Lack of neuroprotection by an ACTH (4?9) analogue. A randomized trial in patients treated with vincristine for Hodgkin?s or non-Hodgkin?s lymphoma

Koeppen, Susanne; Verstappen, C.C.P.; Korte, Rodolfo Luis; Scheulen, M. E.; Strumberg, Dirk; Postma, Tjeerd J.; Heimans, Jan J.; Huijgens, Peter C.; Kiburg, B.; Renzing-Köhler, K.; Diener, H.‐C.

doi:10.1007/s00432-003-0524-9

Cited by 31 publications

(19 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acetyl‐L‐carnitine, despite preliminary reports and supporting animal tumor data, actually appeared to worsen CIPN in patients who were receiving paclitaxel‐based therapy . Two reasonably sized, placebo‐controlled, double‐blinded clinical trials demonstrated no benefit for an adrenocorticotropic hormone derivative despite 4 smaller pilot trials that suggested a benefit …”

Section: Discussionmentioning

confidence: 98%

North Central Cancer Treatment Group/Alliance trial N08CA—the use of glutathione for prevention of paclitaxel/carboplatin‐induced peripheral neuropathy: A phase 3 randomized, double‐blind, placebo‐controlled study

Leal

Qin

Atherton

et al. 2014

Cancer

View full text Add to dashboard Cite

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy. Methods 185 patients undergoing treatment with paclitaxel and carboplatin were accrued between 12/04/2009 and 12/19/2011. Patients were randomized to receive either placebo (n=91) or 1.5 g/m2 glutathione (n=94) over 15 minutes immediately prior to chemotherapy. CIPN was assessed using the EORTC-CIPN20 sensory subscale and the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Results There were no statistically significant differences between the two study arms with regard to 1) peripheral neurotoxicity, assessed utilizing both EORTC-QLQ-CIPN20 (p=0.21) and CTCAE scales (p=0.449 for grade 2+ neurotoxicity; p=0.039 for time to development of grade 2+ neuropathy, in favor of the placebo); 2) the degree of the paclitaxel acute pain syndrome (p=0.30 for patients who received every 3–4 week paclitaxel vs. p=0.002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (p=0.63); or 4) apparent toxicities. Subgroup analysis did not reveal any evidence of benefit in any particular subgroup. Conclusion This study does not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN.

show abstract

Section: Discussionmentioning

confidence: 98%

North Central Cancer Treatment Group/Alliance trial N08CA—the use of glutathione for prevention of paclitaxel/carboplatin‐induced peripheral neuropathy: A phase 3 randomized, double‐blind, placebo‐controlled study

Leal

Qin

Atherton

et al. 2014

Cancer

View full text Add to dashboard Cite

show abstract

“…52 Melanocortins are known to be present in degenerating nerves after injury 53 and promote neurite outgrowth even in the absence of nerve growth factor. 54 Though cisplatin-induced changes in nerve conduc- 58,59 Sodium thiosulfate has been demonstrated to provide central nervous system protection (ototoxicity) with chemotherapeutic agents that breach the blood-brain barrier. 60 The mechanism by which it confers protection in the peripheral nervous system is not known, but at least one human trial with cisplatin showed very low toxicity.…”

Section: Proposed Neuroprotective Agentsmentioning

confidence: 99%

Neuroprotection During Chemotherapy

Walker

Ni²

2007

American Journal of Clinical Oncology

View full text Add to dashboard Cite

The development of neurotoxicity during antineoplastic therapy is one of the most common reasons for termination or modification of cancer treatment. A number of different agents have been proposed to provide neuroprotection without affecting antitumor efficacy. This review provides an evidence-based summary of neuroprotective medicines, an overview of the literature relating to neuroprotection during cancer treatment and a Neurologist perspective risk assessment and management. Through a systematic review the authors identified 49 papers published to date that report human clinical trials involving potential neuroprotectants in adults. Case reports and series completed in a prospective fashion were also included. Sensory neuropathies were the most prevalent subtype in the literature, and most were at least partially reversible with or without neuroprotective treatment. The majority of study medications had minimal side effects, though 2 trials were prematurely terminated because of adverse patient outcomes. No study reported an effect on antitumor efficacy. Because of the variability in study design, cancer type, outcome measures, and clinical confirmation of neuropathy, meta-analysis could not be appropriately performed. We highlight risk factors and discuss neuropathy screening. Descriptive analysis is provided which reveals that many of the agents studied were likely to confer some at least some neuroprotective benefit.

show abstract

“…To date, multiple avenues of neuroprotective intervention have been investigated with concurrent cisplatin use including vitamin E (Pace et al, 2003; Pace et al, 2007; Pace et al, 2010), Glutathione (Cascinu et al, 1995; Smyth et al, 1997) and Org 2766, an adrenocorticotrophic hormone analogue (Koeppen et al, 2004; van der Hoop et al, 1990a). However, clinical success has been minimal; leaving dose reductions or alterations in dose scheduling the only option for patients.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of cisplatin-induced experimental peripheral neuropathy by a small molecule targeting p75NTR

Friesland¹,

Weng²,

Dueñas³

et al. 2014

NeuroToxicology

View full text Add to dashboard Cite

Cisplatin is an effective and widely used first-line chemotherapeutic drug for treating cancers. However, many patients sustain cisplatin-induced peripheral neuropathy (CIPN), often leading to a reduction in drug dosages or complete cessation of treatment altogether. Therefore, it is important to understand cisplatin mechanisms in peripheral nerve tissue mediating its toxicity and identify signaling pathways for potential intervention. Rho GTPase activation is increased following trauma in several models of neuronal injury. Thus, we investigated whether components of the Rho signaling pathway represent important neuroprotective targets with the potential to ameliorate CIPN and thereby optimize current chemotherapy treatment regimens. We have developed a novel CIPN model in the mouse. Using this model and primary neuronal culture, we determined whether LM11A-31, a small-molecule, orally bioavailable ligand of the p75 neurotrophin receptor (p75NTR), can modulate Rho GTPase signaling and reduce CIPN. Von Frey filament analysis of sural nerve function showed that LM11A-31 treatment prevented decreases in peripheral nerve sensation seen with cisplatin treatment. Morphometric analysis of harvested sural nerves revealed that cisplatin-induced abnormal nerve fiber morphology and the decreases in fiber area were alleviated with concurrent LM11A-31 treatment. Cisplatin treatment increased RhoA activity accompanied by the reduced tyrosine phosphorylation of SHP-2, which was reversed by LM11A-31. LM11A-31 also countered the effects of calpeptin, which activated RhoA by inhibiting SHP-2 tyrosine phosphatase. Therefore, suppression of RhoA signaling by LM11A-31 that blocks proNGF binding to p75NTR or activates SHP-2 tyrosine phosphatase downstream of NGF receptor enhances neuroprotection in experimental CIPN in mouse model.

show abstract

Lack of neuroprotection by an ACTH (4?9) analogue. A randomized trial in patients treated with vincristine for Hodgkin?s or non-Hodgkin?s lymphoma

Abstract: Contrary to a single previous pilot study in patients receiving VCR-based chemotherapy, in our study the ACTH (4-9) analogue Org 2766 did not provide protection from VCR-induced neuropathy.

Cited by 31 publications

References 44 publications

North Central Cancer Treatment Group/Alliance trial N08CA—the use of glutathione for prevention of paclitaxel/carboplatin‐induced peripheral neuropathy: A phase 3 randomized, double‐blind, placebo‐controlled study

North Central Cancer Treatment Group/Alliance trial N08CA—the use of glutathione for prevention of paclitaxel/carboplatin‐induced peripheral neuropathy: A phase 3 randomized, double‐blind, placebo‐controlled study

Neuroprotection During Chemotherapy

Amelioration of cisplatin-induced experimental peripheral neuropathy by a small molecule targeting p75NTR

Contact Info

Product

Resources

About