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. 2023 Dec 1;15(23):5688.
doi: 10.3390/cancers15235688.

Metronomic Temozolomide (mTMZ) and Bevacizumab-The Safe and Effective Frontier for Treating Metastatic Neuroendocrine Tumors (NETs): A Single-Center Experience

Çağlar Ünal  1 , Sezer Sağlam  2
Affiliations

Metronomic Temozolomide (mTMZ) and Bevacizumab-The Safe and Effective Frontier for Treating Metastatic Neuroendocrine Tumors (NETs): A Single-Center Experience

Çağlar Ünal et al. Cancers (Basel). .

Abstract

Addressing the persistent challenges in treating metastatic neuroendocrine tumors (NETs) demands ongoing refinement and innovation in therapeutic strategies. This study investigates the potential advantages of combining metronomic temozolomide (mTMZ) with bevacizumab for patients diagnosed with metastatic NETs, particularly focusing on those with a Ki-67 index under 55%. Data from 30 patients were analyzed, using key performance indicators such as progression-free survival (PFS), overall survival (OS), and response rates to therapy, to gauge the treatment's efficacy. The results were encouraging: the median PFS recorded was 16.3 months, and the OS was 25.9 months. The disease control rate (DCR) reached an impressive 86.7%, and the objective response rate (ORR) stood at 63.3%. The treatment regimen was well-tolerated, with no reported instances of grade 4 toxicities. Such a safety profile indicates that this regimen may be particularly advantageous for older, fragile patients who might struggle with conventional dosage levels. These initial findings suggest that the mTMZ and bevacizumab combination could potentially rival the conventional temozolomide-capecitabine therapy in managing metastatic NETs. We aimed to meticulously assess the efficacy of the mTMZ and bevacizumab combination in treating metastatic NETs. Given the initial promising results, a more conclusive understanding of its efficacy will require further research through larger, multicenter prospective clinical trials.

Keywords: CAPTEM; bevacizumab; mTMZ; metronomic temozolomide; neuroendocrine neoplasia; neuroendocrine tumors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of patients identified and included in the final analysis.
Figure 2
Figure 2
Survival analysis of patients treated with mTMZ and bevacizumab.
Figure 3
Figure 3
(A) (upper) Downstaging tumors (complete response) after metronomic TMZ–bevacizumab combination therapy. MRI images for the patient with metastatic NET before (a,c) and six months after treatment (b,d); (B) (bottom) downstaging tumors (complete response) after metronomic TMZ–bevacizumab combination therapy. Gallium-68 (Ga-68)-DOTATATE positron emission tomography (PET) images for the patient with metastatic NET before (e,g) and one year after treatment (f,h).
Figure 3
Figure 3
(A) (upper) Downstaging tumors (complete response) after metronomic TMZ–bevacizumab combination therapy. MRI images for the patient with metastatic NET before (a,c) and six months after treatment (b,d); (B) (bottom) downstaging tumors (complete response) after metronomic TMZ–bevacizumab combination therapy. Gallium-68 (Ga-68)-DOTATATE positron emission tomography (PET) images for the patient with metastatic NET before (e,g) and one year after treatment (f,h).
Figure 4
Figure 4
Survival analysis of patients treated with mTMZ and bevacizumab treatment according to the grade 1, 2 vs. 3 (upper) and Ki-67 groups (≤20%, 21–55%) (bottom).
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