TY  - JOUR
AU  - Boehmerle, Wolfgang
AU  - Hagenacker, Tim
AU  - Leo, Markus
AU  - Schmitt, Linda-Isabell
AU  - Lehmann, Helmar C
AU  - Klein, Ines
AU  - Stegherr, Regina
AU  - Konietschke, Frank
AU  - Endres, Matthias
AU  - Huehnchen, Petra
TI  - Results of the preclinical multicenter randomized controlled paclitaxel-induced neuropathy prevention replication study (PINPRICS).
JO  - BMC Research Notes
VL  - 18
IS  - 1
SN  - 1756-0500
CY  - London
PB  - [Verlag nicht ermittelbar]
M1  - DZNE-2025-00506
SP  - 145
PY  - 2025
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and serious side effect of many cytotoxic drugs, including paclitaxel. Despite the identification of treatment options in animal models, clinical trials for the treatment or prevention of CIPN have been negative. Major challenges for successful clinical translation of preclinical data include a lack of reproducibility and randomization, small sample sizes and insufficient statistical tests. We therefore conducted a confirmatory, preclinical multicenter randomized controlled replication trial to test the safety and efficacy of three drugs for preventing paclitaxel-induced polyneuropathy: (1) nilotinib, (2) lithium carbonate and (3) interleukin-6-neutralizing antibodies. We preregistered the data analysis plan as well as the two-step study protocol: the optimal doses of the three compounds were assessed first and then tested in a mouse breast cancer xenograft model to compare safety and efficacy.Unfortunately, toxicity of intraperitoneally administered nilotinib in combination with paclitaxel was observed, and higher-than-expected tumor growth resulted in a lack of power when the trial was analyzed. Thus, although lithium carbonate and IL-6-neutralizing antibodies tended toward neuroprotection, the differences between these groups were not statistically significant. However, the PINPRICS study ultimately still provides important lessons with regard to the planning and conduction of multicenter preclinical trials.
KW  - Paclitaxel: adverse effects
KW  - Animals
KW  - Mice
KW  - Female
KW  - Lithium Carbonate: pharmacology
KW  - Lithium Carbonate: therapeutic use
KW  - Lithium Carbonate: administration & dosage
KW  - Pyrimidines: therapeutic use
KW  - Pyrimidines: pharmacology
KW  - Pyrimidines: administration & dosage
KW  - Humans
KW  - Peripheral Nervous System Diseases: chemically induced
KW  - Peripheral Nervous System Diseases: prevention & control
KW  - Antibodies, Neutralizing: pharmacology
KW  - Antibodies, Neutralizing: therapeutic use
KW  - Interleukin-6: immunology
KW  - Interleukin-6: antagonists & inhibitors
KW  - Antineoplastic Agents, Phytogenic: adverse effects
KW  - Cell Line, Tumor
KW  - Xenograft Model Antitumor Assays
KW  - Breast Neoplasms: drug therapy
KW  - Breast Neoplasms: pathology
KW  - Chemotherapy-induced polyneuropathy (Other)
KW  - Neuropathic pain (Other)
KW  - Neuroprotection (Other)
KW  - Preclinical replication study (Other)
KW  - Paclitaxel (NLM Chemicals)
KW  - Lithium Carbonate (NLM Chemicals)
KW  - Pyrimidines (NLM Chemicals)
KW  - nilotinib (NLM Chemicals)
KW  - Antibodies, Neutralizing (NLM Chemicals)
KW  - Interleukin-6 (NLM Chemicals)
KW  - Antineoplastic Agents, Phytogenic (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40200318
DO  - DOI:10.1186/s13104-025-07206-2
UR  - https://pub.dzne.de/record/277974
ER  -