Cynthia Liu1, Rajan Amin2, Anusha S Thomas3, Yinghong Wang4, Malek Shatila3, Nicholas Short5, Mehmet Altan6, Amishi Shah7, Omar Alhalabi7, Pablo Okhuysen8. 1. Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA. 2. Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA. 3. Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ywang59@mdanderson.org. 5. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 6. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 7. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 8. Department of Infectious Disease, Infection Control and Employment Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract
PURPOSE: A variety of tyrosine kinase inhibitors (TKIs) are currently approved for the treatment of solid tumors and hematological cancers. However, TKIs are often associated with gastrointestinal (GI) adverse effects (AEs), especially diarrhea. Therefore, in the present study, we aimed to describe the clinical features and outcomes of TKI-associated lower GI AEs. METHODS: This was a retrospective single-center cohort study of patients with cancer treated with TKIs from March 2016 to September 2020 who experienced diarrhea without other identifiable causes. Basic and GI AE-related characteristics and outcomes were compared using χ2 and Mann-Whitney U tests. RESULTS: Of 2172 patients who received TKIs over the study period, we included 228 in the final analysis. Of these, 166 (72.8%) had hematological cancers. Besides diarrhea, GI symptoms included nausea (36.4%), vomiting (21.9%), abdominal pain (15.4%), and bleeding (3.1%). Symptoms were typically mild, with 209 patients (91.7%) presenting with Common Terminology Criteria for Adverse Events grade 1-2 diarrhea. Only 5 patients (2.2%) received immunosuppressants for diarrhea treatment, 83 (36.4%) received no treatment, 29 (12.7%) received antibiotics, 101 (44.3%) received supportive antidiarrheal medications, and 17 patients (7.5%) needed TKI dose reduction or cessation of TKI use. When compared with patients with hematological cancers, those with solid tumors had a higher rate of hospitalization (29.0% vs. 7.2%; p < 0.001) and mortality (75.8% vs. 43.4%; p < 0.001) but a lower rate of recurrence of GI AEs (21.0% vs. 42.8%; p = 0.003. Only 15 patients (6.6%) underwent colonoscopy, with normal endoscopic findings in 8 patients (53.3%) and nonulcerative inflammation in 5 patients (33.3%). The inflammation universally involved the left colon. Twelve of the 15 patients who underwent colonoscopy had active colitis. In the hematological cancer group, patients with acute myeloid leukemia had a lower GI AE recurrence rate than did patients with other hematological cancers (7.2% vs. 30.1%; p = 0.001). CONCLUSION: Ten percent of cancer patients receiving TKIs experienced lower GI AEs, which were usually mild. Symptoms TKI-related GI adverse effects were nonspecific, often overlapping those of other cancer therapy-related GI AEs. Treatment of GI AEs was largely supportive, with limited roles for antibiotics and immunosuppressants.
PURPOSE: A variety of tyrosine kinase inhibitors (TKIs) are currently approved for the treatment of solid tumors and hematological cancers. However, TKIs are often associated with gastrointestinal (GI) adverse effects (AEs), especially diarrhea. Therefore, in the present study, we aimed to describe the clinical features and outcomes of TKI-associated lower GI AEs. METHODS: This was a retrospective single-center cohort study of patients with cancer treated with TKIs from March 2016 to September 2020 who experienced diarrhea without other identifiable causes. Basic and GI AE-related characteristics and outcomes were compared using χ2 and Mann-Whitney U tests. RESULTS: Of 2172 patients who received TKIs over the study period, we included 228 in the final analysis. Of these, 166 (72.8%) had hematological cancers. Besides diarrhea, GI symptoms included nausea (36.4%), vomiting (21.9%), abdominal pain (15.4%), and bleeding (3.1%). Symptoms were typically mild, with 209 patients (91.7%) presenting with Common Terminology Criteria for Adverse Events grade 1-2 diarrhea. Only 5 patients (2.2%) received immunosuppressants for diarrhea treatment, 83 (36.4%) received no treatment, 29 (12.7%) received antibiotics, 101 (44.3%) received supportive antidiarrheal medications, and 17 patients (7.5%) needed TKI dose reduction or cessation of TKI use. When compared with patients with hematological cancers, those with solid tumors had a higher rate of hospitalization (29.0% vs. 7.2%; p < 0.001) and mortality (75.8% vs. 43.4%; p < 0.001) but a lower rate of recurrence of GI AEs (21.0% vs. 42.8%; p = 0.003. Only 15 patients (6.6%) underwent colonoscopy, with normal endoscopic findings in 8 patients (53.3%) and nonulcerative inflammation in 5 patients (33.3%). The inflammation universally involved the left colon. Twelve of the 15 patients who underwent colonoscopy had active colitis. In the hematological cancer group, patients with acute myeloid leukemia had a lower GI AE recurrence rate than did patients with other hematological cancers (7.2% vs. 30.1%; p = 0.001). CONCLUSION: Ten percent of cancer patients receiving TKIs experienced lower GI AEs, which were usually mild. Symptoms TKI-related GI adverse effects were nonspecific, often overlapping those of other cancer therapy-related GI AEs. Treatment of GI AEs was largely supportive, with limited roles for antibiotics and immunosuppressants.
Authors: Thomas W Flaig; Fernando J Kim; Francisco G La Rosa; Kathryn Breaker; Jonathan Schoen; Paul D Russ Journal: Invest New Drugs Date: 2008-06-18 Impact factor: 3.850
Authors: Eric B Haura; Tawee Tanvetyanon; Alberto Chiappori; Charles Williams; George Simon; Scott Antonia; Jhanelle Gray; Sharon Litschauer; Leticia Tetteh; Anthony Neuger; Lanxi Song; Bhupendra Rawal; Michael J Schell; Gerold Bepler Journal: J Clin Oncol Date: 2010-02-08 Impact factor: 44.544
Authors: Rossella Elisei; Martin J Schlumberger; Stefan P Müller; Patrick Schöffski; Marcia S Brose; Manisha H Shah; Lisa Licitra; Barbara Jarzab; Viktor Medvedev; Michael C Kreissl; Bruno Niederle; Ezra E W Cohen; Lori J Wirth; Haythem Ali; Colin Hessel; Yifah Yaron; Douglas Ball; Barry Nelkin; Steven I Sherman Journal: J Clin Oncol Date: 2013-09-03 Impact factor: 44.544
Authors: Marye J Boers-Sonderen; Sasja F Mulder; Iris D Nagtegaal; Lauranne A A P Derikx; Geert J A Wanten; Peter F A Mulders; Winette T A van der Graaf; Frank Hoentjen; Carla M L van Herpen Journal: Acta Oncol Date: 2016 Impact factor: 4.089
Authors: George D Demetri; Margaret von Mehren; Charles D Blanke; Annick D Van den Abbeele; Burton Eisenberg; Peter J Roberts; Michael C Heinrich; David A Tuveson; Samuel Singer; Milos Janicek; Jonathan A Fletcher; Stuart G Silverman; Sandra L Silberman; Renaud Capdeville; Beate Kiese; Bin Peng; Sasa Dimitrijevic; Brian J Druker; Christopher Corless; Christopher D M Fletcher; Heikki Joensuu Journal: N Engl J Med Date: 2002-08-15 Impact factor: 91.245
Authors: Axel Grothey; Eric Van Cutsem; Alberto Sobrero; Salvatore Siena; Alfredo Falcone; Marc Ychou; Yves Humblet; Olivier Bouché; Laurent Mineur; Carlo Barone; Antoine Adenis; Josep Tabernero; Takayuki Yoshino; Heinz-Josef Lenz; Richard M Goldberg; Daniel J Sargent; Frank Cihon; Lisa Cupit; Andrea Wagner; Dirk Laurent Journal: Lancet Date: 2012-11-22 Impact factor: 79.321