pazopanib and Intestinal-Diseases

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

Gastrointestinal injury occurs rarely with agents that affect the vascular endothelial growth factor receptor and with abdominal stereotactic body radiation therapy (SBRT). We explored the incidence of serious bowel injury (SBI) in patients treated with SBRT with or without vascular endothelial growth factor inhibitor (VEGFI) therapy.. Seventy-six patients with 84 primary or metastatic intra-abdominal lesions underwent SBRT (median dose, 50 Gy in 5 fractions). Of the patients, 20 (26%) received VEGFI within 2 years after SBRT (bevacizumab, n=14; sorafenib, n=4; pazopanib, n=1; sunitinib, n=1). The incidence of SBI (Common Terminology Criteria for Adverse Events, version 4.0, grade 3-5 ulceration or perforation) after SBRT was obtained, and the relationship between SBI and VEGFI was examined.. In the combined population, 7 patients (9%) had SBI at a median of 4.6 months (range, 3-17 months) from SBRT. All 7 had received VEGFI before SBI and within 13 months of completing SBRT, and 5 received VEGFI within 3 months of SBRT. The 6-month estimate of SBI in the 26 patients receiving VEGFI within 3 months of SBRT was 38%. No SBIs were noted in the 63 patients not receiving VEGFI. The log-rank test showed a significant correlation between SBI and VEGFI within 3 months of SBRT (P=.0006) but not between SBI and radiation therapy bowel dose (P=.20).. The combination of SBRT and VEGFI results in a higher risk of SBI than would be expected with either treatment independently. Local therapies other than SBRT may be considered if a patient is likely to receive a VEGFI in the near future.

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Analysis of Variance; Antibodies, Monoclonal, Humanized; Bevacizumab; Duodenal Diseases; Humans; Indazoles; Indoles; Intestinal Diseases; Middle Aged; Niacinamide; Phenylurea Compounds; Pyrimidines; Pyrroles; Radiography; Radiosurgery; Radiotherapy Dosage; Receptors, Vascular Endothelial Growth Factor; Retrospective Studies; Sorafenib; Stomach Ulcer; Sulfonamides; Sunitinib; Ulcer