Impact of pyridoxine and vitamin E combination in preventing vincristine associated neurotoxicity in paediatric patients with hematolymphoid malignancies during induction phase of chemotherapy: A Randomized Control Trial

Leukemia’s  account for approximately 40-50% of childhood cancer burden in India with acute lymphoblastic leukemia being the commonest type. Acute lymphoblastic leukemia accounts for approximately 77% of cases of childhood leukemias. Lymphoblastic lymphoma accounts for 30-40 % . The recent advances in the treatment of leukemia and lymphoblastic lymphoma have resulted in significant improvement in cure rate of childhood malignancies but treatment related morbidities are still a challenge.   Treatment of ALL and lymphoblastic lymphoma  consists of 5 phases, which includes, Induction, Consolidation, Interim maintenance, Delayed intensification and Maintenance. First phase also known as remission induction, involves treatment for approximately 4 weeks depending on different protocols. This is the most important phase which aims to eradicate the malignant cells from bone marrow thus restoring normal hematopoiesis. The drugs used in this phase are vincristine, l-asparginase, daunorubicin, intrathecal methotrexate and steroids.Chemotherapeutic regimen completion with proper dose and adequate duration is crucial in determining the survival of patients with ALL and lymphoblastic lymphoma. Unfortunately, chemotherapy related toxicities significantly limits the dose and numbers of chemotherapy and may lead to interruption, dose reduction or even premature termination of treatment thus jeopardizing the treatment outcome.  Vincristine associated neurotoxicities are one of the most challenging and complex complications of chemotherapy .Vincristine  are Vinca alkaloids, a class of microtubule targeting agent that interferes with continuous mitotic  divison and cell growth of cancer cells. It is one of the most neurotoxic antineoplastic medicines.  Vincristine induced peripheral neurotoxicity (VIPN) is common side effect in paediatric cancer patients accounting for 45% of neuropathy incidence. Vincristine causes central nervous system and cranial nerves toxicities like ptosis, opthalmoplegia, blindness, blurred vison, diplopia, ocular muscle paresis, ototoxicity, SIADH, seizure. Muscular weakness in lower extremities, constipation, jaw pain, hoarseness were some of the other toxicities. VIPN develops due to neurodegenerative and oxidative stress. Moreover, neurotoxicity has negative impact on patient’s quality of life. Several measures like glutamic acid, B12, amitriptyline, pyridoxine and pyridostigmine have been used to treat vincristine induced peripheral neuropathy(VIPN). However, there is paucity of literature regarding the role of vitamin E and pyridoxine combination in prevention of VIPN. Vitamin B6 is an essential cofactor in synthesis of myelin sheath. It also has antioxidant property. There have been several randomized phase II studies looking at Vitamin E as neuroprotective agent. So we plan this study to determine whether vitamin B6 and vitamin E can prevent and or reduce the severity of vincristine induced neurotoxicity during induction phase of ALL and lymphoblastic lymphoma  which can eventually reduce treatment interruptions and morbidities during the most crucial phase of treatment, thus improving the treatment outcome.