Journal Article10.1007/S00280-019-03928-W
A pilot study of first-line olaratumab, doxorubicin and ifosfamide in patients with metastatic soft tissue sarcoma.
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TL;DR: According to the preliminary experience, adding olaratumab to doxorubicin and ifosfamide is active and its safety profile is comparable to that of dox orubic in and ifOSfamide alone in MSTS.
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Abstract: Olaratumab (O) is a monoclonal antibody that specifically binds PDGFRα. The addition of O to doxorubicin (D) has been approved by the regulatory authorities for metastatic soft tissue sarcoma (MSTS). Since the combination of D + ifosfamide (I) is commonly used in MSTS and is associated with a higher response rate than D alone, it seems reasonable to combine O with the combination of D + I (ODI). We report our preliminary experience with O + D+I in MSTS. Between 01/01/2015 and 30/05/2018, 15 patients (pts) with MSTS were treated with ODI as first-line therapy. The treatment protocol consisted of IV D 50 mg/m2 and I 5000 mg/m2, day 1 (3 pts), or D 37.5 mg/m2 and I 3000 mg/m2 days 1–2 (12 pts). O (15 mg/kg) was given IV on days 1, 8, and cycles were repeated every 21 days. With a median follow up of 16 months, 63 cycles of ODI were given. Objective response was achieved in 4 pts (27%) (CR in 3, PR in 1); 5 pts (33%) remained with stable disease for ≥ 5 mo. Median overall survival was 22 months. Major hematological toxicities (grade 3–4) included: neutropenia—7 pts (47%), and neutropenic fever—3 pts (20%). Non-hematological toxicities included grade 3 diarrheas in 2 pts (13%) after the second cycle. There was no treatment-related mortality. According to our preliminary experience, adding olaratumab to doxorubicin and ifosfamide is active and its safety profile is comparable to that of doxorubicin and ifosfamide alone in MSTS.
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Citations
GZ17-6.02 and Doxorubicin Interact to Kill Sarcoma Cells via Autophagy and Death Receptor Signaling
TL;DR: It is concluded that 602 and doxorubicin interact to increase autophagosome formation and autophagic flux as well as causing elevated death receptor signaling resulting in mitochondrial dysfunction and tumor cell death.
Olaratumab's failure in soft tissue sarcoma.
TL;DR: The PDGFRα antagonist Olaratumab (Lartruvo) was withdrawn from the market due to disappointing results as discussed by the authors, leading to the development of a new class of soft tissue sarcomas.
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