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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e15799-e15799
    Abstract: e15799 Background: Given the benefit noted with epidermal growth factor receptor (EGFR) antibodies in KRAS wild-type colorectal cancer, we conducted a phase II trial to evaluate the efficacy of panitumumab in metastatic small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Methods: This is a single-center open-label single arm two-stage phase II study. The primary objective was response rate (RR). Secondary objectives included overall progression-free survival (PFS), overall survival (OS) and toxicity. Eligibility included: KRAS exon 2 wild-type, ECOG PS 0-1, metastatic disease, adequate organ function and prior progression or intolerance to fluoropyrimidine with oxaliplatin. Panitumumab was administered at a dose of 6mg/kg IV every 14 days. Next generation sequencing panels were used for genomic analysis. Results: 9 patients [M/F 7/2, median age: 61 yrs (range: 40-74), ECOG PS 0/1: 2/7] were enrolled from September 2013 to October 2015. 1 pt had AAC (pancreaticobiliary subtype) and 8 pts had SBA (duodenal in 3, jejunal/ileal in 5). The most common toxicity was grade 1 acneiform rash in all patients. The most common grade 2/3 toxicities were anemia (33%), fatigue (22%), hypomagnesemia (22%) and skin infection (22%). None of the patients had a response, 2 patients had SD while the remaining 7 patients had PD. At a median follow-up time of 16.6 months, the median PFS and median OS were 2.4 months and 5.6 months, respectively. Extended RAS mutational testing identified 0/9 patients with mutations in extended KRAS or NRAS. Further genomic analysis of genes relevant to anti-EGFR activity (BRAF, PIK3CA and ERBB2) identified 2/9 patients with BRAF G469A mutation, 1/9 patients with PIK3CA H1047R mutation, and 0/9 patients with ERRB2 mutations. Conclusions: Although well tolerated, panitumumab had minimal clinical activity in patients with metastatic SBA and AAC. Given recent findings suggesting that right-sided colon cancers (hindgut derivation) benefit less from anti-EGFR therapy compared to left-sided colon cancers (midgut derivation), we propose that our findings may relate to the primarily foregut (proximal duodenum) and midgut (distal duodenum to ileum) derivation of the small bowel. Clinical trial information: NCT01202409.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e15137-e15137
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e15781-e15781
    Abstract: e15781 Background: Recent studies have shown that the pancreatic ductal adenocarcinoma (PDAC)-associated gut microbiome can play a major in modulating responses to therapies. Antibiotics (ATB) can potentially alter the tumor and gut microbiota diversity and composition leading to modified responses to chemotherapeutic/immune therapy regimens and hence the survival. Methods: We retrospectively analyzed the clinical data of 148 patients (pts) with documented metastatic PDAC seen at MD Anderson Cancer (MDACC) from 2009 to 2017. Along with demographic and chemotherapy regimen details the duration, type and reason for antibiotic consumption for more than 3 days were recorded. Overall survival (OS) and Progression free survival (PFS) were calculated. Log-rank test and Gehan-Breslow-Wilcoxon test were used to check the statistical significance for OS and PFS. Confounding variables were also accounted. Results: We analyzed the data of 148 metastatic pancreatic cancer pts[mean age 62.73, 50.67% males 49.32% females, 75.6% white] out of which 135 patients received antibiotics. The infectious sources consisted of intraabdominal (n = 68), urinary (n = 36), respiratory (n = 57), skin/soft tissue infections (n = 26), blood related (n = 24), and others (n = 76). Beta lactams (n = 96) and Quinolones (n = 96) were the most commonly prescribed antibiotics. When comparing outcomes, we found out that the median OS for pts taking macrolides (n = 24) was 541 days compared to 341 days for pts not taking macrolides (n = 144) (HR = 0.6384, p value = 0.0191) . Median PFS for pts taking macrolides was 178 days versus 124 days in those not taking macrolides (HR = 0.6331, p value = 0.0188). The potential confounders were having a respiratory infection or the type of chemotherapy regimen. Conclusions: Macrolide consumption for 〉 3 days leads to a prolonged OS and PFS. Consistent with the preclinical evidence our data suggests a potential role for some antibiotics in modulating PDAC-associated gut microbiome. Hence, having implications on the survival of PDAC pts. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 4_suppl ( 2018-02-01), p. 369-369
    Abstract: 369 Background: Chemotherapy is widely used as a component of treatment of localized pancreatic ductal adenocarcinoma (PDAC). Pre-operative chemotherapy is associated with early treatment of micro-metastases and guaranteed delivery of all components of multimodality therapy. For locally advanced (LA) PDAC, induction chemotherapy is standard of care. We evaluated the use of gemcitabine and nab-paclitaxel (Gem/nab-P) as first-line therapy in localized PDAC. Methods: Records of pts with localized PDAC who initiated Gem/nab-P at a single institution from 2013-2015 were retrospectively reviewed. Clinicopathologic features, dose and outcomes were evaluated. Pts were staged using our previously published criteria: potentially resectable (PR), borderline type A (BR-A) (anatomy amenable to vascular resection), BR-B (biology suspicious for metastatic disease including high CA19-9), BR-C (co-morbidities requiring medical optimization), and LA. Co-morbidities were classified using adult comorbidity evaluation-27 score. Overall survival (OS) was analyzed using Kaplan Meier method. Results:99 pts [M/F: 50/49; median age: 70 yrs (range 30-85); PR/BR/LA: 45/14/40] were treated with Gem/nab-P. Clinical staging showed PR+BR-A/BR-B+C: 20/39. BR-B+C included one or more of the following factors: age ≥80 yrs [13%], ECOG PS ≥2 [13%] , moderate/severe co-morbidities [55%], CA19-9≥1000 [28%] , suspicion for metastatic disease [21%]. Majority of pts received biweekly Gem/nab-P dosing [standard/biweekly/other: 10/80/9] with minimal grade 4 toxicity. 45/99 pts received chemoradiation after Gem/nab-P [30Gy/50.4Gy: 15/30]. 12/20 (60%) PR+BR-A, 2/39 (5%) BR-B+C and 1/40 (3%) LA pts underwent pancreatectomy. 13/15 resected pts received adjuvant chemotherapy. At median follow-up of 26 mo, median OS was 18 (95% CI: 15.6-20.5) mo for all, 17 (95% CI: 14.6-19.5) mo for unresected and not reached for resected pts (p = 0.03). Conclusions: A significant number of pts with resectable PDAC albeit aggressive biology (BR-B) and/or medically inoperable disease (BR-C) received first-line Gem/nab-P; resection rates were lower compared to PR/BR-A pts. Biweekly dosing is being used in localized PDAC and is well tolerated.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 320-320
    Abstract: 320 Background: Pancreatic cancer is a disease that generally presents in advanced stage and is nearly fatal in all cases. In 2011, we reported our experience with pancreatic cancer patients enrolled on phase 1 clinical trials from 2004-2009. At the time, gemcitabine and erlotinib were the only US FDA approved drugs for pancreatic cancer. Median overall survival from presentation in the phase 1 clinic was 5 months. After an additional 5 years of progress, we queried the impact of novel cancer therapeutics, evolving molecular profiling, and targeted therapy on pancreatic cancer patient outcomes in the phase 1 setting. Methods: A retrospective review of advanced pancreatic adenocarcinoma patients from the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center, was conducted for patients treated from 1/2009 to 1/2014. Statistical analyses utilized the Kaplan-Meier method. Results: A total of 90 patients were identified in 50 trials reviewed. Median age was 62 years (40-84), 57% were male, and 40% had stage IV disease at presentation. Median documented PS was 1 (range 0-3). The median time from diagnosis to treatment on a phase I protocol was 15 months (0.2-119). Patients were treated with an average of 4 prior regimens prior to Phase 1 referral (0-10) with 8% having undergone 〉 5 treatments. The median overall survival from the first phase I treatment was 5.2 months, 95% CI = (4.4-6.3) and the 1 year overall survival from the first phase 1 treatment was 15% (9%- 25%). The median duration on regimen with best phase I response was 1.9 months (0.2-21.3). Of 88 evaluable, the best responses were PR in 1 patient and SD ( 〉 6 months) in 5 patients. Although 47 patients had biomarker profiling performed and 61 patients were treated with targeted therapy alone or in combination with cytotoxic therapy, only 6 patients (5 PD, 1 SD currently on protocol) were placed on trials based on biomarker testing results. Conclusions: Pancreatic cancer remains a difficult disease to treat with poor outcome. Referral to phase 1 occurs late in the disease course. Biomarker based therapies may be more successful with more stringent patient selection and when referred earlier or used prior to cytotoxic treatment.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: International Journal of Radiation Oncology*Biology*Physics, Elsevier BV, Vol. 97, No. 2 ( 2017-02), p. 323-332
    Type of Medium: Online Resource
    ISSN: 0360-3016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1500486-7
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  • 7
    In: International Journal of Radiation Oncology*Biology*Physics, Elsevier BV, Vol. 94, No. 4 ( 2016-03), p. 755-765
    Type of Medium: Online Resource
    ISSN: 0360-3016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 1500486-7
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 4018-4018
    Abstract: 4018 Background: BTCs are often diagnosed at an advanced stage and have a poor prognosis. The standard therapy for aBTCs is the combination of GC. However, the median overall survival (mOS) is dismal at 11.7 months (mos) with a median progression free survival (mPFS) of 8 mos. Methods: A single arm, phase II study was conducted at MD Anderson and Mayo Clinic Arizona. Patients (pts) with aBTC were treated at initial dose level of G/C/N (in mg/m 2 ) at 1000/25/125 (n = 27) which was reduced to lower doses due to grade 3/4 hematological (heme) toxicity (tox) - G/C/N: 800/25/100 (n = 33). Cycles were q21 days with restaging q3 cycles until progression. PFS was the primary endpoint (endpt). Using a Bayesian hypothesis test-based design, we assumed mPFS of 8 mos under the null hypothesis (H0), 10 mos under the alternative (H1). Secondary endpts included mOS, RECIST v1.1 response rate (RR), safety and CA19-9 response. Results: 60 pts were enrolled with data on 51 available as of the time of this abstract (age: median 60 yrs [range 31-77], ECOG PS 0/1 (17/34), M/F (30/21), intrahepatic cholangiocarcinoma/extrahepatic/gallbladder (32/8/11). Median follow-up was 11.5 mos and median number of treatment (trmt) cycles = 5. Pts at initial dose level had significant grade 3/4 heme tox: neutropenia, febrile neutropenia, anemia, and thrombocytopenia leading to trmt discontinuation in 6/27 pts. After dose reduction to G/C/N (in mg/m 2 ) at 800/25/100, trmt was better tolerated with only 4 pts experiencing grade 4 heme tox. Non-heme tox were grade 3 in 10 pts: nausea/vomiting, diarrhea, thromboembolic event/CVA, hypokalemia, constipation, cystitis, LFT elevations. In the initial 51 pts, mPFS = 11.4 mos (95% CI: 6.1, not reached) and mOS not reached (estimated 〉 20 mos, 1-year survival rate 66.7%; 95%CI: 65.9-92.2%). 34 pts evaluable for response: disease control rate (PR+CR+SD)-82.3% and RR-32.3%. 3 unresectable cases were operated post trmt with 1 pathologic CR. Conclusions: The combination of GCN was well tolerated at adjusted doses and demonstrates encouraging preliminary efficacy having met its mPFS endpt and a 1-year survival rate higher than historical control. These results merit evaluating GC +/-N in a randomized controlled study. Clinical trial information: NCT02392637.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. e15642-e15642
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e15642-e15642
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 24_Supplement ( 2019-12-15), p. B36-B36
    Abstract: Background: More than half of patients (pts) with pancreatic cancer (PC) initially present with unresectable, locally advanced disease (LAPC). Data on management of these pts after systemic chemotherapy are scarce. Many clinicians utilize a strategy of induction chemotherapy followed by consolidative concurrent chemoradiation (CRT) for pts not progressing on initial chemotherapy. How to manage pts after CRT is controversial. We sought to evaluate the role of maintenance chemotherapy (MCT) after CRT in pts with LAPC. Methods: We retrospectively analyzed LAPC pts treated with CRT at MD Anderson from 2005-2018. Pts who were taken for curative-intent surgery were excluded. Primary and secondary outcomes were median progression-free survival (mPFS) and median overall survival (mOS), respectively, as measured from the start date of CRT. Data were also obtained on pt demographics, response, and duration of induction chemotherapy as well as MCT regimens. Results: We included 165 pts with LAPC treated with CRT in our analysis. Median age was 66 (range 39 – 84), and 97 (59%) pts were male. Median follow-up was 12.9 months. The median duration from initiation of induction chemotherapy to start of CRT was 4.4 months. Most pts (84%) received 1 line of induction chemotherapy prior to CRT. Ten pts (6%) did not receive induction chemotherapy and 17 pts (10%) received at least 2 lines prior to CRT. All but 9 pts (94%) developed disease progression (PD) after CRT, and 49 pts (33%) had PD within 3 months of CRT. On univariate analysis, PD on the induction chemotherapy regimen immediately prior to CRT was associated with shortened PFS (HR 2.46, p & lt; 0.001) and OS (HR 2.96, p & lt; 0.001) after CRT. Most pts (78%) did not receive MCT after CRT. 69% of pts who received MCT were male, compared to 56% of those who did not receive MCT. The percentages of pts who had PD on the chemotherapy regimen immediately prior to CRT in the MCT and no-MCT groups were 9% and 12%, respectively. Sixteen pts who received MCT were treated with either gemcitabine alone or a gemcitabine-containing regimen, while 14 pts received capecitabine monotherapy. On univariate analysis, the use of MCT after CRT was associated with prolonged mPFS (9.0 vs. 4.2 months, p = 0.01), but was not associated with an increase in mOS (15.5 vs. 12.5 months, p = 0.14). On multivariable analysis controlling for race, radiation dose, age, and whether there was progression on the chemotherapy regimen prior to CRT, the use of MCT was significantly associated with both prolonged PFS (HR 0.45, p & lt; 0.001) and OS (HR 0.66, p = 0.047). Conclusions: In this single-institution retrospective analysis of 165 pts with LAPC treated with CRT, treatment with post-CRT MCT was associated with a significant improvement in both PFS and OS as measured from the start date of CRT. Based on these results, MCT may be an appropriate option for pts with LAPC who have not progressed following consolidative CRT, and a prospective trial should be performed to better address this knowledge gap. Citation Format: Jonathan D. Mizrahi, Shalini Moningi, Graciela M. Nogueras-Gonzalez, Robert A. Wolff, Milind M. Javle, Gauri R. Varadhachary, Linus Ho, David R. Fogelman, Kanwal P. Raghav, Michael J. Overman, Christopher H. Crane, Joseph M. Herman, Albert C. Koong, Eugene J. Koay, Jane E. Rogers, Shubham Pant. Maintenance chemotherapy after chemoradiation in patients with locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B36.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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