Jonathan C. Trent, MD, PhD: Targeted Therapies Influencing Treatment Options

Would you consider additional chemotherapy in this patient?

Patients with leiomyosarcoma are often treated with targeted therapies. One of the major therapies that we use is pazopanib. Pazopanib is a multi-targeted tyrosine kinase inhibitor (TKI) that targets KIT, VEGF receptors, and PDGF receptors. A newer agent called trabectedin targets the minor groove of DNA, and it's thought to interfere with the transcription of certain factors that interfere with the tumor cell phenotype.

CASE: Soft-Tissue Sarcoma (Part 1)

Rachel F is a 58-year-old school teacher from Roanoke, Virginia. Her medical history is notable for mild hypertension and total knee replacement in 2011

• In March of 2013, she presented to her PCP with abdominal fullness and distension of several months’ duration; physical exam showed mild abdominal discomfort on palpation; she denied any recent weight loss
• Initial abdominal sonography was inconclusive; subsequent CT scan showed a heterogeneously enhancing retroperitoneal mass along segment I of the inferior vena cava (IVC) and central necrosis
• She underwent contrast-enhanced CT with coronal and sagittal reconstructions, which showed encasement of the aorta and multiple hepatic metastases
• CT guided biopsy of the mass showed leiomyosarcoma that was immunohistochemically positive for desmin, smooth muscle actin, and vimentin, with a high proliferative rate (Ki67 > 60%)
• She underwent chemotherapy with gemcitabine and docetaxel for a total of 6 cycles, and experienced a minor response. Therapy was discontinued however, in November 2013 due to cumulative toxicity

Follow-up CT scan in January 2014 showed progression at multiple sites; at the time of follow up, her ECOG performance status was 1, with renal and hepatic function within normal limits

• She underwent six cycles of chemotherapy with anthracycline and dacarbazine, and her disease stabilized

In September of 2014 she returns for follow-up, unable to work with increasing fatigue and abdominal pain, and her CT scan was consistent with progressive disease

• She received treatment with pazopanib at 800 mg daily for metastatic disease
• Patient tolerated the treatment well, with mild fatigue and diarrhea, and her symptoms improved

After 4 months of therapy, she presents with worsening abdominal pain and declining performance status

• CT showed extensive progression of the primary tumor and hepatic metastases
• At progression, CBC, liver, and renal function were within normal limits, ECOG performance status was 2