Vincristine-associated Neurological Morbidity in the Treatment of Hepatoblastoma

Abstract

Chemotherapy is an essential component of therapy for infants and children with hepatoblastoma. Vincristine has been a mainstay of chemotherapeutic regimens used by North American cooperative groups, based on indirect evidence of benefit and an assumption of minimal added toxicity. European cooperative group trials have reported comparable survival rates using regimens that omit vincristine. Further examination of the risk and benefit profile of vincristine relevant to hepatoblastoma clinical care paradigms is thus warranted. We evaluated the incidence of vincristine-related sensorimotor peripheral, autonomic, and cranial nerve neurological morbidities in 45 consecutive hepatoblastoma patients treated at our institution. Data suggest an increased risk of vincristine-associated neuropathic grade 2 and 3 events (neuropathic pain and gross motor impairment) in children ages 24 months old or younger, and particularly in children born prematurely. Formal prospective investigation of the relative risks and benefits of vincristine in hepatoblastoma treatment is warranted to assess the value of continued use of vincristine in this patient population.

Paclitaxel inhibits post‐traumatic recurrent laryngeal nerve regeneration into the posterior cricoarytenoid muscle in a canine model

“…In this study, we found no statistically significant difference in the effectiveness of paclitaxel or vincristine at 0 or 3 months following RLN transection/repair. Vincristine administration in the setting of chemotherapy has been associated with toxicity including neutropenia, neuropathy, and a small therapeutic window . Although low‐dose administration of vincristine following vocal fold paralysis may avoid toxicity and achieve the desired effects, paclitaxel provides an alternative with a possibly wider therapeutic index .…”

“…Vincristine administration in the setting of chemotherapy has been associated with toxicity including neutropenia, neuropathy, and a small therapeutic window. [19][20][21] Although low-dose administration of vincristine following vocal fold paralysis may avoid toxicity and achieve the desired effects, 10 paclitaxel provides an alternative with a possibly wider therapeutic index. 22 Additionally, prior studies have demonstrated that paclitaxel and vincristine have no effect after reinnervation has occurred.…”

Patient‐reported neuropathic pain in adolescent and young adult cancer patients

“…Neuropathic pain is a significant complication of pediatric and young adult cancer therapy and has substantial adverse effects on health‐related quality of life . In addition, neuropathic pain is a dose‐limiting side effect of chemotherapy that can impact the success of treatment and the overall survival . The economic burden of neuropathic pain is considerable, including increased medical costs and loss of productivity for patients and caregivers …”

“…Existing data reporting the prevalence of neuropathic pain in pediatric and young adult cancer patients are limited to retrospective chart reviews. These studies have focused on pediatric patients with acute lymphoblastic leukemia (ALL) and hepatoblastoma and found that 29–35% of the patients experienced neuropathic pain associated with receipt of vincristine . These studies are significantly limited by their retrospective nature and are only able to report on what was documented in the medical record.…”

“…4,[8][9][10] In addition, neuropathic Abbreviations: ALL, acute lymphoblastic leukemia; CI, confidence interval; CNS, central nervous system; GEE, generalized estimating equations; IQR, interquartile range; SD, standard deviation; TCA, tricyclic antidepressant pain is a dose-limiting side effect of chemotherapy that can impact the success of treatment and the overall survival. 6,11 The economic burden of neuropathic pain is considerable, including increased medical costs and loss of productivity for patients and caregivers. 12,13 Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.…”