pazopanib and Sarcoma--Endometrial-Stromal

Long-term follow-up reports of low-grade endometrial stromal sarcoma (LGESS) including its clinical course and pathological data are rare. We previously reported the case of a Japanese woman diagnosed with LGESS, who was treated with multidisciplinary therapy. She had been suffering from uterine cervical tumor diagnosed as cervical polyps, or fibroid in statu nascendi, since 24 years old. The patient had survived for 25 years with the disease. This report presents her progress and pathological change since the previous report.. At age 45, the patient experienced a relapse of the remnant LGESS tumor between the right diaphragm and liver. Although chemotherapy was not effective, the tumor was eliminated by proton therapy. At age 46 years, the remnant tumors outside the irradiated field were resected. The disease was originally diagnosed as "neuroendocrine carcinoma (NEC)" using the surgical specimen. Therefore, cisplatin and irinotecan combination chemotherapy were administered to treat the remnant dissemination. After 4 cycles of chemotherapy, the liver metastases had enlarged and were resected surgically. Consequently, no remnant tumor was visible in the abdominal cavity at the end of the surgery. To determine the origin of NEC, we examined the previously resected specimens obtained from her ileum at age 40 years. A boundary between the LGESS and neuroendocrine tumor grade 2 (NET G2)-like lesion was found in the tumor, indicating that the origin of these tumors was LGESS. After less than 2 years of chemotherapy and undergoing surgery, a relapse of the tumor in the liver induced biliary duct obstruction with jaundice, which was treated with endoscopic retrograde biliary drainage. Although pazopanib prolonged her life for 10 months, she died from sepsis at age 49 years, which was caused by the infection that spread to the liver metastatic tumor via the stented biliary ducts. Autopsy revealed adenocarcinoma-like differentiation of the tumor.. This LGESS patient has survived for a long time owing to multidisciplinary treatment including proton therapy. The LGESS tumor differentiated to NET G2-like tissue and then further to adenocarcinoma-like tissue during the long-term follow-up.

Topics: Adult; Autopsy; Drainage; Endometrial Neoplasms; Fatal Outcome; Female; Humans; Indazoles; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Proton Therapy; Pyrimidines; Sarcoma, Endometrial Stromal; Sepsis; Sulfonamides; Young Adult

Pazopanib is an oral tyrosine kinase inhibitor registered for metastatic renal cell carcinoma and soft tissue sarcoma. Liver toxicity is a common side effect for this class of agents. The current opinion is that in case of severe liver toxicity pazopanib should be interrupted and restarted at a lower dose after returning to Common Terminology Criteria for Adverse Events (CTCAE) grade 1. After recurrence of liver toxicity at the lower dose it is advised to permanently stop pazopanib. We describe a patient with an YWHAE-FAM22 translocated endometrial stromal sarcoma with a remarkable response to pazopanib despite recurrent liver toxicity.. A 40 year old woman was diagnosed with metastatic YWHAE-FAM22 translocated endometrial stromal sarcoma. She was treated successively with doxorubicin, megestrol acetate and anastrozole, before pazopanib was initiated. Several dose interruptions and reductions were necessary due to liver toxicity, but nevertheless she had a good partial response. Seven months after the start, pazopanib was permanently stopped because of a bilateral pneumothorax. Nine months later it was reinitiated because of progression and was continued for another 8 months until final disease progression.. In contrast to the current summary of product characteristics of pazopanib, the drug was successfully continued despite recurrent liver toxicity, and no further liver function deterioration was found. This case suggests that further dose reductions are good practice when liver toxicity limits treatment in responding patients. Secondly, this patient with rare YWHAE-FAM22 translocated endometrial stromal sarcoma showed a remarkable response to VEGFR/KIT inhibitor pazopanib. Recently, it was reported that this specific subtype of endometrial stromal sarcoma overexpresses CD117, but has no KIT mutations. This case illustrates that (a) pazopanib can be continued in patients with recurrent liver toxicity after dose reductions under strict surveillance and that (b) pazopanib shows good efficacy in YWHAE-FAM22 translocated endometrial stromal sarcoma.

Topics: Adult; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Indazoles; Liver; Neoplasm Recurrence, Local; Pyrimidines; Sarcoma, Endometrial Stromal; Sulfonamides