Strategies for the targeted delivery of therapeutics for osteosarcoma

Abstract

Background: Conventional therapy for osteosarcoma has reached a plateau of 60 - 70%, a 5-year survival rate that has changed little in two decades, highlighting the need for new approaches.

Objective: To review the alternative means of delivering effective therapy for osteosarcoma that reach beyond the central venous catheter.

Methods: Drawing on the author's own experiences providing care to high-risk osteosarcoma patients and reviewing the last two decades of literature describing sarcoma therapy, available information is summarized about potential osteosarcoma treatments that deliver therapy by a less conventional route.

Results/conclusions: Intra-arterial chemotherapy has a limited impact on survival, but may help to achieve a better limb salvage. Intrapleural chemotherapy is important for managing malignant effusions. The development of inhalation therapies, treatments that target new bone formation such as bisphosphonates, chemically targeted radiation and antibody-based therapies all have potential to improve osteosarcoma therapy.

Figure 1

Arteriograms from an osteosarcoma patient before and after receiving intra-arterial cisplatin. A patient with right distal femur osteosarcoma was treated with four courses of intra-arterial cisplatin (120 mg/M2 infused over 4 hours per cycle) together with systemic doxorubicin (90 mg/M2 iv). The upper panels show the pre-treatment arteriograms, while the lower panels show the arteriograms obtained after three courses of therapy, concurrent with placement of the intra-arterial catheter for his fourth cycle. In the upper left panel, a soft tissue mass (white arrow) is clearly visible, deforming the femoral artery. In the upper right panel, with the bone image digitally subtracted, the vascular blush of abnormal tumor blood supply is clearly seen (black arrows). In the lower images, the deformation of the femoral artery from the soft tissue mass is completely resovled (white arrow), and the abnormal tumor blood vessels that cause the vascular blush are now eliminated.

Figure 2

Bone scan with ⁹⁹Tc and scan of therapeutic ¹⁵³Sm from the same patient. Left panel: A teenager with small-cell osteosarcoma of the right distal femur and widely metastatic disease had a bone scan after receiving four courses of doxorubicin (90 mg/M2) and ifosfamide (9 gm/M2). The radiotracer filling the bladder is clearly seen, as is the abnormal uptake in the right distal femur. Right panel: Following six weeks of external beam radiotherapy (60 Gr total dose), augmented with cisplatin (60 mg/M2 per dose on two consecutive weeks) and high-dose methotrexate (12 gm/M2 given in week four), she was treated with Samarium-153 Ethylene Diamine Tetramethylene Phosphonate (1 mCi/kg) on the penultimate day of external beam radiotherapy. The image shown was taken 24 hours after samarium infusion. Tracer signal is decreased in the primary tumor, consistent with a treatment effect during external beam radiotherapy. We administered gemcitabine after the final dose of external beam radiation was delivered. The visibility of normal bones on the samarium scan provides an explanation for the sometimes prolonged marrow suppression observed following samarium treatment.