Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors

Cives, Mauro; Ghayouri, Masoumeh; Morse, Brian; Brelsford, Marjorie; Black, Michael A.; Rizzo, Anthony; Meeker, Alan K.; Strosberg, Jonathan R.

doi:10.1530/erc-16-0147

Cited by 147 publications

(128 citation statements)

References 21 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…A Spanish multicenter study and the single-center experience of Cives et al [30] revealed very similar results in terms of response and outcome [31]. Response rates were 47.7 and 54% with additional disease stabilization rates of 41.5 and 35% respectively.…”

Section: Recently Published Studies Confirming the Role Of Chemotheramentioning

confidence: 88%

“…TEM monotherapy has a long tradition in glioblastoma and melanoma, though in PNETs it was described to have only marginal benefits [26]. Therefore, combination regimens were evaluated revealing impressive objective response rates (RR) and good tolerability for the TEM-CAP combination therapy [27,28,29,30,31]. However, due to the limited availability of data and prospective clinical trials, the current guidelines recommend the TEM-CAP combination only as an alternative but not superior treatment to STZ/5-FU.…”

Section: Current Standard Of Treatmentmentioning

confidence: 99%

“…While Kulke and coworkers [49] observed significant correlations between MGMT protein expression and response to TEM, the articles of Schmitt et al [48] and Walter et al [50] only confirmed this correlation with respect to promoter methylation status. Very recently, Cives et al [30] analyzed 143 patients treated with TEM-CAP with regard to their MGMT and ALT (alternative lengthening of telomeres) status as potential predictive biomarkers. However, treatment efficacy did not appear to be influenced by these markers.…”

Section: Predictive Markers For Chemotherapy In Pnetsmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Cytotoxic Chemotherapy in Advanced Pancreatic Neuroendocrine Tumors

Krug¹,

Gress²,

Michl³

et al. 2017

Digestion

View full text Add to dashboard Cite

Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms accounting for less than 5% of all pancreatic malignancies. These tumors are characterized by clinical and prognostical heterogeneity and are predominantly diagnosed in a metastatic stage. Cytotoxic chemotherapy, along with alkylating agents and antimetabolites as well as molecular targeted agents (everolimus, sunitinib), is used in the treatment of advanced PNETs. After the approval of lanreotide for unresectable PNETs, an additional therapeutic option has become available; however, the best sequence of therapies and patient stratification to different treatments remains challenging. Furthermore, no randomized phase-3 trials or head-to-head comparisons are available to support treatment decisions. Summary: The publication of 3 large single-center retrospective studies on streptozocin-(STZ)-based chemotherapy in advanced PNETs in 2015 confirmed the effectiveness of this treatment as described in previously reported trials. All studies investigated markers for progression-free and overall survival and strongly supported the value of the Ki-67 index as a robust prognostic marker. Interestingly, chemotherapy consistently displayed antitumor efficacy in different therapeutic lines. Moreover, a recent study of dacarbazine (DTIC) in a cohort of patients predominantly with PNETs demonstrated that a once monthly infusional DTIC schedule was well tolerated and yielded similar response rates (RR) as STZ-based schedules. Given the overall good tolerability of a monthly infusion and RR similar to STZ schedules, DTIC thus represents a feasible alternative or additional treatment option for PNETs. In this article, we review the current standard and summarize the most recent advances in the field of cytotoxic chemotherapy for PNET patients. Key Messages: (1) Despite the lack of phase3 trials, cytotoxic chemotherapy offers efficacy for patients with advanced PNETs; (2) the best therapeutic option and sequence remain open since comparable randomized studies are lacking; (3) careful patient selection and treatment stratification may increase overall outcome; and (4) currently, no biomarkers for clinical routine exist to predict response to chemotherapy.

show abstract

Section: Recently Published Studies Confirming the Role Of Chemotheramentioning

confidence: 88%

Section: Current Standard Of Treatmentmentioning

confidence: 99%

Section: Predictive Markers For Chemotherapy In Pnetsmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Cytotoxic Chemotherapy in Advanced Pancreatic Neuroendocrine Tumors

Krug¹,

Gress²,

Michl³

et al. 2017

Digestion

View full text Add to dashboard Cite

show abstract

“…As this combination is used widely in mCRC, the same safety considerations apply. A commonly applied systemic approach to metastatic NETs is an oral combination regimen of capecitabine and temozolomide (CapTem), which alone has a 60% objective response rate for well-differentiated NETs (119). A feasibility and safety study of integrated CapTem and SIRT delivered on day 7 of the 14-day cycle, demonstrated no worse than additive toxicities, with better than expected disease control in the liver, suggesting a synergy justifying expansion into a phase II trial (120).…”

Section: Netsmentioning

confidence: 99%

Safety of selective internal radiation therapy (SIRT) with yttrium-90 microspheres combined with systemic anticancer agents: expert consensus

Kennedy

Brown

Feilchenfeldt

et al. 2017

J. Gastrointest. Oncol.

View full text Add to dashboard Cite

Selective internal radiation therapy (SIRT) with microspheres labelled with the β-emitter yttrium-90 (Y-90) enables targeted delivery of radiation to hepatic tumors. SIRT is primarily used to treat inoperable primary or metastatic liver tumors. Eligible patients have usually been exposed to a variety of systemic anticancer therapies, including cytotoxic agents, targeted biologics, immunotherapy and peptide receptor radionuclide therapy (PRRT). All these treatments have potential interactions with SIRT; however, robust evidence on the safety of these potential combinations is lacking. This paper provides current clinical experiences and expert consensus guidelines for the use of SIRT in combination with the anticancer treatment agents likely to be encountered in clinical practice. It was agreed by the expert panel that precautions need to be taken with certain drugs, but that, in general, systemic therapies do not necessarily have to be stopped to perform SIRT. The authors recommend stopping vascular endothelial growth factor inhibitors 4-6 weeks before SIRT, and restart after the patient has recovered from the procedure. It may also be prudent to stop potent radiosensitizers such as gemcitabine therapy 4 weeks before SIRT, and restart treatment at least 2-4 weeks later. Data from phase III studies combining SIRT with fluorouracil (5FU) or folinic acid/5FU/oxaliplatin (FOLFOX) suggest that hematological toxicity is more common from the combination than it is from chemotherapy without SIRT. There is no evidence to suggest that chemotherapy increases SIRT-specific gastro-intestinal or liver toxicities.

show abstract

“…50% of cases) [229][230][231]. However, determination of MGMT expression or methylation state is not currently recommended as a criterion for the use of chemotherapy.…”

Section: Szkolenie Podyplomowementioning

confidence: 99%