Association between Severe Gastrointestinal Toxicity and Molecular Targeted Therapy in Patients Received Radiotherapy for Metastatic Bone Tumor or Myeloma

Abstract

Purpose of this study is to examine the association between severe gastrointestinal (GI) toxicity and molecular targeted therapy in patients received radiotherapy (RT) for bone lesions. This study included the patients who received RT for metastatic bone tumor or myeloma of abdominopelvic region between 2013 and 2014 at 6 institutions. Patient/tumor characteristics, RT dose, molecular targeted therapy, chemotherapy and GI toxicities were analyzed. GI toxicity was graded according to the CTCAE v4.0. Fisher’s exact test was used to examine the statistical significance. In total, 403 patients were included. Follow-up period was median 168 days (1-1798). Previous abdominopelvic surgery was performed in 145 patients. RT regimens were various, and major regimens were 30 Gy in 10 fractions and 20 Gy in 5 fractions. Total 21 different molecular targeted agents were administered in 185 patients. Vascular epidermal growth factor inhibitor (VEGFI) was administered in 85 patients; bevacizumab, sorafenib, axitinib, sunitinib, pazopanib, ramucirumab and regorafenib in 41, 24, 9, 13, 5, 1 and 2 patients. There were 30 (7.4%) patients who suffered ≥grade (G) 2 GI toxicities. G2, 3, 4 and 5 toxicities were observed in 15 (3.7%), 7 (1.7%), 4 (1.0%) and 4 (1.0%) patients, respectively. Duration between the beginning of RT and occurrence of GI toxicities was median 48.5 days (1-999 days). Perforation, bleeding, obstruction, diarrhea, gastroenteritis, vomiting and esophagitis were observed in 5 (1.2%), 7 (1.7%), 8 (2.0%), 4 (1.0%), 2 (0.5%), 1 (0.25%) and 3 (0.74%) patients, respectively. Among patients received molecular targeted therapy, there were in 3 (1.6%), 3 (1.6%), 4 (2.2%), 2 (1.1%), 3 (1.6%), 0 and 2 (1.1%) patients, respectively. Use of molecular targeted agents and use of VEGFIs showed no significant difference in occurrence of ≥G3 toxicities (3.8% vs 3.7%, p=1.0, and 7.2% vs 2.8%, p=0.095). History of previous abdominopelvic surgery (6.9% vs 1.6%, p=0.009) was only a significant factor. Among patients with molecular targeted agents use, ≥G3 toxicities in patients with VEGFIs use were significantly more than those in patients with other agents use (7.2% vs 1.0%, p=0.046). Moreover, among patients with VEGFIs use, ≥G3 toxicities in patients with VEGFIs use concurrently or during 7 days before and after RT were significantly more than those in patients with VEGFIs use during other period (18.2% vs 3.3%, p=0.04). Previous abdominopelvic surgery showed significantly higher occurrence rate of severe GI toxicities. Combination of RT with VEGFIs was significantly riskier than with the other agents. Use of VEGFIs concurrently or during 7 days before and after RT seems to be avoided.