Camrelizumab combined with FOLFOX as neoadjuvant therapy for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4536-4536
Author(s):  
Ying Liu ◽  
Guangsen Han ◽  
Hongle Li ◽  
Yuzhou Zhao ◽  
Jing Zhuang ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Complete Response ◽  
R0 Resection ◽  
Radical Gastrectomy ◽  
Imaging Evaluation ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Ecog Ps

4536 Background: Neoadjuvant chemotherapy has been demonstrated to improve the pathological complete response(pCR) and 5-year survival rate of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC). Immunotherapy has become a new promising treatment for advanced GC/GEJC. Therefore, we intended to evaluate the safety and efficacy of Camrelizumab (anti-PD-1 antibody) combined with FOLFOX as the neoadjuvant therapy for patients with locally advanced GC/GEJC. Methods: Eligiblepatients were locally advanced GC/GEJC with clinical stage≥T2 and/or positive lymphoglandula confirmed by endoscopic ultrasonography (EUS) and imaging. They received 4 cycles neoadjuvant therapy which including Camrelizumab(200mg ivgtt D1), FOLFOX(Oxaliplatin 85mg/m2 ivgtt D1, 5-Fu 400mg/m2 iv D1, LV 200mg/m2 ivgtt D1, 5-Fu 2.4mg/m2 CIV 46 hours) every 14 days. Imaging evaluation was performed in 2-4 weeks after neoadjuvant therapy. Patients without progression disease (PD) received D2 radical gastrectomy. The primary endpoint was pCR, the secondary endpoints were R0 resection rate and safety. Results: From July 24 2019 to January 31 2020, 16 patients were eligible. The median age was 57 years (29-72 years). A total of 11(69%) males and 5(31%) females, ECOG PS 0 (n=9, 56%), ECOG PS 1 (n=7, 44%). All the patients completed 4 cycles treatment and none of them was confirmed PD by image. One of the patients refused gastrectomy and withdraw from the study. The other 15 patients underwent operation. Unfortunately, intraperitoneal metastases were confirmed in 2 patients during operation. 13 patients received D2 radical gastrectomy and all of them experienced R0 resection. Among the 13 evaluable patients, 1 patient (8%) was observed pCR, 3 patients (23%) experienced TRG1, 10 patients (77%) achieved stage reduction. Notably, 8 patients (62%) had lymphonodus pCR. The grade 3-4 treatment-related AEs were neutropenia (n=3, 19%), leukopenia (n=2, 13%) and anorexia (n=1, 6%). No serious AEs resulted in termination of treatment. Either severe immune-related AEs or treatment-related death was not observed. Conclusions: Camrelizumab combined with FOLFOX as neoadjuvant regimen in patients with locally advanced GC/GEJC showed promising pCR with good tolerance. Clinical trial information: NCT03939962 . [Table: see text]

Camrelizumab combined with FLOFOX as neoadjuvant therapy for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma: Updated results of efficacy and safety.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4036-4036
Author(s):  
Ying Liu ◽  
Guangsen Han ◽  
Hongle Li ◽  
Yuzhou Zhao ◽  
Zhi Li ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
D2 Lymph Node Dissection ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Therapy Strategy ◽  
Grade 3

4036 Background: Although anti-PD-1 antibody in combination with chemotherapy has shown promising antitumor activity in advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC), the evidence of neoadjuvant therapy for locally advanced GC/GEJC is limited. Camrelizumab combined FOLFOX as neoadjuvant therapy for resectable locally advanced GC/GEJC was a prospective, single-arm, phase 2 study we conducted. Here, we updated the results of efficacy and safety of this study. Methods: Patients confirmed by endoscopic ultrasonography (EUS) and imaging with clinical stage≥T2 and/or positive lymph nodes were enrolled. They received 4 cycles of camrelizumab (200mg ivgtt on day1, q2w) plus FOLFOX (oxaliplatin 85mg/m2 ivgtt, LV 200mg/m2 ivgtt, 5-Fu 400mg/m2 iv followed by 2.4mg/m2 CIV 46 hours on day 1, q2w) as neoadjuvant therapy. Then patients without disease progression evaluated by imaging underwent gastrectomy of D2 lymph node dissection. The primary endpoint was pCR, the secondary endpoints were R0 resection rate and safety. Results: Between Jul 24 2019 and Nov 30 2020, 49 patients were enrolled. The median age was 57 years (29-72 years). All patients completed 4 cycles treatment. Unfortunately, 2 of them were confirmed PD by imaging. In addition, two patients refused gastrectomy and withdrew from the study. Eventually, 45 patients underwent gastrectomy, of which 3 patients had intraperitoneal metastases during the operation. A total of 42 patients were evaluable, all of them gained R0 resection (100%), 4 patients (10%) achieved pCR and 10 patients (24%) reached TRG1. Among the patients experienced pCR, one of them was Her-2 positive, one was MSI-H, the rest two of them were PD-L1-positive (CPS≥10). The most common ≥grade 3 adverse events (AEs) were neutropenia (35%) and leukopenia (16%). Only 1 patient (2%) experienced grade 3 immune-related AEs of alanine aminotransferase and aspartate aminotransferase increase. No serious AEs resulted in termination of treatment or death. Conclusions: Camrelizumab combined with FOLFOX was an effective and safe neoadjuvant therapy strategy for patients with resectable locally advanced GC/GEJC. Furthermore, the analysis of biomarkers with clinical benefits is undergoing. Clinical trial information: NCT03939962. [Table: see text]

Association of total neoadjuvant therapy with favorable clinical outcomes in patients with locally advanced esophageal and gastroesophageal junction adenocarcinomas (LA-GEJ CA).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 231-231
Author(s):  
Lauren Jurkowski ◽  
Aditya Varnam Shreenivas ◽  
Sakti Chakrabarti ◽  
Mandana Kamgar ◽  
James P. Thomas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Clinical Outcomes ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Metabolic Imaging ◽  
R0 Resection ◽  
Curative Intent

231 Background: Both peri-operative chemotherapy and neoadjuvant chemoradiation have been shown to improve outcomes in patients (pts) with LA-GEJ CA compared to surgery alone. Rates of post-operative chemotherapy delivery remain suboptimal. Total neo-adjuvant therapy (TNT) in LA-GEJ CA - induction chemotherapy (IC) followed by concurrent chemoradiation (CRT) - may improve systematic delivery of neoadjuvant therapy and result in favorable clinical outcomes. Methods: We retrospectively reviewed medical records of 135 pts with LA-GEJ CA at our institution between 2/2007 and 11/2019; pertinent clinical data were abstracted with Institutional Review Board approval. Patients treated with IC and curative-intent CRT with ≥40 Gy dose of radiation for adenocarcinoma were included in this analysis (N = 59). Doublet or triplet IC regimens utilizing 5-Flurouracil(5-FU), Cisplatin/Oxaliplatin and Docetaxel were commonly administered while combinations of Carboplatin +Paclitaxel or 5-FU + Oxaliplatin were used in CRT. Clinical complete response (CCR) was defined as metabolic imaging and endoscopic biopsies negative for residual malignancy after completion of TNT. Patients were followed from diagnosis to recurrence and overall survival. Survival probabilities were estimated using the Kaplan-Meier method and compared between groups using a log-rank test. Results: Out of 59 evaluable pts, 69% were clinical stage T3, 71% were node positive. 37 pts (63%) underwent surgery, R0 resection rate was 89% (33/37), pathologic complete response (pCR) rate was 19% (7/37). Among the pts who did not undergo surgery, 41% (9/22) opted to forego surgery since they attained a CCR. For the entire cohort, median Disease-Free Survival (mDFS), median Overall Survival (mOS), and 3-yr OS were 2.4 yrs, 4.7 yrs, and 67% respectively. Pts who did not undergo surgery had a mDFS, mOS, and 3-yr OS of 1.5 yrs, 4.2 yrs, and 59% respectively. Median DFS, mOS, and 3-yr OS of patients who underwent surgery were 3.5 yrs, 5.8 yrs and 72% respectively. Patients who achieved a CCR and opted to forego surgery (N = 9) had a 3 -yr DFS of 42% vs 83% for pts (N = 7) who demonstrated a pCR after curative intent tri-modality therapy. (P = 0.0099) Interestingly, the same group that achieved CCR and opted out of surgery had 3yr OS of 89% vs 83% of those who demonstrated a pCR (p = 0.0042). Conclusions: TNT for pts with LA-GEJ CA is associated with high rates of R0 resection as well as excellent DFS and OS compared to historical controls, warranting prospective evaluation. The remarkable DFS and OS in patients who opted to forego surgery due to achieving CCR is reflective of the local and systemic control rendered by this approach. Careful characterization and close longitudinal follow-up of patients who achieve CCR may help identify a subgroup of LA-GEJ CA pts who may benefit from surgery sparing approaches.

Efficacy and safety of camrelizumab combined with FOLFOX as neoadjuvant therapy for patients with resectable locally advanced gastric and gastroesophageal junction adenocarcinoma who received D2 radical gastrectomy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16549-e16549
Author(s):  
Yuzhou Zhao ◽  
Guangsen Han ◽  
Jing Zhuang ◽  
Zhimeng Li ◽  
Gangcheng Wang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Neoadjuvant Therapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
R0 Resection ◽  
Lymph Node Yield ◽  
D2 Lymph Node Dissection ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
The Mean

e16549 Background: Neoadjuvant chemotherapy for patients with locally advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC) can improve the overall survival without increasing operation risk. Nowadays, immunotherapy has become a new promising neoadjuvant treatment. Therefore, we intended to evaluate the safety and efficacy of camrelizumab (anti-PD-1 antibody) combined with FOLFOX as the neoadjuvant therapy for patients with locally advanced GC/GEJC who received D2 radical gastrectomy. Methods: Patients who were diagnosed as resectable locally advanced GC/GEJC received the neoadjuvant treatment of camrelizumab and FOLFOX every 2 weeks for 4 cycles. Imaging evaluation was performed in 2-4 weeks after neoadjuvant therapy. Patients who had no progression disease (PD) were recruited. Eligible patients underwent gastrectomy with D2 lymph node dissection through laparotomy or laparoscopic surgery. The primary end points were safety and R0 resection rate. Results: From July 24 2019 to January 31 2020, 15 patients were recruited. The mean age was 57 years. A total of 10(67%) were males and 5(33%) were females. According to AJCC 8th, cT3 and cT4 were confirmed in 7(47%) patients and 8(53%) patients, N1 and N2 in 7(47%) patients and 8(53%) patients, respectively. During operation, intraperitoneal metastases were found in 2 patients. Of the 13 surgeries, only 2 were laparoscopic and the others were laparotomy. The surgical procedures included Roux-en-Y (9, 69.2%), Billroth II (1, 7.7%) and jejunum interposition (3, 23.1%). Thirteen patients underwent gastrectomy with D2 lymph node dissection and all of them were confirmed R0 resection by postoperative pathology results. The mean lymph node yield was 44.1±13.2 nodes, positive lymph node yield was 1.8±2.8 nodes. Duration time of surgery was 186.5±45.5 minutes, mean blood loss was 219.2±109 ml during the operation. Mean hospital stays were 13.2±2.4 days. Only 1 patient experienced grade 3 pneumonia. Neither serious intraoperative complications nor immune-related adverse events both prior and post operation were observed. There was no treatment-related death. Conclusions: Camrelizumab combined with FLOFOX as neoadjuvant treatment for patients with locally advanced GC/GEJC showed acceptable toxicity and promising efficacy with low complications and mortality. Clinical trial information: NCT03939962 .

Efficacy and safety of camrelizumab combined with FLOT versus FLOT alone as neoadjuvant therapy in patients with resectable locally advanced gastric and gastroesophageal junction adenocarcinoma who received D2 radical gastrectomy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16020-e16020
Author(s):  
Ning Liu ◽  
Zimin Liu ◽  
Yanbing Zhou ◽  
Zhaojian Niu ◽  
Haitao Jiang ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Intraoperative Complications ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Tumour Regression ◽  
R0 Resection ◽  
Resection Rate ◽  
Tumour Regression Grade ◽  
Ecog Ps

e16020 Background: Docetaxel-based neoadjuvant chemotherapy has been suggested to be beneficial in patients with locally advanced gastric and gastro-oesophageal junction cancer (GC/GEJC). And immunotherapy also show promising treatment efficacy for advanced GC/GEJC. Here we compared the safety and efficacy of camrelizumab combined with chemotherapy versus chemotherapy alone as the neoadjuvant therapy for patients with resectable locally advanced GC/GEJC. Methods: Eligible patients diagnosed as resectable locally advanced GC/GEJC were randomized to receive neoadjuvant treatment, in arm A, the patients received FLOT alone (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2600 mg/m², every 2 weeks), in arm B, the patients received FLOT combined with camrelizumab(camrelizumab 200mg intravenously every 3 weeks). Eligible patients underwent gastrectomy with D2 lymph node dissection. The primary end point of this trial was pCR rate and R0 resection rate, and the secondary end points were ORR,PFS, OS and safety profile. Results: From January 15 2020 to January 15 2021, 24 patients were recruited (11 patients in arm A and 13 patients in arm B). 19 patients had completed planned neoadjuvant treatment for 4 cycles (9 pts in the arm A, 10 ptsin the arm B). Two patients in the arm A were waiting for gastrectomy. This analysis was based on the 17 pts. In the arm A, the median age was 61 years (47-72 years) and a total of 5 males and 4 females, ECOG PS 0 (n = 1), ECOG PS 1 (n = 8). In the arm B, the median age was 63 years (57-71 years) and a total of 9 males and 1 females, all patients with ECOG PS 1. The R0 resection rate was high in arm B compared with arm A (10/10,100% vs. 5/7, 71.4%). No pCR were observed in the two arms. Tumour regression grade were as follows:TRG1 [arm A 0% (0/7), arm B 10% (1/10)], TRG2 [arm A 43% (3/7), arm B 60% (6/10)], TRG3 [arm A 29% (2/7), arm B 30% (3/10)].There was a significantly higher proportion of patients achieved a postoperative ypN0 in the arm B than arm A(60% vs 0%), which had preoperative clinical stage cT3-4N+M0. Postoperative pathologic staging was as follows: ypT1 [arm A 14% (1/7); armB 30% (3/10)]. ypT2 [armA 0% (0/7); armB 30% (3/10)]. ypT3 [arm A 29% (2/7); arm B 20% (2/10)]. ypT4 [armA 29% (2/7); armB 20% (2/10)]. Neither serious intraoperative complications nor immune-related adverse events were observed during perioperation. Treatment-related AEs neutropenia and leukopenia were manageable and there was no treatment-related death. Conclusions: Camrelizumab combined with FLOT showed promising efficacy as neoadjuvant treatment for patients with locally advanced gastric or GEJ adenocarcinoma, with low complications and acceptable toxicity. Clinical trial information: ChiCTR2000030610.

Camrelizumab combined with albumin paclitaxel and cisplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16021-e16021
Author(s):  
Huilai Lv ◽  
Yang Tian ◽  
Chao Huang ◽  
Zhenhua Li ◽  
Ziqiang Tian
Keyword(s):  
Surgical Treatment ◽  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Objective Response ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
R0 Resection ◽  
Resection Rate

e16021 Background: The pathologic complete response (pCR) rate is improved by neoadjuvant therapy in locally advanced ESCC, but occurs less than 10% of patients(pts) with neoadjuvant chemotherapy agents. Immunotherapy has become a new promising treatment. Camrelizumab (anti-PD-1) is standard of care as second-line therapy for advanced ESCC in China. Therefore, we intended to evaluate the efficacy and safety of Camrelizumab combined with albumin paclitaxel and cisplatin as neoadjuvant therapy for pts with locally advanced ESCC. Methods: We retrospectively analysed locally advanced ESCC pts with clinical stage Ⅱ-ⅣA. Eligible pts were aged 18–75 years with no prior any therapy. Pts received 2-4 cycles neoadjuvant therapy which including Camrelizumab (200mg IV q3w), albumin paclitaxel (260 mg/m2 IV q3w) and cisplatin (75 mg/m2 IV q3w). Surgery was performed 4-6 weeks after neoadjuvant therapy. The primary endpoint was pCR, the secondary endpoints were major pathologic response (MPR), R0 resection rate, objective response rate (ORR), disease-free survival (DFS) and safety. Results: From Jul 27 2019 to Sep 26 2020,16 pts were enrolled and available evaluated. 8 pts (50%) had clinical complete response (cCR), and the ORR was 87.5% (14/16). All pts underwent surgery and surgical treatment was not delayed. The pCR was 43.8% (7/16), MPR was 75% (12/16). Notably, R0 resection rate was 100% (16/16). None of 16 pts progressed, the DFS was not yet achieved. The average intraoperative blood loss was 131ml (100-200ml) and the average hospitalization time after operation was 14 days (11-21 days). No patient developed anastomotic leak and other surgical treatment-related toxicity. The grade 1-2 treatment-related AEs were reactive cutaneous capillary endothelial proliferation (RCCEP) (n = 3,18.8%), weakness (n = 2, 12.5%), Myelosuppression (n = 1, 6.2%) and hypothyroidism (n = 1, 6.2%). No serious AEs resulted in termination of treatment, and treatment-related death was not observed. Conclusions: The addition of camrelizumab to albumin paclitaxel and carboplatin was demonstrated encouraging clinical efficacy and acceptable safety as neoadjuvant therapy, and might be a favorable option for pts with locally advanced ESCC. Further registered clinical trials are expected.

Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4050-4050
Author(s):  
Hongli Li ◽  
Jingyu Deng ◽  
Shaohua Ge ◽  
Fenglin Zang ◽  
Le Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Death Receptor ◽  
Disease Free Survival ◽  
Complete Response ◽  
R0 Resection ◽  
Combination Regimen

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

scholarly journals Induction Chemotherapy Followed by Concurrent Chemo-Radiotherapy for Locally Advanced Gastro-Esophageal and Gastric Carcinoma

2021 ◽  
pp. 35-44
Author(s):  
Nora Shaband ◽  
Niveen Abo-Touk ◽  
Mohamed Elawadi ◽  
Saleh Ta-Ema
Keyword(s):  
Induction Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Esophageal Stenosis ◽  
University Hospital ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Gastroesophageal Adenocarcinoma

Aims: To assess the safety and efficacy of chemo-radiotherapy before radical surgery in locally advanced gastric and gastroesophageal adenocarcinoma. Study Design: This was a prospective phase Ⅱ single arm study. Place and Duration of Study: Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Mansoura, Egypt, between May 2017 and June 2019. Methodology: Patients with pathologically proven gastric or gastroesophageal junction adenocarcinoma are included. They received one cycle of induction chemotherapy paclitaxel-carboplatin, [paclitaxel dose of 175 mg/m2, carboplatin dose of (AUC: 5)], followed by CCRT [RT 45 Gy over 25 fractions over 5 weeks concurrent with weekly paclitaxel at a dose of 50 mg/m2, carboplatin at a dose of (AUC: 2)], followed by surgery and 2 cycles of paclitaxel-carboplatin for responders. Results: The study included 24 patients. Most of the patients were diagnosed at stage III (83.3%). There were no major side effects of the induction chemotherapy cycle. There were no reported grade 3 or 4 toxicities for the CCRT. Only two patients suffered from late radiation toxicities (distal esophageal stenosis). Pathological complete response was achieved in seven patients (31.8%). Twenty-two patients had surgical resection with a 95% resection margin zero. The median follow-up time was 22.5 months. The median progression-free survival (PFS) and overall survival (OS) were 23, 23.5 months, respectively. Conclusion: The preliminary data suggested good efficacy of the studied treatment design with acceptable adverse-event rates, however a larger multicentric phase 3 trial with a longer follow-up duration is recommended.

Phase I trial of neoadjuvant concurrent chemoradiotherapy with S-1 and weekly irinotecan in locally advanced rectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14543-14543
Author(s):  
J. Ahn ◽  
H. Choi ◽  
S. Cheon ◽  
S. Shin ◽  
K. Keum ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase I ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
R0 Resection ◽  
Dose Levels

14543 Background: S-1 is a novel, orally administered 5-FU analogue and is known of radiosensitizer. The aim of this study was to establish the feasibility and efficacy of S-1 in combination with weekly irionotecan with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer. Methods: Clinical stage T3–4 or N+(on MRI) rectal adenocarcinoma patients received weekly irinotecan 40mg/m2(day1,8,15,22,29) and S-1 at dose levels of 40, 50, 60 and 70mg/m2 (5days a week from day 1 to 38) according to phase I methodology. Concurrently conventional RT was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 50.4 (45 + 5.4)Gy. Surgery was performed 4–8 weeks following completion of chemoradiation. Results: A total 16 patients (10M/7F, median age 46 years, ECOG PS0–1) were enrolled between August 2005 and July 2006. One pt withdrew the consent during CCRT. Dose-limiting toxicity (DLT) occurred at 50mg/m2 of S-1 in one of six pts (G4 cerebral infarction). At dose of 60, 70mg/m2 of S-1, no DLT occurred. G3/4 toxicties were rare. Fifthteen pts underwent surgery and R0 resection was achieved in 13 pts. Four pts (25.0%) had a pathological complete response. Conclusions: The recommended dose (RD) for further study is S-1 70mg/m2 with irinotecan and radiotherapy. Neoadjuvant S-1/irinotecan/RT is feasible and well tolerated. Phase II trial is being conducted. No significant financial relationships to disclose.

Weekly cetuximab (CET) plus oxaliplatin (OX), infusional 5-fluorouracil (5-FU) and radiation therapy (RT) as neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC): A phase I study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15507-e15507
Author(s):  
F. Lordick ◽  
C. Meyer zum Büschenfelde ◽  
P. Thuss-Patience ◽  
N. Röthling ◽  
H. Geinitz ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
R0 Resection ◽  
Moderate Anemia ◽  
Hand Foot Syndrome ◽  
Ecog Ps

e15507 Background: CET, a chimeric monoclonal IgG1 antibody that targets the epidermal growth factor receptor (EGFR), has proven activity in a variety of SCC models in vitro and in vivo and has also been shown to enhance the activity of both chemo- and radiotherapy. Methods: Patients (pts) with locally advanced ESCC received CET for 2 weeks at an initial dose of 400mg/m2 (d - 15) i.v. followed by 250mg/m2(d -8) before they started a neoadjuvant dose escalation regimen. Pts received weekly CET 250mg/m2 plus RT 25 x 1.8 Gy (cumulative dose 45 Gy) d1–33. Cohort 1–3 received escalating doses of OX 45–50 mg/m2 d1,8,22,29 plus 5-FU 180–200–225 mg/m2/d; d1–5,8–12,15–19,22–26,29–33). Surgery was scheduled 4–6 weeks after RT. Toxicity was assessed according to NCI-CTC. Response was categorized according to the histopathologic score. Results: 15 pts were enrolled (2 female, 13 male; mean age 62 years, ECOG-PS 0 or 1). All pts had locally advanced SCC (uT2–4, cNx, cM0–1a) of the cervical (n=1), the upper (n=5) or the distal (n=7) esophagus. 6 pts were treated in cohort 1 and 3 pts in cohort 2 without any dose limiting toxicity (DLT). Of 6 pts treated in cohort 3, 1 pt developed grade 3 diarrhea and mucositis. All other observed toxicities were mild or moderate: anemia n=12, neutropenia n=2, thrombocytopenia n=3, nausea/vomiting n=8, mucositis n=6, diarrhea n=4, neuropathy n=4, hand-foot-syndrome n=8, skin rash n=14, no infection and no infusion-related reactions were observed. 12 pts underwent abdomino-thoracic esophagectomy with no postop. mortality; 3 pts were not resected. 8/12 resected pts had an R0 resection (67%) and 4 pts (33%) achieved a histopathological complete response (score 1a). Conclusions: 2 weeks of CET (400mg/m2 and 250mg/m2) followed by weekly CET (250mg/m2) plus OX 50mg/m2 d1,8,22,29, 5-FU 225 mg/m2/d d1–5,8–12,15–19,22–26,29–33 and RT 45 Gy (1.8Gy/f) was shown to be safe as neoadjuvant treatment for locally advanced ESCC. The anti-tumor activity of this regimen is promising and is being further investigated in an ongoing phase II study. [Table: see text]

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