Prevention of neuropathy using calmangafodipir (PLEDOX): Results from a phase I study and a placebo-controlled randomized study (PLIANT) in patients with metastatic colo-rectal cancer (MCRC)

B. Glimelius, D. Mahalingam, J. Gandhi, N. Manojlovic, P. Pfeiffer, B. Mosidze, A. Dudov, M. Karlberg, M. Bengtson, J. Nasstrom

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Abstrakt

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a major problem after oxaliplatin and no protective agent is available. Calmangafodipir (Karlsson, Transl Oncol 2012; 5:492), has shown promising activities in model systems in preventing oxaliplatin-induced adverse effects, without negatively interfering with the antitumor activity. Objectives: To evaluate this further, a dose-escalating phase I study and a subsequent randomized multicenter phase II study was performed to assess safety and efficacy of calmangafodipir in ameliorating CIPN. Methods: The PLIANT study included mCRC patients to be treated with the FOLFOX-6 regimen (oxaliplatin 85 mg/m2, calciumfolinate 200 mg/m2, 5FU bolus 400 mg/m2, 5FU infusion 2400 mg/m2) every fortnight. Ten minutes prior to each chemotherapy cycle calmangafodipir was given intravenously during 5 min. Neurotoxicity was evaluated according to the Oxaliplatin Sanofi Specific Scale, a Cold Allodynia Test and the Leonard Scale. Tumor evaluations were done after 4 and 8 cycles. Results: In the open part 1, 11 eligible patients were included with escalating doses of calmangafodipir 2, 5 and 10 mumol/kg. Nine patients received at least 7 of the planned number of 8 cycles and were fully evaluable. Calmangafodipir was well tolerated. Neurotoxicity was very low, with no grade II or higher toxicity compared to expected 40% after 8 cycles (Loprinzi, JCO 2014; 32:997). Cold allodynia was also low. Patient inclusion has been completed in the randomized 3-armed study (n=173). Conclusions: Early experience using a chemoprotector calmangafodipir is promising in the open phase of the PLIANTstudy. Results: from the placebo-controlled study will be presented at the meeting.
OriginalsprogEngelsk
Artikelnummer27-01-O
TidsskriftSupportive Care in Cancer
Vol/bind23
Udgave nummerSUPPL. 1
Sider (fra-til)S384-S385
ISSN0941-4355
DOI
StatusUdgivet - 2015
BegivenhedMASCC/ISOO International Symposium - Bella Center, Copenhagen, Danmark
Varighed: 25. jun. 201527. jun. 2015

Seminar

SeminarMASCC/ISOO International Symposium
LokationBella Center
LandDanmark
ByCopenhagen
Periode25/06/201527/06/2015

Emneord

  • *human *phase 1 clinical trial *neoplasm *patient *rectum cancer *neuropathy *prevention neurotoxicity chemotherapy allodynia infusion peripheral neuropathy safety phase 2 clinical trial antineoplastic activity adverse drug reaction model toxicity experience controlled study *placebo oxaliplatin fluorouracil protective agent

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