Oral metronomic chemotherapy has promising results when used in a selected cohort of patients but has dismal results in patients who failed within 6 months of previous treatment.

Osteosarcoma remains one of the most challenging cancers of childhood and young adults wherein the addition of chemotherapy to surgery has led to dramatic but improvements in the event-free survival (EFS) (from 20% to 60%). However, these improvements have been largely reported in developed nations, with a gross mismatch seen in low-and middle-income countries (LMICs). However, even in high-income countries, the outcomes are largely static since the past three decades. [1] Osteosarcoma therapy protocols mainly utilize a dyad backbone of cisplatin and doxorubicin, with the addition of a third drug, either ifosfamide or high-dose methotrexate (HDMTX), which has led to rapid strides forward in survival in osteosarcoma. [1]

No abstract

Background: Metastatic osteosarcoma outcomes are dismal, despite costly and complex high-dose methotrexate (HDMTX)-based therapies. This is challenging especially in lower and middle-income countries (LMICs) with limited resources & increasing patient volumes. We need to reallocate resources to efficient but sustainable strategies, like exploring Non-HDMTX based protocols and aggressive multimodality approach in this setting. Methods: All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the "OGS-12" protocol, which involved administration of eight sequential doublets of the three most active drugs (doxorubicin, cisplatin, and ifosfamide), universal growth factor prophylaxis and targeted nutritional support if required. Four cycles were administered as neoadjuvant therapy (NACT) followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy (ACT). Results: Four ninety-five patients were enrolled in the OGS-12 protocol from 2011 to 2016, of whom 110 (22%) had metastatic disease; the median age was 17 years. The majority of patients were nutritionally challenged with high-risk features like high LDH (80%), high SAP (91%). After NACT, 57% of patients were histologically good responders (gHR) that is 90% tumor necrosis. Five-year event-free survival (EFS) & overall survival(OS) rates were 24% & 20%, respectively, in the intent-to-treat and 43% & 29%, respectively, in the per-protocol populations. Significant grade 3/4 toxicities were febrile neutropenia (29%), thrombocytopenia (39%), and anemia (56%). Ability to perform metastectomy for improved OS, compliance to therapy for improved EFS, and gHR for both improved EFS and OS were identified as independent prognostic markers. Conclusions: Adoption of an aggressive multimodality approach including the novel, low-cost, Non-HDMTX-based, dose-dense "OGS-12" protocol, enhanced supportive care & compliance, with metastectomy resulted in internationally comparable outcomes of metastatic osteosarcoma patients. This rational and sustainable, economically efficient strategy is worthy of wide adaption.

No abstract