Shreyaskumar R. Patel, MD: Standard of Care for Invasive, Unresectable Leiomyosarcoma

What is the current standard of care for patients with invasive, unresectable leiomyosarcoma?

Like in most situations where the tumor is either advanced and unresectable, or metastatic like this case, the standard of care would be systemic therapy. As much as medical professionals want the field to move into targeted therapies directed at specific subsets of patients, conventional chemotherapy remains the standard of care. Giving this patient gemcitabine and docetaxel is a reasonable approach. There is evidence that the combination is just as active as other regimens in patients with gynecological leiomyosarcomas. For the other sites, I think the combination would be a reasonable choice.

Whether treatment starts with one regimen or another depends on several factors. Some of those factors are related to the origin of the tumor. Ifosfamide is not very active for non-uterine leiomyosarcoma, so as you see in this patient after gemcitabine and docetaxel they received doxorubicin and dacarbazine, which has activity in leiomyosarcomas. Several other factors should go into the decision-making as well, such as the patient's performance status, patient's lifestyle, and how they wish to carry on with their day-to-day routine, because the side-effect profiles are clearly different.

In general terms, I think systemic therapy would be the standard of care here. Chemotherapy is the mainstay of systemic therapy, and the top two regimens used are gemcitabine and docetaxel or an anthracycline-based regimen.

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