The study was approved by Ethics Committee of Ji’nan Central Hospital Affiliated to Shandong University and written informed consent was obtained from patient. Apatinib started to be taken orally 425 mg per day from February 15, 2016. One week later, the symptoms of abdominal distension, nausea, and vomiting were gradually alleviated. The PS score reduced to 3. Then, reviewed through CT scan, we found tumor slightly shrank and the inner liquid-density area was enlarged, which was considered as necrosis. This case was evaluated as partial remission (PR) (Fig. 1C). However, in the course of taking apatinib, the patients suffered hypertension, and the highest blood pressure was 170/110 mm Hg. We controlled blood pressure by antihypertensive drug. Valsartan (a type I angiotensin II receptor antagonist) 80 mg once a day was used. Three days later, blood pressure dropped to 130/80 mm Hg. After 2 months of follow-up, the disease of the patient was stable, but she presented grade 3 hand–foot syndrome (HFS) with the hand and foot blister and perianal ulcers. Apatinib was reduced to 250 mg per day and moisturizing ointment was used. After 1 week, HFS of the patient fell to grade 2. This patient stopped oral apatinib on May 6 because of aphagia and died on May 18, 2016.
In this case, the drugs we used included docetaxel, gemcitabine, and cisplatin, but all were invalid. The use of apatinib achieved a 3-month PFS.
Conventional chemotherapy is of low efficiency, so new drugs and target therapy might be good options. For example, eribulin and pazopanib are new treatment options for the patients with metastatic STS.[11,12] Eribulin mesylate was reported to have selective activity in LPS. However, the adverse effects of eribulin were severe. In a phase III trial, treatment emergent adverse events occurred in 224 (99%) of 226 patients who received eribulin. Grade 3/4 adverse events were 152 (67%) who received eribulin. The Food and Drug Administration (FDA) approved pazopanib as second-line chemotherapy for the treatment of patients with advanced nonlipogenic STS, but still not yet for LPS. In addition, eribulin and pazopanib have not been approved for clinical use in China.
A majority of STS have been discovered to have the high expression level of proangiogenic growth factors that contribute tumor angiogenesis, growth, and progression. VEGF expression was observed in 68% of PLS, and microvessel density was especially higher in liposarcoma, which are effective indicators of antiangiogenic drugs. Meanwhile, antiangiogenic targeted drugs such as sunitinib, sorafenib, and pazopanib all appeared to demonstrate acceptable antitumor activity in liposarcomas.[15–17] Moreover, several articles reported that apatinib had a good effect in angiosarcoma and round cell liposarcoma. Furthermore, owing to old age and poor PS, the patient could not tolerate to continue chemotherapy. Therefore, apatinib monotherapy was then used to control the disease.
Although obtained some experience in this case, we should have more explorations in terms of treatment options. For example, combination approaches, such as apatinib combined with radiotherapy or tyrosine kinase inhibitor (TKI) or cyclin-dependent kinases (CDK) inhibitors, may be an attractive potential therapy paradigms. Besides, to find biomarkers to predict drug efficacy is also one of the challenges with antiangiogenic inhibitors such as apatinib. A study of biomarkers in breast cancer patients treated with apatinib showed that hypertension was independent predictive factors for improved PFS and clinical benefit rate. Predictive biomarkers could discriminate patients who are most likely to be sensitive to apatinib and avoid exposure to useless toxic medicine. Thus, additional studies on biomarkers may be useful in predicting personalized therapeutic response.
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