Extended cycle streptozotocin/5-FU chemotherapy for maintenance therapy in pancreatic neuroendocrine tumors

Schrader, Joerg; Henes, Frank Oliver; Blaeker, Michael; Zimmermann-Fraedrich, Katharina; Pace, Andrea; Perez, Daniel; Izbicki, Jakob R.; Lohse, Ansgar W.; Benten, Daniel

doi:10.1007/s12020-019-01941-w

Cited by 8 publications

(28 citation statements)

References 18 publications

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“…Dilz et al showed a time to progression (TTP) of 19.4 months with an OS of 54.8 months in patients treated between 1998 and 2014 [15]. Krug et al and Schrader et al reported similar results; the OS was exceptionally short in the first study, most likely because of the inclusion of bronchial and CUP-NET [16,17] (Table 6). PFS and OS in our study reflected the performance of STZ CTx in progressive PanNET patients with multiple-organ manifestations.…”

Section: Discussionmentioning

confidence: 83%

“…However, there are no studies in which the current therapeutic alternatives have been available. Tumour classification, therapeutic thresholds, and alternatives differ considerably in published studies [4,[14][15][16][17]. In addition, grading based on Ki-67 has only been established as a mandatory part of NET baseline classification since 2010.…”

Section: Introductionmentioning

confidence: 99%

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Streptozocin/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy

et al. 2021

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Purpose The role of streptozocin-based chemotherapy (STZ CTx) in advanced, well-differentiated pancreatic neuroendocrine tumours (PanNET) and the best sequence of treatments in advanced PanNET are unclear. We examined the outcomes after STZ CTx in patients who had been selected according to the current therapeutic guidelines. Methods Data from 50 PanNET patients consecutively treated with STZ CTx between 2010 and 2018 were analysed. The endpoints of the study were the objective-response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results STZ CTx was the first-line treatment in 54% of patients. The PanNET grades were as follows: 6% G1, 88% G2, and 6% well-differentiated G3. The ORR was 38%. Stable disease was the best response in 38% of patients and 24% showed progressive disease. Treatment was discontinued because of toxicity in one patient. Median PFS and OS were 12 (95% confidence interval (CI), 8.5–15.5) and 38 months (95% CI, 20.4–55.6), respectively. In the Kaplan-Meier analysis, the median OS was 89 months (95% CI, 34.9–143.1) for STZ CTx as first-line therapy compared with 22 months (95% CI, 19.3–24.7; p = 0.001, log-rank test) for subsequent lines. Bone metastases negatively impacted survival (HR, 2.71, p = 0.009, univariate analysis, HR, 2.64, p = 0.015, multivariate analysis, and Cox regression). Conclusions In patients selected according to current guidelines, PFS, and OS after STZ CTx were lower than previously reported, whereas ORR was unchanged. First-line treatment was positively associated with OS and the presence of bone metastases was negatively associated with OS. Pre-treatment with targeted or peptide-receptor radionuclide therapy did not alter ORR, PFS, or OS.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Streptozocin/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy

et al. 2021

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“…In particular, in this study, the authors increased the interval between STZ/5-FU courses in responding patients to allow long-term treatment. A similar strategy was reported in a German study on patients with pNETs of different grades by Schrader et al, [ 38 ] where an extended cycle length (3 months) was administered as maintenance therapy after achieving disease control, which was associated with an mOS as long as 69 months. Whether patients achieving disease control with STZ/5-FU may have a higher benefit in terms of survival, safety, and quality of life by continuing the therapy (as in our patients), by increasing the interval between STZ/5-FU courses, as in the above-mentioned studies, or by stopping the therapy is not known.…”

Section: Discussionmentioning

confidence: 90%

Long-term treatment with streptozocin/5-fluorouracil chemotherapy in patients with metastatic pancreatic neuroendocrine tumors

et al. 2022

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Rationale: Pancreatic neuroendocrine tumors (pNETs) are rare entities representing 1% to 3% of all malignant pancreatic neoplasms. Current guidelines recommend a combination of streptozocin (STZ) and 5-fluorouracil (5-FU) for patients with metastatic well-differentiated pNETs requiring systemic therapy. The highest median progression-free survival rate reported in previous studies for this combination was 23 months (95% confidence interval 14.5–31.5). However, it remains unclear for how long this regimen can be safely administered. Patient concerns: We report about 3 therapy-naïve patients with metastatic G2 (Ki67 10%–15%) pNETs treated with STZ/5-FU, that achieved sustained disease control for longer than 36 months. Diagnosis: Metastatic, well-differentiated G2 pNETs Interventions: Systemic chemotherapy with STZ/5-FU was administered until the disease progressed. In 1 case showing a mixed response, selected metastases of increasing size were additionally treated with surgery and brachytherapy. Outcomes: In our 3 patients with metastatic G2 pNETs, STZ/5-FU induced long-term disease control over 44, 42, and 95 months, respectively. No side effects that led to treatment discontinuation were observed. Lessons: In patients with metastatic G2 pNETs achieving disease control, STZ/5-FU can be safely administered.

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“…Poorer performance status is reported to be significantly associated with decreased PFS/OS with chemotherapy in panNEN patients [ 302 , 303 , 304 , 305 , 306 , 307 ], as well as those with G3 tumors [ 298 , 308 ] ( Table 4 ). Higher age [ 304 , 305 , 309 , 310 , 311 ] and the prior lack of primary tumor resection [ 302 , 306 , 312 , 313 ] are also reported to correlate with worse outcomes with chemotherapy, while the effect of functional status remains controversial [ 302 , 312 ].…”

Section: Predictive Factors For Response To Chemotherapy In Advanced ...mentioning

confidence: 99%

“…Like the predictive factors for other treatment modalities, as mentioned earlier, patients who achieved radiological response had longer PFS [ 306 , 313 , 314 ], whereas those who achieved disease stabilization had longer survival [ 306 ]. Several studies reported that prior chemotherapy was significantly associated with worse outcomes with regard to another course of other chemotherapies [ 229 , 302 , 303 , 310 , 311 , 317 , 318 ].…”

Section: Predictive Factors For Response To Chemotherapy In Advanced ...mentioning

confidence: 99%

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

Lee

Ramos-Álvarez

Jensen

2022

Cancers

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Purpose: Recent advances in the diagnosis, management and nonsurgical treatment of patients with advanced pancreatic neuroendocrine neoplasms (panNENs) have led to an emerging need for sensitive and useful prognostic factors for predicting responses/survival. Areas covered: The predictive value of a number of reported prognostic factors including clinically-related factors (clinical/laboratory/imaging/treatment-related factors), pathological factors (histological/classification/grading), and molecular factors, on therapeutic outcomes of anti-tumor medical therapies with molecular targeting agents (everolimus/sunitinib/somatostatin analogues), chemotherapy, radiological therapy with peptide receptor radionuclide therapy, or liver-directed therapies (embolization/chemoembolization/radio-embolization (SIRTs)) are reviewed. Recent findings in each of these areas, as well as remaining controversies and uncertainties, are discussed in detail, particularly from the viewpoint of treatment sequencing. Conclusions: The recent increase in the number of available therapeutic agents for the nonsurgical treatment of patients with advanced panNENs have raised the importance of prognostic factors predictive for therapeutic outcomes of each treatment option. The establishment of sensitive and useful prognostic markers will have a significant impact on optimal treatment selection, as well as in tailoring the therapeutic sequence, and for maximizing the survival benefit of each individual patient. In the paper, the progress in this area, as well as the controversies/uncertainties, are reviewed.

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Extended cycle streptozotocin/5-FU chemotherapy for maintenance therapy in pancreatic neuroendocrine tumors

Cited by 8 publications

References 18 publications

Streptozocin/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy

Streptozocin/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy

Long-term treatment with streptozocin/5-fluorouracil chemotherapy in patients with metastatic pancreatic neuroendocrine tumors

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

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