Safety and tolerability of oral metronomic chemotherapy in pediatric malignancies using structured toxicity monitoring

Background: Oral metronomic chemotherapy (OMCT) is used in pediatric oncology as a low-toxicity, outpatient treatment alternative, particularly in resource-limited settings. Aims and Objectives: This study aimed to evaluate the hematologic and non-hematologic toxicity profile of OMCT in children with solid and hematologic malignancies. Materials and Methods: In this prospective observational study, 133 pediatric patients aged 1–18 years with advanced or relapsed malignancies were treated with a standardized OMCT regimen consisting of low-dose oral cyclophosphamide, methotrexate, etoposide, and 6-mercaptopurine. Patients were monitored monthly for 6 months for treatment-related adverse events (AEs). Toxicities were graded according to the Common Terminology Criteria for AEs (v5.0), and hematological parameters were analyzed using repeated measures analysis of variance. Results: OMCT was generally well tolerated. Grade 3–4 hematologic toxicities were observed in a minority of patients: anemia (7.5%), neutropenia (6.8%), and thrombocytopenia (4.5%). Hemoglobin levels declined transiently at 3 months (mean: 8.34±1.34 g/dL) with partial recovery by 6 months (8.86±1.45 g/dL). Among non-hematologic toxicities, fever (92.5%), loss of appetite (89.5%), fatigue (88.7%), and pain (63.9%) were most common. Mucositis (10.5%) and bruising (12%) were also noted, but no cases of febrile neutropenia or treatment-related mortality occurred. Only one patient (0.8%) discontinued therapy due to grade 4 toxicity. Conclusion: OMCT demonstrated a favorable safety profile in children with difficult-to-treat cancers, with most adverse effects being low-grade and manageable in the outpatient setting. These findings reinforce its suitability as a palliative or maintenance strategy in pediatric oncology, especially in low-resource environments.