Trial of Pazopanib in a Multiply Relapsed Osteosarcoma Patient

Background: Osteosarcomas (OS) are typically found among adolescents and young adults and usually affect the long bones around the knee. The current treatment options for relapsed OS include surgery, chemotherapy, targeted therapy, or some combination of these modalities. Constitutive activation of tyrosine kinase mediated pathways leading to up-regulation of cell division and growth have been implicated in OS. This study identifies a patient at Cook Children’s Medical Center (CCMC) who, upon relapse, was treated with pazopanib, a multi-tyrosine kinase inhibitor, on compassionate basis, which led to stability of disease, along with treatment related toxicities. Case Information: A 25-year-old female initially presented with left femur osteosarcoma and was treated with chemotherapy consisting of methotrexate, doxorubicin and cisplatin followed by amputation and neo-adjuvant chemotherapy. Following 6 years of remission, she presented with two lung masses that were resected along with chemotherapy and radiation. After almost 2.5 years, she presented with progressive tumor in the right pleural base for which she was treated with pazopanib. She demonstrated positive response with stable size of tumor and increased homogeneity (suggestive of tumor necrosis) but ended treatment after 3 months due to hypothyroidism and GI toxicity, namely diarrhea. Within just 1 week of discontinuation, she had a concerning increase of 17% in her lesion. Thereafter, she has relapsed multiply but remains alive 18 months after discontinuing pazopanib. Conclusion: Despite the positive response seen to pazopanib, it’s toxicity profile can be over bearing for patients. In a retrospective analysis by Velho et al, a study involving 113 patients treated with pazopanib resulted in about 12% of those discontinuing treatment due to fatigue, diarrhea, and nausea/vomiting. In another study, described by Umeda et al, 3 patients with relapsed osteosarcoma who were treated with pazopanib were all alive at 21 months or longer. Of those, two discontinued treatment despite positive response due to nausea/fatigue, lymphopenia, anemia, hypothyroidism, and elevated alkaline phosphatase. Our experience as well of those as others suggests that pazopanib may have a role in prolonging survival among patients with osteosarcoma, however the extent of the side effects has clearly contributed to a lesser than optimal length of treatment.