Phase-2 study of neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma: The Radio-Xelox study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13549-13549 ◽  
Author(s):  
M. Salimichokami ◽  
M. Vafai ◽  
S. Derakhshani ◽  
S. Aminian ◽  
A. A. Vaheed
Keyword(s):  
Radiation Treatment ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Neoadjuvant Chemoradiation ◽  
Severe Adverse Effect ◽  
Preoperative Radiation ◽  
Systemic Spread ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Pathologic Complete Remission

13549 Background: Neoadjuvant Radiation treatment has been shown in many studies to decrease the incidence of loco-regional relapse in pts with locally-advanced Rectal Adenocarcinoma. Capecitabine and Oxaliplatin are both effective antineoplastic drugs in Colorectal Adenocarcinoma. They also have radiosensitizing effects. Hence,it is rational to combine these agents in association with radiotherapy,to achieve local controle and prevent systemic spread of the cancer. Methods: Thirty-eight pts with Rectal Adenocarcinoma (T3-T4 and/or N+) received radiation treatment (2.0 Gy, 5days a wk over 5 wks,total dose 50 Gy) plus oral Capecitabine at 600 mg/m2 twice a day and iv Oxaliplatin at 35 mg/m2 once weekly × 5wks. Surgery was performed 6wks post completion of XRT. Our end points were safety/feasibility and response/efficacy as demonstrable by the rate of pathologic complete remission (path-CR). Results: Seven pts (20%) acheived path-CR. Diarrhea was the most important severe adverse effect (in 25% of pts). fourteen pts (40%) showed good regression (very few cancer cells in fibronecrotic tissue Dworak grade 3). The remaining 17 pts showed less favorable regression or no significant change. Conclusions: Preoperative Radiation treatment plus chemotherapy with XELOX regimen is feasible, safe and effective with an impressive rate of path-CR in locoregionally advanced Rectal Adenocarcinoma. No significant financial relationships to disclose.

Randomized phase II trial of preoperative chemoradiotherapy with or without cetuximab in locally advanced rectal adenocarcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 537-537 ◽  
Author(s):  
A. David McCollum ◽  
Darren M. Kocs ◽  
Punit Chadha ◽  
Michael A. Monticelli ◽  
Thomas E. Boyd ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Radiation ◽  
Pelvic Radiotherapy ◽  
Recurrence Rates ◽  
Grade 3

537 Background: Treatment for locally advanced rectal cancer (LARC) includes preoperative radiation concurrent with fluoropyrimidine chemotherapy (CRT). Local recurrence is a problem. Cetuximab is active in colorectal cancer and is effective with radiotherapy in other diseases. This study evaluated the pathologic response rate for LARC treated with preoperative chemoradiotherapy w/wo cetuximab. Methods: LARC (T3/4 or LN+, M0) pts were randomized to Arm1/Arm2. Arm 1 received standard pelvic radiotherapy (5040-5400cGy in daily fractions) with continuous infusional 5-FU (225mg/m2/day); Arm 2 received identical chemoradiotherapy + concurrent cetuximab (400mg/m2 initial dose) 1 week before pelvic radiotherapy, followed by 250mg/m2 weekly for the duration of chemoradiotherapy. After study treatment completion, pts were re-evaluated clinically and radiographically for clinical response. After 6-8 weeks, patients underwent surgical resection. The primary end point was pathologic CR (pCR), and secondary endpoints included ORR, RFS, OS, and local recurrence rates. Results: 139 pts were enrolled (Arm 1=69/Arm2=70); Arm1/Arm2 median age 61/55 yrs, and stage II and III 59%, 39%/40%, 60%. In 124 postsurgery pts, pCR occurred in 17 Arm 1 pts (28.3%, 95% CI 17.5-41.4) and 17 Arm 2 pts (26.6%, 95% CI 16.3-39.1); TRG postsurgery was similar between treatment arms (Table). Grade 3 and 4 toxicities were largely nonhematologic: diarrhea 16%/22%, rash 0%/12%, dehydration 5%/8%, mucositis 5%/6%. The 5-yr RFS for Arm1/Arm2 was 61%/65%, 5-yr OS was 66%/83%, local recurrence was 3%/4%. Conclusions: The addition of cetuximab to preoperative CRT for LARC was associated with increased but manageable toxicities. pCR rates were similar between treatment arms, as were survival statistics and local recurrence rates. No association was found between KRAS status and pCR. Clinical trial information: NCT00527111. [Table: see text]

Combined preoperative radiation and mitomycin/5-fluorouracil treatment for locally advanced rectal adenocarcinoma

1998 ◽  
Vol 187 (2) ◽  
pp. 164-170 ◽  
Author(s):  
Stephen J Burke ◽  
Bernard A Percarpio ◽  
David C Knight ◽  
Edward M Kwasnik
Keyword(s):  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Preoperative Radiation

scholarly journals Impact of histological subtype on treatment outcomes in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation

2018 ◽  
Vol 57 (12) ◽  
pp. 1721-1723
Author(s):  
Rajesh S. Shinde ◽  
Ninad Katdare ◽  
Naveena A. N. Kumar ◽  
Rahul Bhamre ◽  
Ashwin Desouza ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Neoadjuvant Chemoradiation ◽  
Histological Subtype

Cetuximab in combination with chemoradiotherapy prior to surgery in patients with resectable, locally advanced esophageal carcinoma: A prospective, multicenter phase lb-ll trial of the Swiss Group for Clinical Cancer Research (SAKK 75/06)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4570-4570
Author(s):  
T. Ruhstaller ◽  
M. Pless ◽  
J. C. Schuller ◽  
H. Kranzbühler ◽  
R. von Moos ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase Ii ◽  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Thoracic Esophagus ◽  
Clinical Cancer Research ◽  
Intention To Treat ◽  
Grade 3

4570 Background: Cetuximab significantly enhances efficacy of radiotherapy and chemotherapy in head and neck cancer. We investigated the safety and feasibility of adding cetuximab to neoadjuvant chemoradiation of locally advanced esophageal cancer. Methods: Pts with resectable, locally advanced squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (staged by EUS, CT and PET scan) were treated with 2 cycles of induction chemotherapy (docetaxel 75mg/m2, cisplatin 75mg/m2 q3w and weekly cetuximab 250mg/m2), followed by concomitant chemo- immuno-radiation therapy (CIRT: docetaxel 20mg/m2, cisplatin 25mg/m2 and cetuximab 250mg/m2 weekly five times concomitant with 45 Gy radiotherapy in 25 fractions); followed by surgery 4–8 weeks later. The phase I part consisted of 2 cohorts of 7 patients each, without and with docetaxel during CIRT, respectively. Interpatient dose-escalation (adding docetaxel during CIRT) was possible if < 2 out of 7 pts of the 1st cohort experienced limiting toxicity. Having finished the phase 1 part, 13 additional patients were treated with docetaxel-containing CIRT in a phase II part. Pathological response was evaluated according to the Mandard classification. Results: 27 pts from 12 institutions were included. As of today, results from 20 pts are available (cohort 1: 7, cohort 2: 7, phase ll : 6). Median age was 64yrs (range 47–71). 11 AC; 9 SCC. 19 pts (95%) completed CIRT (1 pt stopped treatment during induction therapy due to sepsis). 17 pts underwent resection (no surgery: 1pt for PD, 1pt for cardiac reasons). Grade 3 toxicities during CIRT included anorexia 15%, dysphagia/esophagitis 15%, fatigue 10%, nausea 10%, pruritus 5%, dehydration 5%, nail changes 5% and rash 5% .1 pt suffered from pulmonary embolism. 13 pts (65%, intention-to-treat) showed a complete or near complete pathological remission (cohort 1: 5, cohort 2: 4, phase II: 4). Conclusions: Adding cetuximab to preoperative chemoradiation for esophageal cancer is safe and feasible in a community-based multicenter setting. Antineoplastic activity is encouraging with 65% pathological responders. [Table: see text]

The influence of seminal events on the transition from adjuvant to neoadjuvant chemoradiation in the treatment of locally advanced rectal adenocarcinoma (LARC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 631-631
Author(s):  
Jeremy Warner ◽  
Rebecca A. Miksad ◽  
Deborah Nagle ◽  
Robert Najarian ◽  
Michael Goldstein
Keyword(s):  
Meta Analysis ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Neoadjuvant Chemoradiation ◽  
Phase Iii ◽  
Definitive Treatment ◽  
Current Standard ◽  
Pivotal Phase ◽  
The Impact

631 Background: Factors leading to uptake of new oncology treatment innovations are poorly understood. In particular, the degree to which seminal events, such as report of pivotal phase III trials, influence practice is unclear. For example, preoperative (pre-op) 5-fluorouracil + radiation (5-FU + RT) is the current standard of care for definitive treatment of LARC. However, postoperative (post-op) 5-FU + RT was standard before the seminal German Rectal Cancer Study Group (GRCSG) results were published. We investigated the impact of seminal events on the change in practice pattern from pre- to post-op 5-FU + RT at our institution. Methods: Patients with LARC (T2N+; any T3; any T4) treated at our institution between 1994-2010 were identified from the cancer registry. The date of diagnosis was compared to the dates of three seminal events: A) JAMA meta-analysis publication; B) publication of GRCSG results; C) founding of a multidisciplinary clinic at our institution. Pearson Chi square was used for univariate analysis. Results: 334 patients were evaluable. RT +/- 5-FU was delivered pre-op for 207 patients, post-op for 127 patients. The unadjusted odds ratio (OR) for receiving pre-op treatment after vs. before each seminal event was similar: (A) 4.16; (B) 4.08; (C) 3.91. When patients diagnosed prior to (A) or after (C) were excluded, (B) appeared to have a smaller effect, OR 2.07 (p = .053) (Table). Conclusions: All seminal events had similar associated OR, indicating that the process of uptake of the innovation of pre-op 5-FU + RT was gradual. The seminal GRCSG publication, when temporally isolated, had only modest effect. This suggests that report of seminal results is necessary but not sufficient for uptake of a new therapy innovation in LARC at our institution. Whether this pattern of uptake is generalizable is worthy of further investigation. [Table: see text]

Positron emission tomography-computed tomography (PET-CT) for the assessment of pathologic response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 537-537
Author(s):  
Noman Ashraf ◽  
Saqib Razzaque ◽  
Ben C. Creelan ◽  
Julio C. Chavez ◽  
David Shibata ◽  
...  
Keyword(s):  
Overall Survival ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Rectal Adenocarcinoma ◽  
Neoadjuvant Chemoradiotherapy ◽  
Standardized Uptake Value ◽  
Neoadjuvant Chemoradiation ◽  
Significant Trend ◽  
Pet Ct

537 Background: Preoperative 5-fluorouracil and radiation (FU-XRT) has been demonstrated to improve recurrence-free survival in locally advanced rectal adenocarcinoma, however the role of interval PET-CT remains unclear. We performed a retrospective study with the primary objective of examining the association of change in standardized uptake value (SUV) by PET-CT after neoadjuvant chemoradiation and pathologic complete response (path CR) to survival. Methods: Data was extracted for cases at our institution between August 2006–August 2009, with last follow-up performed July 2012. Patients were included if (i) they had completed a full course of preoperative FU-XRT, followed by surgery with intent for R0 resection, and (ii) pre- and post- therapy PET-CT as well as pathologic reports were available for review. Data was compared by Fischer's exact and Wilcoxon rank-sum, and survival was analyzed using Kaplan-Meier method. Clinicopathologic data was compared by log-rank test and univariate Cox proportional hazards for relationship to overall survival (OS). Results: Of 128 total rectal cancer cases reviewed, 25 (19%) met inclusion criteria. Characteristics of 25 patients included: 13 female, age 57± 14 years (median ± SD). After 116 patient-years of follow-up, median OS was not reached; mean OS was 4.6 ± 0.9 years. Mean baseline pre-treatment PET SUV (18.5 ± 9.1) decreased after neoadjuvant FU-XRT (5.0 ± 4.3, p < 0.0001). Five achieved path CR. Presence of earlier stage was associated with non-significant trend towards improved chance of pathologic CR (RR 3.1, p = 0.07). A decrease in PET SUV by 80% or more was associated with improved odds of path CR (OR 25, 95% CI 1.2 - 513, p = 0.009), and was also associated with a non-significant trend towards improved OS (HR 0.19, 95% CI 0.01 - 2.7). Path CR was associated with a non-statistically significant trend to improved overall survival (HR 0.28, 95% CI 0.01 - 8.4). Conclusions: Reduction in PET-CT SUV after neoadjuvant chemoradiation may be a useful predictor of pathologic CR in rectal adenocarcinoma. These exploratory findings need to be validated in larger prospective studies.

Phase 2 study of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with metastatic cutaneous squamous cell carcinoma (mCSCC; Group 1): 12-month follow-up.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9526-9526 ◽  
Author(s):  
Alexander David Guminski ◽  
Annette May Ling Lim ◽  
Nikhil I. Khushalani ◽  
Chrysalyne D. Schmults ◽  
Leonel Fernando Hernandez-Aya ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Adverse Events ◽  
Median Duration ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase 2 ◽  
Primary Analysis ◽  
Phase 2 Study ◽  
Grade 3

9526 Background: Primary analysis (Oct 2017) of cemiplimab (REGN2810) in pts with mCSCC in a Phase 2 study demonstrated substantial antitumor activity, durable responses, and acceptable safety profile. We now report 12-month follow-up data from these pts (NCT02760498; data cutoff date: Sep 20, 2018). Methods: Pts with mCSCC received cemiplimab 3 mg/kg IV every 2 weeks (Q2W). Tumor measurements were performed Q8W. The primary objective was to evaluate objective response rate (ORR; complete response [CR] + partial response [PR]) according to independent central review (per RECIST 1.1 for scans; modified WHO criteria for photos). Results: 59 pts (median age: 71 years) were enrolled. Median duration of follow-up was 16.5 months (range: 1.1–26.6). ORR by central review was 49.2% (95% CI: 35.9–62.5; 10 CRs and 19 PRs [4 CRs and 25 PRs by investigator-assessment (INV)]). Median duration of response (DOR) has not been reached. The longest DOR at data cut-off was 21.6 months and was still ongoing. Observed DOR exceeded 12 months in 22/29 pts (75.9%) with response. Durable disease control rate (stable disease or response for ≥16 weeks) was 62.7% (95% CI: 49.1–75.0). Median observed time to response was 1.9 months (range: 1.7–9.1). Median progression-free survival was 18.4 months (95% CI: 7.3–not evaluable); median overall survival has not been reached. The most common treatment-emergent adverse events (all grades, Grade ≥3) were diarrhea (28.8%, 1.7%), fatigue (25.4%, 1.7%), and nausea (23.7%, 0%). By INV, grade ≥3 immune-related adverse events occurred in 13.6% of pts. Conclusions: This analysis demonstrates substantial antitumor activity and increasing DOR with cemiplimab 3 mg/kg Q2W in pts with mCSCC. There were no new safety signals. These data strongly support the recent FDA approval of cemiplimab-rwlc for pts with mCSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Clinical trial information: NCT02760498.

scholarly journals Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Raquel Conde-Muíño ◽  
Marta Cuadros ◽  
Natalia Zambudio ◽  
Inmaculada Segura-Jiménez ◽  
Carlos Cano ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Rectal Adenocarcinoma ◽  
Surgical Techniques ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
High Local Recurrence Rate

There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile’s ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

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