Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial) – A phase II non-randomised trial

Ducreux, Michel; Dahan, Laétitia; Smith, Denis; O’Toole, Dermot; Lepère, Céline; Dromain, Clarisse; Vilgrain, Valérie; Baudin, Éric; Lombard‐Bohas, Catherine; Scoazec, Jean‐Yves; Seitz, Jean‐François; Bitoun, Laurence; Koné, Sébastien; Mitry, Emmanuel

doi:10.1016/j.ejca.2014.10.002

Cited by 75 publications

(53 citation statements)

References 32 publications

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“…Notably, both STZ and temozolomide are alkylating agents with similar mechanisms of action; and capecitabine and 5-FU also have similar mechanisms of action [34]. Our results are comparable to a recently published study by Ducreux et al [35], indicating a PFS of 23.7 months for the combination therapy with STZ, 5-FU and bevacizumab.…”

Section: Discussionsupporting

confidence: 85%

Streptozocin and 5-Fluorouracil for the Treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity

et al. 2015

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Background: In our center,the combination of streptozocin (STZ) and 5-fluorouracil (5-FU) has been used as the first-line treatment in the majority of patients with pancreatic neuroendocrine tumors (pNETs) over the past few decades. The objective of the current study was to assess the efficacy, prognostic factors and safety of the combination of STZ and 5-FU. Patients and Methods: Medical records and radiological reports of 133 patients with pNETs who received the combination of STZ and 5-FU during the period 1981-2014 were retrospectively evaluated. Results: The median survival from the start of treatment was 51.9 months in the whole group. In the radiologically evaluable patients (n = 100), progression-free survival was 23 months. Complete response was reached in 3 patients (3%), partial response in 25 patients (25%), 64 patients (64%) had stable disease, and 8 patients (8%) had progressive disease. In a multivariate analysis, surgery of the primary tumor and having a G3 tumor were significant positive and negative prognostic factors of survival from the start of treatment, respectively. Having either a G3 tumor or a stage IV tumor were significant prognostic factors for a shorter progression-free survival. Chemotherapy had to be discontinued in 29 patients due to side effects, of which kidney toxicity (mainly grades 1-2) was the most frequent. Conclusion: As shown in recent reports, the combination of STZ and 5-FU is effective in the treatment of pNETs in terms of survival and radiological response and has an acceptable toxicity profile.

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Section: Discussionsupporting

confidence: 85%

Streptozocin and 5-Fluorouracil for the Treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity

et al. 2015

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“…For example, there are no clear data of a favorable effect when combining bevacizumab with streptozotocin in pNET or with oxaliplatin in different types of NET such as carcinoids, pancreatic NET or poorly differentiated NEC (Ducreux et al 2014.…”

Section: Combination Therapiesmentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Pavel¹,

Sers²

2016

Endocrine-Related Cancer

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Neuroendocrine tumors (NETs) are a group of heterogenous neoplasms. Evidencebased treatment options for antiproliferative therapy include somatostatin analogues, the mTOR inhibitor everolimus, the multiple tyrosine kinase inhibitor sunitinib and peptide receptor radionuclide therapy with 177-Lu-octreotate. In the absence of definite predictive markers, therapeutic decision making follows clinical and pathological criteria. As objective response rates with targeted drugs are rather low, and response duration is limited in most patients, numerous combination therapies targeting multiple pathways have been explored in the field. Upfront combination of drugs, however, is associated with increasing toxicity and has shown little benefit. Major advancements in the molecular understanding of NET based on genomic, epigenomic and transcriptomic analysis have been achieved with prognostic and therapeutic impact. New insight into molecular alterations has paved the way to biomarker-driven clinical trials and may facilitate treatment stratification toward personalized medicine in the near future. However, an improved understanding of the complexity of pathway interactions is required for successful treatment. A systems biology approach is one of the tools that may help to achieve this endeavor.

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“…Treatments were given according to recommendations and/or the main publications in the field and discussed within the setting of a multidisciplinary meeting for more than 20 years. The main characteristics of our strategy have previously been described [4,16,[20][21][22] .…”

Section: Treatmentmentioning

confidence: 99%

“…Also, three positive placebo-controlled phase III trials have recently been published in pNET patients leading to the approval of three targeted therapies: sunitinib, everolimus and lanreotide [13][14][15] . Finally, treatment combinations are now emerging [16] . At present, patients may benefit from a long list of available therapeutic options, at least nine for patients suffering from metastatic pNET [17] , and the question of the best strategy is now open for discussion.…”

Section: Introductionmentioning

confidence: 99%

Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study

Berdelou¹,

Boige

Arfi-Rouche

et al. 2016

Neuroendocrinology

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Background: At least nine therapeutic options are recommended or approved for pancreatic neuroendocrine tumour (pNET). The primary endpoint of this study was to determine the number of therapeutic lines given before death. Secondary endpoints were to determine toxic events as a function of number of therapeutic lines and of time. Methods: Patients with pNET treated between 1998 and 2010 at our centre were characterised. All therapeutic lines were recorded as well as tumour- or toxic-related deaths. Persistent treatment-related toxicity (PTRT) was defined as: chronic kidney disease, anaemia, thrombocytopenia, neutropenia, severe liver failure, cardiac failure and recurrent sepsis, precluding at least one other therapeutic option or second cancers. Results: Ninety-two patients were analysed. The median follow-up was 7 years. The 1-, 2- and 5-year overall survival rates were 90, 81 and 51%, respectively. After 3 and 5 therapeutic lines, 23 and 50% of patients had died, respectively. After 3 and 5 lines, the frequency of toxic events was 8 and 24%, respectively. Overall, 17 toxic events were observed including 6 treatment-related deaths and 11 PTRT. After 1, 2 and 5 years of treatment, the frequency of toxic events was 6, 9 and 16%, respectively. Conclusion: Tumour- and toxic-related deaths as well as PTRT may preclude access to all therapeutic options in patients with pNET. Optimised risk benefit sequence should be investigated.

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Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial) – A phase II non-randomised trial

Cited by 75 publications

References 32 publications

Streptozocin and 5-Fluorouracil for the Treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity

Streptozocin and 5-Fluorouracil for the Treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study

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