pazopanib and Retroperitoneal-Neoplasms

A 68-year-old man underwent an inguinal orchiectomy for a right testicular tumor and the pathological diagnosis was atypical lipomatous tumor. Nine years later, a resection procedure was performed for local recurrence. Five years after that second surgery, abdominal computed tomography (CT) findings revealed a low density mass 40 mm in size on the back side of the right kidney and enlarged fat in the retroperitoneal space. We performed a laparoscopic tumor resection under a diagnosis of lipoma or liposarcoma recurrence, and the pathological diagnosis was well differentiated liposarcoma. Treatment with pazopanib was started, as a CT examination showed that the tumor remained, after which we performed an open nephroureterectomy and resected the remaining tumor portion. Pazopanib treatment was continued and no obvious signs of recurrence were seen at 8 months after the most recent surgery. Although well differentiated liposarcoma usually recurs in the original tumor region, multicentric recurrence in other parts is possible.

Topics: Aged; Angiogenesis Inhibitors; Chemotherapy, Adjuvant; Humans; Indazoles; Liposarcoma; Male; Orchiectomy; Pyrimidines; Recurrence; Retroperitoneal Neoplasms; Sulfonamides; Testicular Neoplasms; Time Factors; Tomography, X-Ray Computed

Pazopanib is a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) that inhibits the vascular endothelial growth factor receptor A pathway and has the potential to cause ischaemic bowel changes, including perforation. Here we report a case of a 51-year-old man with large, metastatic, retroperitoneal leiomyosarcoma that developed a tumour-bowel fistula after 4 weeks of pazopanib therapy. He presented to the emergency department with sepsis and 1-week history of worsening fever, chills, nausea and diarrhoea. Abdominal CT findings of mesenteric and portal vein gas, commonly found in mesenteric ischaemia and VEGFR modulator-induced bowel toxicity, provided evidence for the causal relation. Unfortunately, the case was not amenable to surgery and patient succumbed to the illness.

Topics: Angiogenesis Inhibitors; Diagnosis, Differential; Humans; Indazoles; Intestinal Fistula; Intestinal Perforation; Leiomyosarcoma; Male; Middle Aged; Pyrimidines; Retroperitoneal Neoplasms; Sulfonamides; Tomography, X-Ray Computed

Pazopanib was administered to a 44-year-old man with local recurrence of retroperitoneal liposarcoma. Computed tomography showed an intestinal edema, which gradually progressed 15 months after pazopanib administration although he had no clinical symptoms. Upper gastrointestinal endoscopy implicated marked edematous hypertrophy of the Kerkling's fold. Pathological findings showed crystal deposition and fat accumulation, without a malignant component. All these abnormal findings resolved after pazopanib discontinuation.

Topics: Adult; Antineoplastic Agents; Edema; Endoscopy, Gastrointestinal; Humans; Indazoles; Intestinal Diseases; Intestinal Mucosa; Kidney Neoplasms; Liposarcoma; Male; Neoplasm Recurrence, Local; Pyrimidines; Retroperitoneal Neoplasms; Sulfonamides; Tomography, X-Ray Computed

Topics: Angiogenesis Inhibitors; Biopsy; Humans; Indazoles; Male; Middle Aged; Paraganglioma; Pyrimidines; Retroperitoneal Neoplasms; Sulfonamides; Tomography, X-Ray Computed; Treatment Outcome

The patient(woman, approximately 46 years old)began pazopanib (PAZ) treatment (800 mg/day)f ollowing the recurrence of retroperitoneal leiomyosarcoma. Prior to treatment, the patient's platelet count was 18.6×10(4)/µl and her neutrophil count was 1.61×10(3)/µl . The platelet count decreased to 9.2×10(4)/µl on day 7 and to 5.4×10(4)/µl on day 21 after commencement of treatment. The neutrophil count was 0.97×10(3)/µl on day 28 and 0.68×10(3)/µl on day 35 after commencement of treatment. Thus, PAZ treatment was stopped on day 35. The blood sampling results on day 42 after commencement of treatment showed that the platelet count was 13.0×10(4)/µl and that the neutrophil count had recovered to 1.28×10(3)/µl . At that time, PAZ treatment was resumed at a reduced dose of 600 mg/day. By day 84 after commencement of treatment, the platelet count had increased from 12.7 to 13.8×10(4)/µl and the neutrophil count had increased from 1.02 to 1.34×10(3)/µl ; treatment was subsequently continued. The main adverse effects that have been reported for PAZ are hypertension and frequent liver dysfunction; these reports also indicate that the incidence of severe cytopenia(thrombocytopenia, neutropenia)is quite low. However, our patient exhibited cytopenia after commencement of PAZ treatment and her blood cell counts recovered once treatment was ceased, independent of other possible medications. Our findings suggest that cytopenia should be considered as an adverse effect of PAZ.

Topics: Angiogenesis Inducing Agents; Female; Humans; Indazoles; Leiomyosarcoma; Middle Aged; Neutropenia; Pyrimidines; Recurrence; Retroperitoneal Neoplasms; Sulfonamides; Thrombocytopenia

Pazopanib, a novel tyrosine kinase inhibitor, is an effective therapeutic agent for patients with advanced soft tissue sarcoma. Here we report three patients with recurrent retroperitoneal liposarcoma who were treated with pazopanib. Case 1: A 54-year-old male received three courses of combined chemotherapy consisting of doxorubicin and ifosfamide for recurrent left retroperitoneal dedifferentiated liposarcoma and liver metastasis following tumor excision. Because of the lack of response to chemotherapy, 400 mg/day of pazopanib was subsequently administered for two weeks. The patient died 3 weeks after the initiation of pazopznib therapy. Case 2: A 78-year-old male with right retroperitoneal dedifferentiated liposarcoma underwent irradiation for a recurrent tumor 16 months after the initial tumor excision. Pazopanib (600 mg/day) was partially effective for 2 months. Pazopanib was administered for 7 months, but the patient died 8 months after the initiation of pazopanib therapy. Case 3 : An 80-year-old male with locally recurrent right retroperitoneal myxoid liposacroma was treated with 600 mg/day of pazopanib from 5 months after tumor excision. He remains alive and has had stable disease for 17 months to date. In conclusion, pazopanib may be effective in a subset of patients with recurrent retroperitoneal liposarcoma.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Humans; Indazoles; Liposarcoma; Male; Middle Aged; Neoplasm Staging; Pyrimidines; Recurrence; Retroperitoneal Neoplasms; Sulfonamides; Tomography, X-Ray Computed

Topics: Fatal Outcome; Humans; Indazoles; Male; Middle Aged; Neoplasm Recurrence, Local; Pyrimidines; Retroperitoneal Neoplasms; Sarcoma, Ewing; Sulfonamides