF). Micrometastasis was defined as a single isolated cancer cell or cluster of cancer cells on the cervical, recurrent nerve, or abdominal LNs as shown by immunohistochemical staining with anti-cytokeratin antibody (AE1/AE3). The associations between micrometastases, recurrence, prognosis, and regimen differences were investigated. One hundred and one cases (ACF group: 51 cases; DCF group: 50 cases) were analyzed. Micrometastases occurred in 24 patients (23.8%): 17/51 (33.3%) in the ACF group and 7/50 (13.5%) in the DCF group (p = 0.0403). The 5-year recurrence-free survival (RFS) rates for patients without (n = 77) and with (n = 24) micrometastases were 62 and 32%, respectively, (hazard ratio, 2.158; 95% confidence interval, 1.170-3.980; stratified log-rank test, p = 0.0115). A multivariate analysis showed that stage pN1 or higher and micrometastases were significant risk factors affecting RFS. In resectable advanced ESCC, controlling micrometastases in the LNs after NAC varied by regimen and may be associated with preventing ESCC recurrence.

Loss of body weight during neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil as predictive of poor survival of patients with esophageal squamous cell carcinoma.

371 Background: Though neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (DCF) showed a promising efficacy in patients (pts) with resectable esophageal squamous cell carcinoma (ESCC), grade 3 anorexia during the course and body weight loss (BWL) were frequently experienced. BWL is considered as a factor for poor survival in operable cancer pts, however, there is rarely reported of the relationship of BWL during neoadjuvant therapy and survival. Methods: We retrospectively evaluated pts of ESCC withclinical stage II or III, excluding T4, who had received neoadjuvant DCF and esophagectomy (R0 resection) at our institution between April 2010 and December 2018. We define the cut-off level at more than 3% weight reduction (BWL3 group) between before and after of first cycle of DCF. Results: Among the 77 pts who were selected for this analysis, 13 patients showed BWL &gt; 3% (BWLS group), and other 64 pts did not (no-BWL group). The median age, proportions of performance status of 0, cT3 stage, cN2-3 stage and serum albumin lower than normal level in no-BWL and BWL3 group were 65 and 67y.o, 59 and 77%, 88 and 54%, 75 and 69%, 34 and 31%, respectively. There was no significant difference inhistological therapeutic effect (grade 2-3) with 50% in no-BWL and 62% in BWL3 group (P = 0. 549). The incidence of postoperative grade 2 or higher pneumoniawas same in both group (23% vs 17%, P = 0. 695). The median overall survival (OS) was not reached in non-BWL group and 39.5 m in BWL3 group (P = 0.048), respectively. The median progression free survival (PFS) was not reached in non-BWL group and 39.5 m in BWL3 group (P = 0.382), respectively. In multivariate analysis, BWL is independent prognostic factor for OS (hazard ratio [HR] = 11.5, 95%CI: 2.45-53.8, P = 0.002). Conclusions: Our exploratory study demonstrated that body weight loss during first course of neoadjuvant DCF therapy for ESCC patients may be a prognostic factor for survival.

Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Docetaxel/Cisplatin/5-Fluorouracil Followed by Surgery

Background: Preoperative therapy followed by surgery has become the clinical standard for resectable advanced esophageal cancer. Several studies showed that neoadjuvant docetaxel/cisplatin/5-fluorouracil (DCF) resulted in a high response rate and prolonged relapse-free survival, but what constitutes appropriate additional therapy is unknown. Methods: A total of 101 consecutive patients with cStage I B-III esophageal cancer were treated with preoperative DCF between April 2011 and December 2015. After completing 2 cycles of DCF neoadjuvant chemotherapy (NAC), esophagectomy was performed. We investigated prognostic factors and recurrence patterns in patients with resectable esophageal cancer who underwent DCF NAC followed by surgery. Results: Univariate analysis showed that performance status (hazard ratio, HR 2.85; p = 0.033), clinical response (HR 2.16; p = 0.048), pT stage (HR 2.20; p = 0.047), pN stage (HR 5.83; p< 0.001), pathological curability (HR 5.64; p = 0.038), and histological grade (HR 1.92; p = 0.048) were significant factors. Multivariate prognostic analysis revealed that pN stage and pathological curability were significant prognostic factors (HR 11.20; p < 0.001, and HR 27.41; p = 0.007, respectively). In addition, based on the number of metastatic lymph nodes (LNs), the difference in overall survival was the largest between patients with ≤2 and ≥3 metastatic LNs (HR 5.83; p< 0.001). Distant metastatic recurrence increased significantly in patients with 3 or more pathologically confirmed metastatic LNs (p = 0.008). Conclusion: Distant recurrence occurred more frequently and prognosis was poorer in patients with 3 or more pathologically confirmed metastatic LNs; they might need additional systemic therapy.

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma.

To further improve the prognosis of esophageal cancer patients, it is necessary to investigate new treatment strategies. The purposes of this study were to retrospectively assess the safety and efficacy of neoadjuvant chemoradiotherapy (CRT) with docetaxel/cisplatin/5-fluorouracil (DCF) (DCF-RT) in patients with thoracic esophageal squamous cell carcinoma (ESCC). We reviewed 30 thoracic ESCC patients who underwent neoadjuvant DCF-RT followed by esophagectomy, and evaluated the safety and efficacy of DCF-RT. DCF-RT consisted of 40Gy radiation with two courses of intravenous DCF (docetaxel, 30mg/m2/day, day 1; cisplatin, 7mg/m2/day, day 1; 5-FU, 350mg/m2/day, days 1-5 and days 8-12) repeated every 2weeks. Esophagectomy was scheduled 8-10weeks after completion of DCF-RT. Twenty-nine of thirty patients completed radiotherapy; however, 27 of 30 patients required dose reduction of the second cycle of DCF. Complete response (CR), partial response, and stable disease were observed in 7, 11, and 10 patients, respectively. The number of lymph node metastases after DCF-RT was significantly lower than that before DCF-RT (P < 0.0001). Among the 30 patients, pathological CR (pCR) in the primary tumor was observed in 17 patients, and pCRs in both the primary tumor and lymph nodes were observed in 14 patients. The 3-year overall survival rate was 62.2%, and that of patients who experienced pCR was 84%. Neoadjuvant DCF-RT was tolerable and yielded a high pCR rate in ESCC. Therefore, neoadjuvant DCF-RT may confer a survival benefit and may be a candidate neoadjuvant therapy regimen for patients with locally advanced thoracic ESCC.

A case report of pseudo-progression after pembrolizumab in metastatic gastric cancer and a review of immunotherapy in gastroesophageal tumors

In this report, we present the medical history of a 30-year-old male patient with HER2- and PD-L1-negative metastasized adenocarcinoma of the gastric cardia, who received three cycles of pembrolizumab (200 mg every 2 weeks) after the failure of the first-line (1L) treatment with docetaxel, cisplatin, 5‑fluorouracil (DCF). A restaging computed tomography (CT) scan for the chest and abdomen revealed an apparent progressive disease; therefore, the treatment was terminated. Five months after the termination of the treatment, a new CT scan demonstrated a spontaneous treatment response although no treatment was given during this time period, indicating pseudo-progression of the tumor in the first restaging after three cycles of pembrolizumab. This finding is apparently due to the long-term sustainable immunological effects of pembrolizumab. The current report will present this rare case in more detail and summarize the closed and ongoing clinical trials of immunotherapy drugs in gastroesophageal cancer.

Panitumumab in combination with modified docetaxel/cisplatin/5-fluorouracil as first-line treatment in gastric and gastroesophageal junction adenocarcinomas: a multicenter phase II study by the Hellenic Oncology Research Group.

BackgroundA phase I/II study to define the maximum tolerated dose (MTD) of biweekly docetaxel/cisplatin/5-fluorouracil (DCF) plus panitumumab (P), its efficacy, and tolerability as first-line treatment in advanced gastroesophageal cancer.MethodsIn phase I part, patients with unresectable locally advanced or metastatic adenocarcinomas of the stomach or the gastroesophageal junction received cisplatin (40 mg/m2 on day 1), leucovorin (400 mg/m2 on day 1), 5-fluorouracil (400 mg/m2 bolus on day 1), 5-fluorouracil (1000 mg/m2/daycontinuous infusion on days 1-2), and escalated doses of docetaxel (on day 1) plus P (6 mg/kg on day 1) every 2 weeks. In phase II part, patients were treated with DCF/P at the MTD and the primary endpoint was response rate. The expected response rate was set at >40%.ResultsThe MTD for docetaxel in the mDCF/P was defined at 40 mg/m2 and a total of 40 evaluable patients were enrolled in phase II study. One (2.5%) complete and 13 (32.5%) partial responses (overall response rate: 35%), as well as 16 (40%) disease stabilizations were documented. The median progression-free survival was 6.9 months (95% confidence interval [CI] 3.5-10.3) and the median overall survival was 11.3 months (95%CI 7.7-14.8). Grade 3-4 neutropenia occurred in 10 patients (25%) and febrile neutropenia in 2 (5%). Allergic reactions (grade 1-4) occurred in 9 patients (22.5%). There was 1 treatment-related death.ConclusionsmDCF/P combination was feasible, though associated with a poor toxicity profile. However, the study failed to meet its primary endpoint and was terminated prematurely due to futility.

Presence of bone metastases(BM) at diagnosis is associated with poor prognosis and coagulation disorders (CD) in patients (pts) with advanced gastric cancer (AGC).

e15538 Background: The presence of BM in AGC is a relatively uncommon finding and has a poor prognosis [Leporini C. 2015]. At diagnosis the presence of BM occurs in approximately 10-15% of pts with AGC.[Park 2011; Silvestris 2013]. Aim of this study is to describe the main features of pts with AGC and BM at diagnosis and the prognostic implications. Methods: A consecutive series of AGC followed at Cremona Oncology Division from November 2004 to Dicember 2016 and included in three consecutive prospective trials [Dalla Chiesa M. 2011; Tomasello G. 2013], were analyzed. All pts were treated with a modified DCF (docetaxel, cisplatin, fluorouracil) given as a dose-dense regimen, every 14 days. We analyzed pts with BM at diagnosis (BMaD) and pts without BMaD. We evaluated baseline clinical and pathological parameters, the presence of coagulation disorders (CD) together with efficacy measures in the two groups. Results:218 pts with AGC were identified (38 with BMaD and 180 without BMaD).Main pts characteristics and results are reported in the Table below. Conclusions: The presence of BM at diagnosis in pts with AGC is not a rare event (21%) and identifies a population with a significantly poorer outcome and a higher incidence of CD, that need a clinical monitoring of coagulation parameters. More efforts are required to understand the reasons of the different prognosis and to find specific treatments to improve the survival. [Table: see text]

Randomized phase III trial of induction chemotherapy (ICT) with docetaxel-cisplatin-5fluorouracil (DCF) followed by cisplatin-radiotherapy (CRT) or cetuximab-radiotherapy (CetRT) in patients (pts) with locally advanced unresectable head and neck cancer (LAUHNC).

6001Background: CetRT has not been compared with CRT after ICT in phase III. Objective: To compare the impact on overall survival of CRT vs. CetRT after ICT in a Phase III randomized controlled cli...