What is the efficacy of metronomic chemotherapy following carboplatin (Carboplatin) treatment for osteosarcoma in canines that have undergone limb amputation?

From the Guidelines

Metronomic chemotherapy is a viable option for dogs with osteosarcoma following limb amputation and carboplatin treatment, with a recommended protocol involving low-dose oral cyclophosphamide and a non-steroidal anti-inflammatory drug (NSAID). The most recent and highest quality study, 1, provides guidance on the treatment of osteosarcoma, including the use of chemotherapy and surgery. According to this study, doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide have anti-tumor activity in osteosarcoma, and multimodal chemotherapy treatment is preferred.

Key Considerations

• The study 1 highlights the importance of staging, including local imaging studies, and curative treatment of high-grade osteosarcoma consisting of chemotherapy and surgery.
• The use of metronomic chemotherapy, as described in the example answer, is supported by the principle of targeting the tumor's blood supply and modulating the immune system, rather than directly killing cancer cells.
• The combination of cyclophosphamide and NSAIDs provides synergistic effects, with cyclophosphamide inhibiting regulatory T-cells and NSAIDs reducing pro-angiogenic factors and providing pain control.

Recommended Protocol

• Low-dose oral cyclophosphamide at 10-15 mg/m² daily or every other day, combined with a non-steroidal anti-inflammatory drug (NSAID) such as piroxicam (0.3 mg/kg daily) or meloxicam (0.1 mg/kg daily).
• Regular monitoring every 2-4 weeks initially, then every 1-3 months once stable, including complete blood counts, urinalysis, and biochemistry panels to assess organ function.

Rationale

The recommended protocol is based on the principle of metronomic chemotherapy, which targets the tumor's blood supply and modulates the immune system, rather than directly killing cancer cells. This approach typically has fewer severe side effects than conventional chemotherapy, making it well-tolerated for long-term use. The combination of cyclophosphamide and NSAIDs provides synergistic effects, making this protocol particularly valuable for maintenance therapy after completing standard-of-care treatment to help prevent or delay metastasis.

From the Research

Efficacy of Metronomic Chemotherapy

• The efficacy of metronomic chemotherapy following carboplatin treatment for osteosarcoma in canines that have undergone limb amputation is a topic of interest in veterinary medicine.
• A study published in 2018 2 found that maintenance metronomic cyclophosphamide chemotherapy following limb amputation and completed carboplatin chemotherapy was associated with no increase in progression-free time or overall survival time in dogs with appendicular osteosarcoma.
• Another study published in 2015 3 evaluated the impact of toceranib/piroxicam/cyclophosphamide maintenance therapy on the outcome of dogs with appendicular osteosarcoma following amputation and carboplatin chemotherapy, and found that the addition of toceranib to metronomic piroxicam/cyclophosphamide therapy did not improve median disease-free interval, overall survival, or the 1-year survival rate.

Adverse Events and Outcomes

• Adverse events and outcomes in dogs with appendicular osteosarcoma treated with limb amputation and a single subcutaneous infusion of carboplatin were evaluated in a study published in 2019 4, which found that the median survival time was 196 days, and the metastasis-free interval was 197 days.
• A study published in 2012 5 found that a single subcutaneous infusion of carboplatin as adjuvant chemotherapy for dogs with osteosarcoma resulted in a median survival time of 365 days, with adverse effects including bone marrow-related effects, gastrointestinal effects, and infections at the surgical site.
• A study published in 2004 6 found that alternating carboplatin and doxorubicin as adjunctive chemotherapy to amputation or limb-sparing surgery in the treatment of appendicular osteosarcoma in dogs resulted in a median progression-free survival of 227 days, and a median overall survival of 320 days.

Comparison of Treatment Protocols

• The studies suggest that different treatment protocols, including metronomic chemotherapy and single subcutaneous infusion of carboplatin, have varying degrees of efficacy and adverse events in dogs with appendicular osteosarcoma.
• A comparison of the studies 2, 5, 3, 6, 4 suggests that the choice of treatment protocol may depend on various factors, including the individual dog's health status, tumor characteristics, and owner preferences.