8.4 Pediatric Use
The safety and effectiveness of oxaliplatin in pediatrics have not been established. Safety and effectiveness were assessed across 4 open-label studies in 235 patients aged 7 months to 22 years with solid tumors.
In a multicenter, open-label, non-comparative, non-randomized study (ARD5531), oxaliplatin was administered to 43 patients with refractory or relapsed malignant solid tumors, mainly neuroblastoma and osteosarcoma. The dose limiting toxicity (DLT) was sensory neuropathy at a dose of 110 mg/m2. The main adverse reactions were: paresthesia (60%, grade 3–4: 7%), fever (40%, grade 3–4: 7%), and thrombocytopenia (40%, grade 3–4: 27%). No responses were observed.
In an open-label non-randomized study (DFI7434), oxaliplatin was administered to 26 pediatric patients with metastatic or unresectable solid tumors, mainly neuroblastoma and ganglioneuroblastoma. The DLT was sensory neuropathy at a dose of 160 mg/m2. No responses were observed.
In an open-label, single-agent study (ARD5021), oxaliplatin was administered to 43 pediatric patients with recurrent or refractory embryonal CNS tumors. The most common adverse reactions reported were: leukopenia (67%, grade 3–4: 12%), anemia (65%, grade 3–4: 5%), thrombocytopenia (65%, grade 3–4: 26%), vomiting (65%, grade 3–4: 7%), neutropenia (58%, grade 3–4: 16%), and sensory neuropathy (40%, grade 3–4: 5%).
In an open-label single-agent study (ARD5530), oxaliplatin was administered to 123 pediatric patients with recurrent solid tumors, including neuroblastoma, osteosarcoma, Ewing sarcoma or peripheral PNET, ependymoma, rhabdomyosarcoma, hepatoblastoma, high grade astrocytoma, brain stem glioma, low grade astrocytoma, malignant germ cell tumor and other tumors. The most common adverse reactions reported were: sensory neuropathy (52%, grade 3–4: 12%), thrombocytopenia (37%, grade 3–4: 17%), anemia (37%, grade 3–4: 9%), vomiting (26%, grade 3–4: 4%), increased ALT (24%, grade 3–4: 6%), increased AST (24%, grade 3–4: 2%), and nausea (23%, grade 3–4: 3%).
The pharmacokinetic parameters of ultrafiltrable platinum were evaluated in 105 pediatric patients during the first cycle. The mean clearance in pediatric patients estimated by the population pharmacokinetic analysis was 4.7 L/h (%CV, 41%). Mean platinum pharmacokinetic parameters in ultrafiltrate were Cmax of 0.75 ± 0.24 mcg/mL, AUC0–48h of 7.52 ± 5.07 mcg∙h/mL and AUCinf of 8.83 ± 1.57 mcg∙h/mL at 85 mg/m2 of oxaliplatin and Cmax of 1.10 ± 0.43 mcg/mL, AUC0–48h of 9.74 ± 2.52 mcg∙h/mL and AUCinf of 17.3 ± 5.34 mcg∙h/mL at 130 mg/m2 of oxaliplatin.
8.5 Geriatric Use
In the adjuvant treatment trial [see Clinical Studies (14.1)], 400 patients who received Oxaliplatin with fluorouracil/leucovorin were greater than or equal to 65 years. The effect of Oxaliplatin in patients greater than or equal to 65 years was not conclusive. Patients greater than or equal to 65 years receiving Oxaliplatin experienced more diarrhea and grade 3–4 neutropenia (45% vs 39%) compared to patients less than 65 years.
In the previously untreated advanced colorectal cancer trial [see Clinical Studies (14.2)], 99 patients who received Oxaliplatin with fluorouracil and leucovorin were greater than or equal to 65 years. The same efficacy improvements in response rate, time to tumor progression, and overall survival were observed in the greater than or equal to 65 years patients as in the overall study population. Adverse reactions were similar in patients less than 65 and greater than or equal to 65 years, but older patients may have been more susceptible to diarrhea, dehydration, hypokalemia, leukopenia, fatigue, and syncope.
In the previously treated advanced colorectal cancer trial [see Clinical Studies (14.3)], 55 patients who received Oxaliplatin with fluorouracil and leucovorin were greater than or equal to 65 years. No overall differences in effectiveness were observed between these patients and younger adults. Adverse reactions were similar in patients less than 65 and greater than or equal to 65 years, but older patients may have been more susceptible to diarrhea, dehydration, hypokalemia, and fatigue.
No significant effect of age on the clearance of ultrafiltrable platinum has been observed [see Clinical Pharmacology (12.3)].