Vincristine Induced Peripheral Neuropathy: A Randomized Controlled Trial Comparing Bolus Injections with One Hour Infusions during Induction in a Pediatric Population of Acute Lymphoblastic Leukemia and Hodgkin's Lymphoma
Authors: Velde Mirjam Esther , van den Berg Machteld Heleen , Abbink Floor , Segers Heidi , De Moerloose Barbara , van den Heuvel-Eibrink Marry M. , van den Bos Cor , van der Sluis Inge M. , Kaspers Gertjan Johannes Laurentius 
Published: October 2019

Purpose

Vincristine (VCR) is a commonly used drug in the treatment of several pediatric cancers. Unfortunately, children suffer from dose-limiting vincristine-induced peripheral neuropathy (VIPN). We aimed to assess whether the administration of VCR by means of one-hour infusions, resulting in lower peak levels, leads to less VIPN than bolus injections in children having completed the induction phase of their treatment for acute lymphoblastic leukemia (ALL) or Hodgkin's lymphoma (HL).

Methods

The study is part of the VINCA trial, an international randomized controlled trial studying the effect of administration method of VCR on the development and severity of VIPN during treatment of several types of childhood cancer. Participants were measured 3-6 times (depending on the number of VCR administrations and the total treatment period) and one final measurement 6 months after cessation of therapy. VIPN was assessed using the pediatric modified total neuropathy scale (ped-mTNS) and four items of the common toxicity criteria of adverse events (CTCAE version 4.03) items: constipation, peripheral sensory neuropathy, peripheral motor neuropathy and neuralgia. For the current analysis two measurements were taken into account. The first measurement was performed before onset of VCR therapy and the second after induction at day 33 (after 4 VCR administrations) in case of ALL or in week 7 (after 6 VCR administrations) in case of HL. VIPN was defined as a CTCAE sum score of ≥ 2 and/or a total ped-mTNS score of ≥ 5, whereas severe PNP was defined as an individual CTCAE item score of ≥ 3 or a total ped-mTNS score of ≥ 10. Analysis were done using logistic regression or cox-regression. Results were corrected for age, gender and ethnicity.

Results

In total, 91 children participated in the study, 58 (64%) of whom were treated for ALL and 18 (20%) for HL. 15 (20%) dropped out of the trial or could not be included in the current analysis due to insufficient data (n=6 drop-out or no measurements available after induction, n=9 time between measurement was larger than 64 days). Of the remaining 61, 35 (57%) were randomized in the bolus group and 26 (43%) in the one-hour group. Overall, there was a mean increase of 2.77 for the CTCAE sum score and 7.81 for the ped-mTNS sum score in the bolus group, compared to 2.12 and 6.38, respectively, in the one-hour group (CTCAE: β=-0.71, CI: -1.7-0.44, ped-mTNS: β=-0.84, CI=-3.65-1.97). 27 (77%) children developed neuropathy in the bolus group and 19 (73%) in the one-hour group. Children in the bolus group had a slightly increased, but not significant, risk of developing VIPN compared to children in the one-hour group (hazard ratio=1.21; 95% CI: 0.66 - 2.20). The proportion of children with severe neuropathy was equal in both groups (42%).

Conclusions

Children treated for ALL or HL who receive VCR by means of one-hour infusions or bolus injections seem to be at equal or diminished risk of developing VIPN during induction therapy. Results of longer follow-up that includes the total treatment period should demonstrate whether VIPN occurs less frequently and/or is less severe in case VCR is administered through one-hour infusions compared to administrations by bolus injections.

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Disclosures

No relevant conflicts of interest to declare.