Bortezomib-induced paralytic ileus is a potential gastrointestinal side effect of this first-in-class anticancer proteasome inhibitor

Perfetti, Vittorio; Palladini, Giovanni; Brunetti, Laura; Sgarella, Adele; Brugnatelli, Silvia; Gobbi, Paolo G.

doi:10.1097/meg.0b013e32811ebffe

Cited by 20 publications

(6 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although significant progress in the treatment of gliomas with surgery, radiotherapy and chemotherapy has been made, the clinical treatment of gliomas is still far from satisfactory due to their multiple types, invasiveness and difficulty to completely remove them with surgery [4]. The treatment of gliomas with post-operative radiotherapy and chemotherapy is generally accepted, but the tolerance of tumor cells to the radiotherapy may promote the relapse of residual nidus [5]; Numerous anticancer drugs have been studied and developed at home and abroad, but they can induce more adverse reactions and their therapeutic effects are not satisfactory [6,7]. In recent years, many scholars have come to believe that the anti-tumor treatment possible with Traditional Chinese Medicine is unique, and the screening of anti-tumor active ingredients and lead compounds from Traditional Chinese Medicines has become a hot topic in this field [8,9].…”

Section: Introductionmentioning

confidence: 99%

Effects of Platycodin D on Proliferation, Apoptosis and PI3K/Akt Signal Pathway of Human Glioma U251 Cells

Sun

Gao

et al. 2014

Molecules

View full text Add to dashboard Cite

Effects of platycodin D (PD) on the proliferation, apoptosis and PI3K/Akt signaling pathway of human glioma U251 cells were investigated. Glioma U251 cells were treated with PD at final concentrations of 0, 16.3, 40.8, 81.6, 163.2 μM, and inhibition rate, early and late apoptotic rate, apoptotic index, expression of apoptosis-related proteins and phosphorylation of the PI3K/Akt signaling pathway were evaluated. The results showed that compared with the control group, PD could increase the proliferation inhibition rate of U251 cells in a dose-and time -dependent manner; PD could also elevate the early and late apoptotic rate, apoptotic index and the level of pro-apoptotic proteins of glioma U251 cells, such as Bax and cleaved caspase-3, but lower the level of apoptosis inhibitory protein, such as Bcl-2; PD could increase the ratio of G0/G1 phase U251 cells, and lower the proportion of Sphase U251 cells and the ratio of G2/M phase U251 cells; PD could reduce the ratio of p-Akt/Akt. The results indicate that PD can inhibit the proliferation, induce the apoptosis and cause the cell cycle arrest in human glioma U251 cells, which may be related to the inhibition of PD on the activation of PI3K/Akt signaling pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of Platycodin D on Proliferation, Apoptosis and PI3K/Akt Signal Pathway of Human Glioma U251 Cells

Sun

Gao

et al. 2014

Molecules

View full text Add to dashboard Cite

show abstract

“…The pathophysiology of cases precipitated by immunosuppressive therapy and antineoplastic agents is less well elucidated, but it appears likely that cerebral vasospasm and subsequent ischaemia and oedema remain key processes. Bortezomib is well known to cause neuropathy, including an autonomic form in which involvement of the gastrointestinal neural plexus can result in intestinal ileus 16 . We postulate that autonomic dysfunction and cerebral vasoconstriction may both be implicated in the occurrence of RPES with the use of bortezomib.…”

Section: Discussionmentioning

confidence: 89%

Reversible posterior encephalopathy syndrome associated with bortezomib

Terwiel¹,

Hanrahan²,

Lueck

et al. 2010

Internal Medicine Journal

View full text Add to dashboard Cite

Reversible posterior encephalopathy (RPES) is an uncommon neurological syndrome that is being increasingly reported in association with anti-neoplastic therapies. The first case of reversible posterior encephalopathy associated with the proteosome inhibitor bortezomib is described and the reported experience of the occurrence of RPES with other antineoplastic therapies reviewed. Dysregulation of cerebral vasomotor autoregulation is postulated as the underlying pathophysiology in this case of bortezomib associated RPES.

show abstract

“…32 In addition, bortezomib has been associated with paralytic ileus in several cases. 33,34 We therefore suspected that the combination of etoposide and bortezomib might have contributed to poor bowel motility and increased the risk of intestinal bacteria translocation and sepsis.…”

Section: Remains Incurable Despite Recent Advances In Therapymentioning

confidence: 99%

A phase II study of V-BEAM as conditioning regimen before second auto-SCT for multiple myeloma

Fiala

et al. 2014

Bone Marrow Transplant

View full text Add to dashboard Cite

High-dose melphalan has been the standard conditioning regimen for auto-SCT in multiple myeloma (MM) for decades. A more effective conditioning regimen may induce deeper responses and longer remission duration. It is especially needed in the setting of second auto-SCT, which rarely achieves comparable results with the first auto-SCT using the same conditioning regimen. Here we conducted a phase II study to investigate the efficacy and safety of a conditioning regimen V-BEAM (bortezomib-BEAM) before second auto-SCT for multiple myeloma. Ten patients were enrolled from September 2012 to May 2013. The CR rate at day +100 after auto-SCT was 75%; all except for one patient remained in remission after a median follow-up of 6 months. Three patients developed Clostridium difficile infection. Two patients died within the first 30 days of auto-SCT from neutropenic colitis and overwhelming sepsis, respectively. Due to the high rate of morbidity and mortality, the study was terminated after 10 patients. In summary, although the conditioning regimen V-BEAM before second auto-SCT for MM provided promising responses, it was associated with unexpected treatment-related toxicity and should not be investigated further without modifications. INTRODUCTIONMultiple myeloma (MM) is the second most common hematological malignancy in the United States, accounting for more than 22 000 new cases and over 10 500 deaths in 2013. 1 Treatment with high-dose chemotherapy and auto-SCT results in improved overall response rates (ORRs), CR rates, PFS and OS compared with treatment with standard dose chemotherapy. 2 Recent studies have shown that lenalidomide maintenance therapy after auto-SCT further prolongs PFS. 3,4 Despite the benefits of auto-SCT and lenalidomide maintenance, MM remains incurable, with the median PFS after auto-SCT of 41-46 months. 3,4 For patients who relapse after auto-SCT, a second auto-SCT could be considered for salvage therapy. Several retrospective studies have demonstrated that the median PFS after a second auto-SCT is reduced by at least 50% when compared with that of the first auto-SCT. 5-9 Therefore, salvage auto-SCT provides more benefit to patients who maintain a remission for more than 2 years after the first auto-SCT, 10,11 and in practice, is often reserved only for such patients.High-dose melphalan (HDM, 200 mg/m 2 ) has remained the standard auto-SCT conditioning regimen in MM for more than 10 years 12 as no other conditioning regimens have shown superiority over HDM because of additive toxicities. [13][14][15] In patients who relapse after a first auto-SCT with HDM, a different conditioning regimen may overcome resistance to melphalan, resulting in improved ORR, PFS and OS. With a more effective conditioning regimen, a second auto-SCT may benefit more patients, including those with a short PFS after the first auto-SCT.Bortezomib is effective in treating patients with newly diagnosed or refractory/relapsed MM. Recently, several clinical

show abstract

Bortezomib-induced paralytic ileus is a potential gastrointestinal side effect of this first-in-class anticancer proteasome inhibitor

Cited by 20 publications

References 11 publications

Effects of Platycodin D on Proliferation, Apoptosis and PI3K/Akt Signal Pathway of Human Glioma U251 Cells

Effects of Platycodin D on Proliferation, Apoptosis and PI3K/Akt Signal Pathway of Human Glioma U251 Cells

Reversible posterior encephalopathy syndrome associated with bortezomib

A phase II study of V-BEAM as conditioning regimen before second auto-SCT for multiple myeloma

Contact Info

Product

Resources

About