Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial

Hess, Viviane; Pratsch, S.; Potthast, Silke; Lee, L.; Winterhalder, Ralph; Widmer, Lukas A.; Cescato, Corinne; Lohri, Andreas; Jost, L.; Stillhart, P.; Paulweber, Bernhard; Herrmann, Richard

doi:10.1093/annonc/mdq242

Cited by 23 publications

(8 citation statements)

References 14 publications

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“…29 In contrast, recent data from prospective clinical trials have provided valid evidence for an intensification of combination chemotherapy in order to improve survival outcome (eg, by use of the FOLFIRINOX regimen). 3031 Thus, novel treatment strategies are urgently awaited and future preclinical and clinical research efforts should focus, for example, on the targeting of different pathways as well as on the improvement of translational research in order to identify and validate relevant targets and molecular pathways in PC. 3233 In contrast to the (preliminary) biomarker results of the PA.3 study, a higher rate of KRAS wild-type patients within our study cohort was observed (30% vs 21%), and the KRAS wild type status was associated with an improved OS in our patient population (of which FFPE tissue was available).…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104)

Heinemann

Vehling-Kaiser

Waldschmidt

et al. 2012

Gut

108

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Objective AIO-PK0104 investigated two treatment strategies in advanced pancreatic cancer (PC): a reference sequence of gemcitabine/erlotinib followed by 2nd-line capecitabine was compared with a reverse experimental sequence of capecitabine/erlotinib followed by gemcitabine. Methods 281 patients with PC were randomly assigned to 1st-line treatment with either gemcitabine plus erlotinib or capecitabine plus erlotinib. In case of treatment failure (eg, disease progression or toxicity), patients were allocated to 2nd-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was time to treatment failure (TTF) after 1st-and 2nd-line therapy (TTF2; non-inferiority design). KRAS exon 2 mutations were analysed in archival tumour tissue from 173 of the randomised patients. Results Of the 274 eligible patients, 43 had locally advanced and 231 had metastatic disease; 140 (51%) received 2nd-line chemotherapy. Median TTF2 was estimated with 4.2 months in both arms; median overall survival was 6.2 months with gemcitabine/erlotinib followed by capecitabine and 6.9 months with capecitabine/erlotinib followed by gemcitabine, respectively (HR 1.02, p¼0.90). TTF for 1st-line therapy (TTF1) was significantly prolonged with gemcitabine/ erlotinib compared to capecitabine/erlotinib (3.2 vs 2.2 months; HR 0.69, p¼0.0034). Skin rash was associated with both TTF2 (rash grade 0/1/2e4:2.9/4.3/ 6.7 months, p<0.0001) and survival (3.4/7.0/ 9.6 months, p<0.0001). Each arm showed a safe and manageable toxicity profile during 1st-and 2nd-line therapy. A KRAS wild-type status (52/173 patients, 30%) was associated with an improved overall survival (HR 1.68, p¼0.005). Conclusion Both treatment strategies are feasible and demonstrated comparable efficacy; KRAS may serve as biomarker in patients with advanced PC treated with erlotinib.

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Section: Discussionmentioning

confidence: 99%

Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104)

Heinemann

Vehling-Kaiser

Waldschmidt

et al. 2012

Gut

108

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“…A Phase I and II clinical study involving patients with an advanced PC being treated with a combination of Capecitabine and Gemcitabine was regarded as a part of our study. Administering a combined therapy between Gemcitabine, oxaliplatin, and Capecitabine for advanced PC gave us results of 4.3‐month median PFS, 7.8‐month median OS of patients, and 8.9‐month median OS in patients signifying good performance; as first‐line treatment of inoperable or metastatic PC with Gemcitabine and Capecitabine, it presented with a median OS of 8 months (Hess et al, ; Scheithauer et al, ; Schilsky, Bertucci, Vogelzang, Kindler, & Ratain, ; Stathopoulos et al, ). The foundation of the combination of 5‐FU with CI and Gemcitabine is to prolong thymidylate synthetase inhibition, thereby increasing the chance of pharmacodynamic with Gemcitabine and reducing the toxicity compared to 5‐FU bolus (Di Costanzo et al, ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of different chemotherapy regimens in treatment of advanced or metastatic pancreatic cancer: A network meta‐analysis

Zhang

Liu

et al. 2017

Journal Cellular Physiology

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We performed a network meta-analysis (NMA) to compare the short- and long-term efficacy of Gemcitabine, Gemcitabine + S-1 (tegafur), Gemcitabine + nab-paclitaxel, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, FOLFIRINOX (oxaliplatin + irinotecan + fluorouracil + leucovorin), Gemcitabine + oxaliplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, Gemcitabine + pemetrexed, Gemcitabine + 5-FU, and S-1 in treating advanced or metastatic pancreatic cancer (PC). The odds radios (OR) or weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRA) were evaluated by a combination of direct evidence and indirect evidence. In total twenty studies were included in this paper. For short-term efficacy, the overall response rate (ORR) was lower for patients treated with Gemcitabine compared with Gemcitabine + S-1, Gemcitabine + Cisplatin, Gemcitabine + irinotecan and S-1. The ORR for FOLFIRINOX was higher compared with Gemcitabine, Gemcitabine + Capecitabine and Gemcitabine + Cisplatin. The disease control rate (DCR) for Gemcitabine was lower compared with Gemcitabine + S-1, Gemcitabine + Cisplatin, and FOLFIRINOX. For long-term efficacy, the 12-month overall survival (OS) rate for FOLFIRINOX was higher compared with Gemcitabine, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, and Gemcitabine + pemetrexed. The SUCRA revealed that FOLFIRINOX was relatively better in both short- and long-term efficacy, while Gemcitabine was relatively poorer. In both short- and long-term efficacy, FOLFIRINOX had the best short- and long-term efficacy among the 12 chemotherapy regimens while efficacy of Gemcitabine was relatively poorer in the treatment of advanced or metastatic PC.

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“…Before each chemotherapy cycle all patients underwent routine work-up including physical examination, blood tests and treatment-induced adverse effects assessment. IPCT regimens included modified FOLFOXIRI [27], GEMOX or GEMOXEL [28,29].…”

Section: Methodsmentioning

confidence: 99%

Use of Machine-Learning Algorithms in Intensified Preoperative Therapy of Pancreatic Cancer to Predict Individual Risk of Relapse

Elarre

Oyaga-Iriarte²,

et al. 2019

Cancers

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Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A R0 resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56–0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations.

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Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial

Abstract: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigations.

Cited by 23 publications

References 14 publications

Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104)

Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104)

Efficacy of different chemotherapy regimens in treatment of advanced or metastatic pancreatic cancer: A network meta‐analysis

Use of Machine-Learning Algorithms in Intensified Preoperative Therapy of Pancreatic Cancer to Predict Individual Risk of Relapse

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