Gastrointestinal Perforation and Cancer Therapy: Managing Risk to Achieve Benefit

Accessible online at: www.karger.com/onk Fax +49 761 4 52 07 14 E-mail Information@Karger.de www.karger.com Chemotherapy-associated colon toxicity has been described for most classes of cytotoxic agents currently used in the treatment of malignancy: it is usually manageable, rarely lifethreatening, and considered an acceptable risk. The gastrointestinal mucosa with its high turnover rate is particularly susceptible to cytotoxic damage, but the clinical manifestations for a particular agent vary and reflect great inter-patient pharmacodynamic differences, ranging from the more common and readily managed change in bowel movement frequency to the less common and more dangerous profuse watery diarrhea. These complications and the subsequent risks to the patient can be confounded by other factors. For example, typhilitis (neutropenic enterocolitis) has been recognized as one of the more life-threatening complications of chemotherapy and has been attributed to cytotoxic chemotherapy-induced gastrointestinal mucosa damage during prolonged periods of absolute neutropenia. Yet, with a greater awareness of this complication’s presenting signs and symptoms, and the improved sensitivity of computerized axial tomography to identify the intra-mucosal changes associated with typhilitis, a prompt and accurate diagnosis can be made and the appropriate intervention taken. Recently, two randomized trials of bevacizumab (rumbaVEGF, Avastin®, Roche, Basel, Switzerland) in colorectal cancer suggest an association of that agent with gastrointestinal perforation. In these two studies, the event rate appears to be between 1.1–1.5% of patients treated with the agent [2, 3]. And while death did occur in these studies it was usually due to sepsis, suggesting a delay in establishing a diagnosis of perforation, or because a corrective intervention was not sought [2]. With the growing clinical experience supporting the use of bevacizumab in the management of colorectal cancer, the need for a fuller understanding of the mechanisms behind this unusual complication is only surpassed in importance by the need for cancer specialists to develop an awareness of the The practice of medical oncology, more than any other subspecialty of internal medicine, is the practice of risk management. Our commonly used therapies, by and large, are indiscriminant in their targets; with most having preferential but not exclusive cytotoxic effects in malignant cells we must always carefully balance the expected benefit of treatment for our patients against the anticipated risks. In fact, it is difficult to identify any other field of medicine in which the routinely used therapeutic interventions carry the degree of risk that medical oncologists view as acceptable in that risk-benefit analysis. This analysis, however, is not limited to our generalized assessment of a treatment’s efficacy for a particular stage of disease, but occurs on a cycle-by-cycle basis for each patient we treat. A great part of our ability to accept such risk, and our patient’s willingness to do so as well, is the fact that we are trained to manage these risks, diminishing their significance and providing for the net effect of therapy to be a beneficial one. This ability to balance benefit with risk for therapies with narrow therapeutic indices requires not only the experiential facility to manage common side effects, but also an awareness of the uncommon, infrequently managed, and potentially lethal complications of therapy. In the current issue of ONKOLOGIE, Colucci and colleagues describe a case of cecal perforation in an individual who had been treated with 4 cycles of chemotherapy for esophageal adenocarcinoma [1]. Anecdotally, gastrointestinal perforation has been reported as a complication of chemotherapy, but usually in the setting of neutropenic enterocolits. What distinguishes this case report from most others is that the perforation did not occur in the setting of neutropenia and lacked the classic features of a typhilitis. And while it may be unusual in these pages for a case report to merit an editorial, doing so in this instance provides the means of improving awareness of a treatment-associated risk that we can expect to encounter more frequently. Gastrointestinal Perforation and Cancer Therapy: Managing Risk to Achieve Benefit