Neoadjuvant chemoradiotherapy with 5-fluorouracil-cisplatin combined with cetuximab in patients with resectable locally advanced esophageal carcinoma: A prospective phase I/II trial (FFCD-PRODIGE 3)—Preliminary phase II results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4091-4091
Author(s):  
Laetitia Dahan ◽  
Christophe Mariette ◽  
Marc Ychou ◽  
Tan Dat Nguyen ◽  
Rosine Guimbaud ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Phase I ◽  
Cell Carcinoma ◽  
Dose Level ◽  
Phase Ii ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Stage Ii ◽  
Phase Iii

4091 Background: Chemoradiotherapy (CRT) for locally advanced esophageal cancer is based on 5FU combined with cisplatin. The anti-EGFR antibody cetuximab increases the efficacy of RT-based regimen for patients (pts) with cancer of the head and neck. This phase I/II trial was evaluating MTD, safety and pathologic complete response (pCR) rate of the combination of cetuximab with platinum-based CRT in esophageal cancer. Methods: Inclusion criteria: squamous cell carcinoma or adenocarcinoma of the esophagus, stage II-III, WHO PS 0-1. A radiotherapy of 45 grays (1.8 Gy/25F) was given over 5 weeks. During phase I, four patients experienced limited toxicity to dose level 0, and treatment was desescalated to dose level -1: weekly cetuximab (400 mg/m2 one week before start of radiotherapy and 250 mg/m2 during radiotherapy), and 5 FU (500 mg/m2 per day D1-D4) combined with cisplatin (40 mg/m2 D1) on week 1 and 5. Nine pCR over 27 resections were needed to show a pCR rate>20% (α=5%, power = 90% ). Thirty three patients were included in the phase II. Results: From 07-2007 to 01-2011, 33 pts were enrolled, 20 squamous cell carcinoma (60.6%), 13 adenocarcinoma (39.4%), 25 (75.8%) stage III and 8 (24.2%) stage II. Among 32 pts who received CRT, the main grade 3-4 toxicities were esophagitis (4 pts), leucopenia (1 pt), anaphylaxis reaction (1 pt), rash (1 pt). Resection was achieved in 27 pts (25 R0)/31 who underwent surgery. Complete or near complete pathologic response (TRG grades 1 and 2 to Mandard) was achieved respectively in 5 (18.5%) and 6 (22.2%) pts. There were 4 deaths at 30 days post surgery. Severe postoperative complications were pulmonary complications (8), anastomotic stricture (4), gastric necrosis (1) and infection (7). The median overall survival was 15.7 months [11.01-.], and the median relapse free survival was 13.7 months [5.47-.]. Conclusions: Adding cetuximab to preoperative chemoradiotherapy including 5FU and cisplatin did not increase pCR. The recommended dose level of chemotherapy determined during phase I could explain those disappointing results. We won’t initiate a phase III trial.

A phase II study of single agent OSI-7904L in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17005-e17005
Author(s):  
B. Hough ◽  
M. Posner ◽  
C. Chung ◽  
J. Hainsworth ◽  
J. Horan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Squamous Cell ◽  
Performance Status ◽  
Single Agent ◽  
Stage Ii ◽  
Recurrent Squamous Cell Carcinoma

e17005 Background: Given the limited efficacy and relative toxicity of chemotherapy for metastatic or recurrent squamous cell carcinoma of the head and neck, further research is needed to both increase the efficacy and decrease the toxicity of treatment. OSI-7904L is a novel liposomal formulation of a non-competitive thymidylate synthase inhibitor. In a phase I study, 12 mg/m2 dosing given every 21 days was both feasible and well tolerated. Methods: This multi-center, two-stage, phase II trial was designed to assess the efficacy and toxicity of OSI-7904L in patients with advanced, refractory SCCHN. A total of 41 patients were to be enrolled by completion of stage II. Enrollment was limited to patients with histologically proven squamous histology, locally recurrent and/or metastatic disease, with no more than one prior chemotherapy regimen. Patients were required to have a performance status of ≤ 2, predicted life expectancy of at least three months and adequate hematopoietic, hepatic and renal function. Efficacy was assessed according to RECIST guidelines, and toxicity was evaluated per CTC AE 3.0. Results: Ten patients enrolled in stage 1. Median age was 60 (range 42–66). Nine were evaluable for response assessment with one withdrawn after one cycle due to a grade 4 papular rash. There were no objective responses while 4 of the 10 patients had stable disease during their first restaging. Median time to progression was 2.5 months for the 9 evaluable patients. Besides the one grade 4 dermatologic reaction, other toxicities were grade 3 fatigue and dehydration, and grade 2 anorexia. Assuming an expected 20% response rate required to initiate enrollment in stage II, the probability of the tenth patient being a responder was less than 3%, thus the study was closed due to lack of response in this population. Conclusions: OSI-7904L was well tolerated similar to the phase I data, but did not demonstrate efficacy in metastatic or recurrent HNSCC patients. Further study of this drug as a single-agent with the current dosing regimen is not recommended. [Table: see text]

Phase I Study of C-TPF in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

2009 ◽  
Vol 27 (27) ◽  
pp. 4448-4453 ◽  
Author(s):  
Robert I. Haddad ◽  
Roy B. Tishler ◽  
Charles Norris ◽  
Laura Goguen ◽  
Tracy A. Balboni ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Dose Level ◽  
Squamous Cell ◽  
Phase I Study ◽  
Locally Advanced ◽  
Advanced Squamous Cell Carcinoma ◽  
Gi Toxicity

PurposePhase I study to determine the maximum tolerated dose (MTD) of fluorouracil (FU) in the docetaxel/cisplatin/FU (TPF) regimen when combined with cetuximab (C) for induction treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN).Patients and MethodsPatients with previously untreated SCCHN were enrolled. FU cohorts were 700, 850, and 1,000 mg/m2/d for 4 days via continuous infusion. TPF given every 3 weeks for three cycles and C was given weekly for a total of 9 weeks, starting on day 1 of TPF. All patients received chemoradiotherapy after C-TPF.ResultsA total of 30 patients were enrolled and 28 were assessable. The median age was 57 years, 92% had stage 4 disease, 71% were oropharynx, and 100% had a performance status of 0. No dose-limiting toxicity (DLT) was encountered on dose levels 1 and 2. At dose level 3 of 1000 mg/m2, one DLT was encountered and three more patients were enrolled with no DLTs. In the expansion cohort at the MTD, three DLT's were encountered. The decision was made to decrease the FU from 1,000 mg/m2to dose level 2 of 850 mg/m2. A total of 13 patients were enrolled at the MTD of 850 mg/m2. The number of average weeks that C was delivered was seven of nine planned.ConclusionC-TPF appears to be safe and feasible as given in this study. GI toxicity (mucositis, enteritis, and diarrhea) appears to be the major combined DLT. Reducing the FU in TPF to 850 mg/m2reduces GI toxicity and is the recommended phase II dose.

scholarly journals Phase II study of bevacizumab in combination with docetaxel and radiation in locally advanced squamous cell carcinoma of the head and neck

Head & Neck ◽  
2014 ◽  
Vol 37 (11) ◽  
pp. 1665-1671 ◽  
Author(s):  
Min Yao ◽  
Nicholas Galanopoulos ◽  
Pierre Lavertu ◽  
Pingfu Fu ◽  
Michael Gibson ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Squamous Cell ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Squamous Cell Carcinoma

659 AN SINGLE-ARM OPEN-LABEL PHASE II STUDY OF CAMRELIZUMAB PLUS APATINIB AS SECOND-LINE TREATMENT FOR ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Qingxia Fan ◽  
Junsheng Wang ◽  
Tao Wu ◽  
Yonggui Hong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Squamous Cell ◽  
Objective Response ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line

Abstract   Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed. Methods This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors. Conclusion This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.

Phase I Trial of Escalating-Dose Irinotecan Given Weekly With Cisplatin and Concurrent Radiotherapy in Locally Advanced Esophageal Cancer

2003 ◽  
Vol 21 (15) ◽  
pp. 2926-2932 ◽  
Author(s):  
David H. Ilson ◽  
Manjit Bains ◽  
David P. Kelsen ◽  
Eileen O’Reilly ◽  
Martin Karpeh ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase I ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Phase Iii ◽  
Concurrent Radiotherapy ◽  
Minimal Toxicity ◽  
Grade 3

Purpose: To identify the maximum-tolerated dose and dose-limiting toxicity (DLT) of weekly irinotecan combined with cisplatin and radiation in esophageal cancer. Patients and Methods: Nineteen patients with clinical stage II to III esophageal squamous cell or adenocarcinoma were treated on this phase I trial. Induction chemotherapy with weekly cisplatin 30 mg/m2 and irinotecan 65 mg/m2 was administered for four treatments during weeks 1 to 5. Radiotherapy was delivered weeks 8 to 13 in 1.8-Gy daily fractions to a dose of 50.4 Gy. Cisplatin 30 mg/m2 and escalating-dose irinotecan (40, 50, 65, and 80 mg/m2) were administered on days 1, 8, 22, and 29 of radiotherapy. DLT was defined as a 2-week delay in radiotherapy for grade 3 to 4 toxicity. Results: Minimal toxicity was observed during chemoradiotherapy, with no grade 3 or 4 esophagitis, diarrhea, or stomatitis. DLT caused by myelosuppression was seen in two of six patients treated at the 80-mg/m2 dose level, thus irinotecan 65 mg/m2 was defined as the recommended phase II dose. Dysphagia improved or resolved after induction chemotherapy in 13 (81%) of 16 patients who reported dysphagia before therapy. Only one patient (5%) required a feeding tube. Six complete responses (32%) were observed, including four pathologic complete responses in 15 patients selected to undergo surgery (27%). Conclusion: Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered.

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