scholarly journals Pembrolizumab for Microsatellite Instability-High or Mismatch Repair Deficient Small Bowel Adenocarcinoma or Appendiceal Adenocarcinoma

2021 ◽  
Vol 1 (10) ◽  
Author(s):  
Keeley Farrell ◽  
Jennifer Horton
Keyword(s):  
Small Bowel ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Progression Free Survival ◽  
Clinical Effectiveness ◽  
Complete Response ◽  
Small Bowel Adenocarcinoma ◽  
Appendiceal Adenocarcinoma ◽  
The Cost ◽  
Evidence Based Guidelines

Some adult patients with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) small bowel adenocarcinoma might benefit from pembrolizumab in controlling the disease (i.e., some patients achieved a partial or complete response after treatment). These findings are based on 2 single-arm studies (i.e., no comparator) with fewer than 20 patients in each study, which limits the certainty of the findings. The longer-term benefit of pembrolizumab is unclear, as some outcomes (e.g., progression-free survival, overall survival) were not reached at the time of data analysis. The safety of pembrolizumab in patients with MSI-H/dMMR small bowel adenocarcinoma is unknown (no evidence was found for this population). No evidence was identified regarding the clinical effectiveness of pembrolizumab monotherapy for patients with MSI-H/dMMR appendiceal adenocarcinoma. No evidence was identified regarding the cost-effectiveness of pembrolizumab monotherapy for patients with MSI-H/dMMR small bowel adenocarcinoma or appendiceal adenocarcinoma. No evidence-based guidelines were identified regarding pembrolizumab monotherapy for patients with MSI-H/dMMR appendiceal adenocarcinoma. One guideline was identified that recommends pembrolizumab as an option for initial or subsequent therapy in patients with advanced or metastatic MSI-H/dMMR small bowel adenocarcinoma.

scholarly journals Anti-EGFR Therapy in Metastatic Small Bowel Adenocarcinoma: Myth or Reality?

2020 ◽  
Vol 14 ◽  
pp. 117955492094669 ◽  
Author(s):  
Emanuela Dell’Aquila ◽  
Tea Zeppola ◽  
Marco Stellato ◽  
Francesco Pantano ◽  
Mario Scartozzi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Small Bowel ◽  
Retrospective Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Egfr Inhibitors ◽  
Small Bowel Adenocarcinoma ◽  
Multicenter Observational Study ◽  
Therapeutic Decisions

Background: Due to the relative rarity of small bowel adenocarcinoma (SBA), prospective trials, helping to guide therapeutic decisions, are lacking and the optimal therapy for advanced SBA is unknown. The role of targeted agents, such as anti–epidermal growth factor receptor (EGFR) and anti–vascular endothelial growth factor (VEGF), is unknown. Patients and Methods: This is a retrospective multicenter observational study that included patients with metastatic SBA treated with anti-EGFR antibodies (cetuximab or panitumumab) ± chemotherapy in the first (I) or second (II) line. Results: Thirteen patients with metastatic SBA, recruited from 5 Italian referral institutions, were included in the present retrospective analysis. All patients received anti-EGFR inhibitors as a single agent or in association with chemotherapy. More common G2 treatment–related side effects were skin reaction (8 patients, 53.8%), hypomagnesemia (6 patients, 46.2%), and diarrhea (8 patients, 61.5%). Grade 3 diarrhea was observed in only 1 patient. Conjunctivitis was not reported in any patients. Grade 4 toxicity was not reported. In the overall population, median progression-free survival was 5.526 months (95% confidence interval [CI]: 3.684-12.467). Median overall survival was 15.86 months (95% CI: 14.43-24.30). Complete response was observed in 15% of patients, partial response in 39% of patients, stable disease in 23% of patients, and progression disease in 15% of patients. Conclusions: In this retrospective analysis, anti-EGFR inhibitors showed to be a suitable addendum to chemotherapy in the I and II line, with an excellent tolerance and safety profile both in I and II line.

The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease

2004 ◽  
Vol 199 (3) ◽  
pp. 86
Author(s):  
D.Dean Potter ◽  
Joseph Murray ◽  
John Donohue ◽  
Lawrence Burgart ◽  
David Nagorney ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Small Bowel ◽  
Mismatch Repair ◽  
Small Bowel Adenocarcinoma ◽  
Defective Mismatch Repair

scholarly journals Characterization and Clinical Outcomes of DNA Mismatch Repair Deficient (MMR-D) Small Bowel Adenocarcinoma

2020 ◽  
pp. clincanres.2892.2020
Author(s):  
Alicia Latham ◽  
Jinru Shia ◽  
Zalak Patel ◽  
Diane L Reidy-Lagunes ◽  
Neil H Segal ◽  
...  
Keyword(s):  
Small Bowel ◽  
Mismatch Repair ◽  
Clinical Outcomes ◽  
Dna Mismatch Repair ◽  
Small Bowel Adenocarcinoma ◽  
Dna Mismatch

scholarly journals Bevacizumab in metastatic small-bowel adenocarcinoma: A systematic review and meta-analysis

Rare Tumors ◽  
2019 ◽  
Vol 11 ◽  
pp. 203636131882541 ◽  
Author(s):  
John Paulo Vergara ◽  
Danielle Benedict Leoncio Sacdalan ◽  
Madelaine Amurao-Amante ◽  
Dennis Lee Sacdalan
Keyword(s):  
Systematic Review ◽  
Small Bowel ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Bowel Adenocarcinoma ◽  
Gastrointestinal Malignancies ◽  
Histologic Subtype ◽  
Vascular Epithelial Growth Factor ◽  
American Society

Cancers of the small bowel could account for less than 5% of all gastrointestinal malignancies. Of these tumors, adenocarcinomas were the major histologic subtype and generally carried a poor prognosis. High expression of vascular epithelial growth factor (VEGF) could be seen in small bowel adenocarcinomas. A systematic review was conducted here to determine if bevacizumab, a recombinant humanized antibody against VEGF, could offer clinical benefit among patients with metastatic small bowel adenocarcinoma when combined with chemotherapy. A search for relevant published and unpublished studies was performed using PubMed, ScienceDirect, Google Scholar, the American Society of Clinical Oncology meetings library, ClinicalTrials.gov, and ISRCTN registry. Information on study design, methods, intervention, and outcomes were extracted from selected eligible studies. Methodological quality was then assessed using the Newcastle-Ottawa Scale. There was a significant improvement in mean overall survival with the addition of bevacizumab with chemotherapy versus chemotherapy alone. The use of bevacizumab with chemotherapy, likewise improved progression-free survival and objective response rate compared to chemotherapy alone. Continued use of bevacizumab beyond first progression also appeared to show benefit. The conduct of prospective controlled studies by consortia to offset the rarity of small bowel adenocarcinomas could further elucidate the efficacy of bevacizumab in the treatment of this disease.

scholarly journals Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability

2020 ◽  
Vol 33 (7) ◽  
pp. 1453-1453
Author(s):  
Paolo Giuffrida ◽  
Giovanni Arpa ◽  
Federica Grillo ◽  
Catherine Klersy ◽  
Gianluca Sampietro ◽  
...  
Keyword(s):  
Small Bowel ◽  
Microsatellite Instability ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Bowel Adenocarcinoma ◽  
Infiltrating Lymphocytes

Retrospective analysis of first-line chemotherapy in 132 patients with advanced small-bowel adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 260-260
Author(s):  
T. Tsushima ◽  
N. Boku ◽  
Y. Honma ◽  
H. Takahashi ◽  
S. Ueda ◽  
...  
Keyword(s):  
Small Bowel ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Ampullary Carcinoma ◽  
Small Bowel Adenocarcinoma ◽  
Kaplan Meier ◽  
Group A ◽  
Group B ◽  
Ecog Ps

260 Background: No standard care has been established for advanced small-bowel adenocarcinoma (SBA). The aim of this study is to explore a most promising chemotherapy regimen for advanced SBA. Methods: All data were collected from medical records of patients with advanced or recurrent SBA who received chemotherapy between April 1999 and March 2009 at 41 hospitals in Japan. Selection criteria were as follows: 1) histologically proven SBA, excluding ampullary carcinoma, 2) no previous chemotherapy or radiotherapy, 3) ECOG PS 0-2, 4) adequate bone marrow, hepatic and renal functions, 5) no concomitant malignancy. Patients were divided into the five groups by regimens: group A, fluoropyrimidine alone; group B, fluoropyrimidine + cisplatin; group C, fluoropyrimidine + oxaliplatin; group D, fluoropyrimidine + irinotecan; group E, others. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Results: Demographics of selected 132 patients were: median age (range), 59 (23-78) years; male/female, 87/45; location of primary tumor, duodenum/jejunum/ileum/unknown, 80/32/17/3; advanced/recurrent disease, 91/41. The numbers of the patients in group A, B, C, D and E were 60, 17, 22, 11 and 22, and objective response rates (ORR) in the patients with target lesions were 20% (9/46), 38% (5/13), 42% (8/19), 25% (2/8), 21% (4/19), respectively. Median PFS and OS were 6.0 and 14.0 months for the whole population, and those in each group are shown in the Table.In comparison with fluoropyrimidine alone (A), oxaliplatin-combined regimens (C) associated with better PFS (HR=0.53 [0.31-0.93], p=0.03) and OS (HR=0.64 [0.33-1.25], p=0.19), while cisplatin-combined regimens (B) did not (HR=1.54 [0.88-2.68], p=0.13 for PFS and HR=1.67 [0.94-2.97], p=0.08 for OS) by univariate analysis. Conclusions: It is suggested that oxaliplatin-combined regimens might be the most promising regimen for advanced SBA. [Table: see text] No significant financial relationships to disclose.

A phase II study of 5-FU/l-LV/oxaliplatin (mFOLFOX6) in patients with metastatic or unresectable small bowel adenocarcinoma: A post hoc analysis.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 430-430
Author(s):  
Taro Funakoshi ◽  
Takahiro Horimatsu ◽  
Norisuke Nakayama ◽  
Toshikazu Moriwaki ◽  
Yoshinori Hirashima ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Small Bowel ◽  
Primary Tumor ◽  
Performance Status ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Primary Site ◽  
Small Bowel Adenocarcinoma ◽  
Serum Cea ◽  
Post Hoc

430 Background: Small bowel adenocarcinoma (SBA) is a rare disease. Previous studies suggested several prognostic factors of unresectable SBA, including age, performance status (PS), primary site, resection of primary tumor, histology, and tumor marker (CEA and CA19–9) levels. However, prognostic factors of the patients treated with oxaliplatin–fluoropyrimidine combination therapy were unknown, while these drugs were reported as a promising chemotherapy regimen for SBA. Methods: Previously untreated SBA patients were treated with an mFOLFOX6 regimen, and a post hoc analyses for prognostic factors were performed. Results: Between April 2010 and November 2012, 24 patients were included in this study. The overall response rate was 45% (9/20). The median progression-free survival and overall survival (OS) were 5.4 months (95% CI, 4.8–6.0) and 17.3 months (95% CI, 11.7–19.0), respectively. Univariate analysis revealed that lower PS (HR= 0.27; 95% CI, 0.10–0.77; p= 0.014), primary disease of the jejunum (HR= 0.35; 95% CI, 0.11–1.12; p=0.077), and serum CEA in the normal range (HR= 0.40; 95% CI, 0.14–1.11; p= 0.079) were potential prognostic factors of longer OS (threshold, p< 0.10). Although resection of the primary tumor was not a predictive factor of survival in this study, 54% and 21% of the patients needed surgery (primary resection or bypass) because of stenosis before and during chemotherapy, respectively. It is considered that bowel obstruction should be addressed before and during treatment. Conclusions: PS, primary site, and serum CEA levels are potential prognostic factors of unresectable SBA. There is a higher incidence of bowel stenosis or obstruction caused by the primary tumor before and during the treatment of SBA.

scholarly journals Medication Administration With Inhalers or Nebulizers

2021 ◽  
Vol 1 (11) ◽  
Author(s):  
Khai Than ◽  
Aleksandra Grobelna
Keyword(s):  
Clinical Effectiveness ◽  
Medication Administration ◽  
Chronic Obstructive ◽  
Dry Powder Inhalers ◽  
Metered Dose Inhalers ◽  
Dry Powder ◽  
Obstructive Pulmonary Disease ◽  
Metered Dose ◽  
The Cost ◽  
Evidence Based Guidelines

Delivery of medication via metered-dose inhalers to children or adults with asthma, or adults with chronic obstructive pulmonary disease at emergency departments or intensive care units, may be as effective as nebulizers in terms of clinical parameters and health care resource use. Limited data on adverse events showed no significant differences between metered-dose inhalers and nebulizers. No evidence was found on the clinical effectiveness of dry powder inhalers in comparison with nebulizers or metered-dose inhalers. No evidence was found on the cost-effectiveness of medication administration via metered-dose inhalers, nebulizers, or dry powder inhalers in comparison with each other. No evidence-based guidelines with recommendations regarding the comparative use of metered-dose inhalers, dry powder inhalers, or nebulizers for administration of medication were identified.

Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer

2019 ◽  
Vol 37 (30) ◽  
pp. 2786-2794 ◽  
Author(s):  
Panagiotis A. Konstantinopoulos ◽  
Weixiu Luo ◽  
Joyce F. Liu ◽  
Doga C. Gulhan ◽  
Carolyn Krasner ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Immune Checkpoint Blockade ◽  
Mmr Proteins

PURPOSE Despite the tissue-agnostic approval of pembrolizumab in mismatch repair deficient (MMRD) solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in mismatch repair–proficient (MMRP) and –deficient endometrial cancer (EC). METHODS This phase II study evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: (1) MMRD/ POLE (polymerase ε) cohort, as defined by immunohistochemical (IHC) loss of expression of one or more mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE; and (2) MMRP cohort with normal IHC expression of all MMR proteins. Coprimary end points were objective response (OR) and progression-free survival at 6 months (PFS6). Avelumab 10 mg/kg intravenously was administered every 2 weeks until progression or unacceptable toxicity. RESULTS Thirty-three patients were enrolled. No patient with POLE-mutated tumor was enrolled in the MMRD cohort, and all MMRP tumors were not POLE-mutated. The MMRP cohort was closed at the first stage because of futility: Only one of 16 patients exhibited both OR and PFS6 responses. The MMRD cohort met the predefined primary end point of four ORs after accrual of only 17 patients; of 15 patients who initiated avelumab, four exhibited OR (one complete response, three partial responses; OR rate, 26.7%; 95% CI, 7.8% to 55.1%) and six (including all four ORs) PFS6 responses (PFS6, 40.0%; 95% CI, 16.3% to 66.7%), four of which are ongoing as of data cutoff date. Responses were observed in the absence of PD-L1 expression. IHC captured all cases of MMRD subsequently determined by polymerase chain reaction or genomically via targeted sequencing. CONCLUSION Avelumab exhibited promising activity in MMRD EC regardless of PD-L1 status. IHC for MMR assessment is a useful tool for patient selection. The activity of avelumab in MMRP/non- POLE–mutated ECs was low.

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