November 2022: In children aged one month and older with localised, non-metastatic solid tumours, the Food and Drug Administration has approved sodium thiosulfate (Pedmark, Fennec Pharmaceuticals Inc.) to lower the risk of ototoxicity associated with cisplatin.
Two multicenter open-label, randomised controlled studies, SIOPEL 6 (NCT00652132) and COG ACCL0431, were conducted in children receiving cisplatin-based chemotherapy for cancer (NCT00716976).
114 patients with standard risk hepatoblastoma were enrolled in SIOPEL 6 and underwent 6 cycles of postoperative cisplatin-based chemotherapy. Depending on their actual body weight, patients were randomised (1:1) to receive cisplatin-based treatment with or without sodium thiosulfate at different doses of 10 g/m2, 15 g/m2, or 20 g/m2. The majority of patients having a Brock Grade 1 hearing loss, as determined by pure tone audiometry following therapy or at the age of at least 3.5 years, whichever came first, was the primary outcome. When cisplatin was combined with sodium thiosulfate, there was a decreased incidence of hearing loss (39% vs. 68%); the unadjusted relative risk was 0.58 (95% CI: 0.40, 0.83).
Children with solid tumours who were receiving chemotherapy that included cumulative cisplatin doses of 200 mg/m2 or more and individual cisplatin doses to be administered for a maximum of six hours were included in COG ACCL0431. The administration of chemotherapy based on cisplatin with or without sodium thiosulfate was randomly assigned (1:1) to patients. A group of 77 patients with locally contained, non-metastatic solid tumours had their efficacy assessed. The American Speech-Language-Hearing Association (ASHA) criteria for hearing loss were measured at baseline and four weeks following the final treatment of cisplatin. This was the main outcome. When cisplatin was combined with sodium thiosulfate, the incidence of hearing loss was decreased (44% vs. 58%); the unadjusted relative risk was 0.75 (95% CI: 0.48, 1.18).
Vomiting, nausea, a reduction in haemoglobin, hypernatremia, and hypokalemia were the most frequent adverse effects in the two studies (25% with a difference between arms of >5% compared to cisplatin alone).
The dosage of sodium thiosulfate that is advised is based on the surface area of the body as measured by real weight. Following intravenous infusions of cisplatin that last one to six hours, sodium thiosulfate is given over the course of 15 minutes.
View full prescribing information for Pedmark.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
