Imatinib mesylate therapy in advanced gastrointestinal stromal tumors—A Regional cancer centre experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 19505-19505
Author(s):  
K. M. Patel ◽  
P. M. Shah ◽  
S. N. Shukla ◽  
B. J. Parikh ◽  
A. S. Anand ◽  
...  

19505 Background: The treatment of gastrointestinal stromal tumors has been revolutionised by the advent of Imatinib, a specific tyrosine kinase inhibitor. Post operative local and metastatic recurrences of this tumor have been effectively managed by Imatinib. Here we present our experience of Imatinib in recurrent locally advanced/metastatic gastrointestinal stromal tumors (GIST). Methods: From Nov 2001 to Sep 2005, 33 patients with metastatic and / or locally advanced inoperable CD-117 positive GIST were offered imatinib mesylate therapy at 400 mg/day p.o. A total of 21 patients were evaluable for tumor response. Follow up period ranged from 4 months to 38 months with median follow up period being 18 months. Median age is 58 yrs, M:F ratio is 6:4. ECOG performance status was 0–1 in 70% (23 patients) and 2 in 30% (10 patients). 70% patients had post surgery recurrence. 2 patients (6%) had received adjuvant chemotherapy prior to recurrence. 30% (10 patients) had local recurrence, 40% (13 patients) had metastatic disease while 30% (10 patients) had local recurrence as well as metastatic disease. Results: Response evaluation was done by RECIST criteria. 15% (5 patient) showed CR while PR rates were 30% (10 patients). The overall major response (CR+PR) was 45%. The overall progression free survival was as high as 80%. All the patients who had a progression free survival also had a significant improvement in quality of life. Conclusions: Imatinib mesylate therapy shows significant survival benefits in locally advanced inoperable/metatstatic gastrointestinal stromal tumors. It will be a very long time before PET scan for evaluation and follow up becomes feasible in developing country setting. No significant financial relationships to disclose.

2021 ◽  
Author(s):  
Weihao Li ◽  
Jianhong Peng ◽  
Xinyue Li ◽  
Rongxin Zhang ◽  
Binyi Xiao ◽  
...  

Abstract Background The role of surgery in patients with metastatic, recurrent or unresectable locally advanced gastrointestinal stromal tumors (GIST) who respond to imatinib mesylate (IM) treatment is still not formally defined. Therefore, we systemically searched and analyzed the available literature to evaluate the oncologic benefits of surgery in this specific population. Methods A systematic literature search of the PubMed, Embase, and Cochrane Library databases was performed to identify relevant articles on July 16, 2020. Pooled data analysis was also performed using Review Manager. Results Totally 10 studies including 1188 patients (410 patients in the surgery group and 778 patients in the no surgery group) were included in the final analysis. No significant differences in baseline clinical characteristics were found except that patients in the surgery group were significantly younger (WMD, -5.02, 95% CI, -8.38 to -1.67, P = 0.003). In the overall population, pooled data showed a significant improvement in overall survival (OS) (HR, 0.62; 95% CI, 0.53 to 0.73; P < 0.0001) and progression-free survival (PFS) (HR, 0.57; 95% CI, 0.44 to 0.72; P < 0.0001) with surgery. In the subgroup analysis, the impact of surgery on patient response to IM treatment was further confirmed (OS: HR, 0.67; 95% CI, 0.55 to 0.81; P < 0.0001; PFS: HR, 0.62; 95% CI, 0.46 to 0.82; P = 0.009). Conclusions Surgery prolongs the OS and PFS of patients with metastatic, recurrent, or unresectable locally advanced GIST who respond to IM treatment. Future prospective, multicenter RCTs are warranted.


Cancer ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 2237-2244 ◽  
Author(s):  
Lucian R. Chirieac ◽  
Jonathan C. Trent ◽  
Dejka M. Steinert ◽  
Haesun Choi ◽  
Ying Yang ◽  
...  

2008 ◽  
Vol 26 (4) ◽  
pp. 626-632 ◽  
Author(s):  
Charles D. Blanke ◽  
Cathryn Rankin ◽  
George D. Demetri ◽  
Christopher W. Ryan ◽  
Margaret von Mehren ◽  
...  

PurposeTo assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors (GIST) at a standard dose (400 mg daily) versus a high dose (400 mg twice daily).Patients and MethodsPatients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial. At registration, patients were randomly assigned to either standard or high-dose imatinib, with close interval follow-up. If objective progression occurred by Response Evaluation Criteria in Solid Tumors, patients on the standard-dose arm could reregister to the trial and receive the high-dose imatinib regimen.ResultsSeven hundred forty-six patients with advanced GIST from 148 centers across the United States and Canada were enrolled onto this trial in 9 months. With a median follow-up of 4.5 years, median progression-free survival was 18 months for patients on the standard-dose arm, and 20 months for those receiving high-dose imatinib. Median overall survival was 55 and 51 months, respectively. There were no statistically significant differences in objective response rates, progression-free survival, or overall survival. After progression on standard-dose imatinib, 33% of patients who crossed over to the high-dose imatinib regimen achieved either an objective response or stable disease. There were more grade 3, 4, and 5 toxicities noted on the high-dose imatinib arm.ConclusionThis trial confirms the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST but did not show any advantage to higher dose treatment. It appears reasonable to initiate therapy with 400 mg daily and to consider dose escalation on progression of disease.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 224-224
Author(s):  
Abdel Karim Dip Borunda ◽  
Alejandro J. Silva

224 Background: Stromal tumors of the digestive tract are uncommon malignant diseases, and are subclassified as leiomyosarcomas and gastrointestinal stromal tumors (GIST) depending on the molecular expression of CD117 (KIT). GISTs represent 1% of malignant tumors affecting this anatomical site. Located diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since Tyrosine – kinase inhibitors were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods: We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results: We obtained information of 71 patients with metastatic, nonresectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%), with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%) most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 23.6m and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400mg per day. Treatment was well tolerated in most cases. Conclusions: Metastatic GIST evaluated in our center shows a different affection in gender and age, our population shows a different response to TKI’s, than reported in other series with superior overall survival, Poor prognosis is associated with lung affection. Biological studies will be started for the molecular evaluation of these tumors.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17008-e17008
Author(s):  
Maria Luisa Romero ◽  
Jose Luis Gonzalez Vela ◽  
David Hernandez Barajas ◽  
Ascary Velazquez-Pacheco ◽  
Abrham Josafath Hernández ◽  
...  

e17008 Background: Mexico is the sixth country with the highest number of diabetics, this being the second cause of death. Between 8-18% of cancer patients have Diabetes (DM) as comorbidity. Studies have reported DM has worst prognosis in Overall Survival (OS) and Progression Free Survival (PFS) in patients with Cervical Cancer (CC). Aim: to compare OS in patients (pt) with a diagnosis of CC and DM, and to evaluate this outcome in relation to the clinical stage and the glycemic level at diagnosis of CC. Methods: data was obtained from pt treated for invasive CC between 2006 and 2016. Pt aged ≥20 years, with squamous, adenocarcinoma or adenosquamous histology. 59 pt with CC and DM in group 1 (G1), and 118 pt with CC without DM in group 2 (G2), paired 1:2 according to clinical stage, age and comorbidities. Results: Prevalence of DM in pt with CC was 16%. Follow-up of 142.2 months (median of 40.4 months), lower OS for G1 was seen (74.6% vs 77.1%), without statistical significance (p.803). PFS was similar for both groups (67.8% G1 vs 66.9% G2, p .608). In patients with locally advanced and metastatic disease, a lower OS and PFS were found in G1, without statistical significance. 42.4% diabetic pt had glycemic level < 130 mg / dL). OS was lower in pt with higher glycemic level (70.6% vs 80%), not being statistically significant (p .32). PFS was similar in both groups (G1: 68% vs G2: 67.6%, p.852). Analysis for influence of metformin treatment, evidenced a higher OS among pt receiving metformin (84.8% vs 61.5%), without statistical significance (p 0.65). PFS was higher in the metformin group (78.8 vs 53.8%), with a trend towards statistical significance (p .052). Conclusions: Pt diagnosed with CC and DM do not have different OS compared to those without DM. There was a tendency towards the improvement of PFS in pt with CC and DM, who received metformin.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS472-TPS472
Author(s):  
Hirva Mamdani ◽  
Rutika Mehta ◽  
Christos Fountzilas ◽  
Milan Radovich ◽  
Susan Perkins ◽  
...  

TPS472 Background: Adenocarcinoma of esophagus (EAC) and GEJ is the fastest rising cancer in the US. The outcomes are extremely poor with median overall survival (OS) being 12 mo in patients (pts) with metastatic disease. The standard first line treatment for metastatic EAC is platinum-based regimen with median progression free survival (PFS) of 6 mo. Second line options are associated with limited efficacy. An analysis of TCGA has shown 40% of EAC harboring abnormalities in HR genes, most likely resulting from chronic acid reflux induced DNA damage. HR dysregulation is commonly associated with high LOH. Sensitivity to PARP inhibition has been shown to be a surrogate for HR defects or BRCAness phenotype. Clinically PARP inhibitors have shown activity in HR defective prostate and ovarian cancers. These findings provide the basis for this study. Methods: Pts with metastatic esophageal/GEJ/proximal gastric adenocarcinoma, previously treated with 1 line of platinum containing chemotherapy, and harboring high LOH and/or deleterious alteration(s) in HR genes ( BRCA1/2, PALB2, ATM, BARD1, BRIP1, CDK12, CHEK2, FANCA, RAD51, RAD51B, RAD51C, RAD51D, RAD54L, NBN, ARID1A, GEN1) are eligible for this study. Pts can be prescreened at the time of diagnosis of locally advanced or metastatic disease by genomic analysis of the most recent available tumor tissue. Pts will receive oral niraparib until disease progression or unacceptable toxicity. Primary objective is response rate (RR). Secondary objectives are safety and tolerability, progression free survival (PFS), and disease control rate (DCR). Exploratory objectives include correlation between high LOH and response to niraparib, mechanisms of resistance to PARP inhibition, EZH2 expression and its correlation with response and resistance to PARP inhibition, and analysis of germline HR gene mutations and correlation with response to niraparib. Estimated sample size is 43. The study has recently opened to accrual at Indiana University with intended collaboration with 2 additional sites. Clinical trial information: NCT03840967.


2019 ◽  
Vol 26 (1) ◽  
pp. 107327481986377 ◽  
Author(s):  
Kien Do Hung ◽  
Quang Le Van ◽  
Gia Nguyen Hoang ◽  
Phuong Nguyen Thi Bich

Only limited data are available concerning the long-term outcomes of imatinib treatment among Vietnamese or Asian patients with unresectable or recurrent gastrointestinal stromal tumors (GISTs). Our study, which was conducted in 188 patients, aimed to assess the efficacy of imatinib mesylate against unresectable or recurrent GISTs. Imatinib had a high response rate and long survival. Some predictors favorable for progression-free survival and overall survival are good performance status and response with imatinib. Findings are discussed in relation to clinical practice in low- and middle-income country.


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