Cancer agents have the potential for severe, and occasionally fatal, adverse drug events. Many receive accelerated approval for use after small clinical trials, with adverse drug events being identified after further experience in the postmarketing clinical setting.1 Moreover, chemotherapy risks may be especially high in tertiary care settings whose patients frequently are subject to complex treatment protocols with high dosages, novel agents, or novel combinations of agents. The case of Betsy Lehman at the Dana-Farber Cancer Institute is a dramatic example of these risks. In 1994, as a participant in a clinical trial investigating a nonstandard schedule of cyclophosphamide, she received a fatal overdose. Multiple system failures allowed the erroneous order to propagate over the course of 4 days.2

Six years after this tragic event, Gandhi et al. conducted a broad survey of medication errors at the Dana-Farber Cancer Institute.3 They examined more than 10,000 medication orders and identified 306 errors. The estimated ratio of 31 errors per 1000 orders is similar to that found in medical-surgical inpatient and primary care outpatient settings. The most frequent potential adverse drug events noted among the pharmacy orders for adult cancer patients were due to the omission of chemotherapy dosages (5.9 per 1000 orders) and withholding treatment without discontinuing the corresponding order in the computerized physician order entry system (5.0 per 1000 orders). Among pediatric cancer patients, for whom a paper-based ordering system was used, the most frequent potential adverse drug events were the result of orders not being discontinued and the wrong dosage of a medication being prescribed, at a rate of 4.3 per 1000 orders each. Fortunately, pharmacists and nurses intercepted nearly half of all potential adverse drug events before the orders were carried out, and no error resulted in harm to the patient. After the findings of the study by Gandhi et al. were reported to officials at the Dana-Farber Cancer Institute, several system changes were implemented. These changes included the implementation of a new adult chemotherapy computerized order entry system that includes embedded templates with standardized chemotherapy regimens, ancillary premedications, and hydration orders.

The study by Gandhi et al. adds to a growing international effort to implement innovative computerized solutions for safer cancer chemotherapy (Table 1). A computerized system for ordering ambulatory chemotherapy has been implemented provincewide in Ontario, Canada.4 This system incorporates many of the improvements outlined in the article by Gandhi et al.,3 including the use of standardized templates and drug interaction checking in computerized physician order entry systems. It also adds improvements that facilitate communication between nurses and physicians regarding order changes. In the U.K., a national computerized system currently is being developed to provide normative feedback to prescribers of chemotherapy in an attempt to reduce regional variations in the selection of chemotherapy regimens.5

Table 1. Strategies for Improving Safety in the Setting of Ambulatory Chemotherapy
TargetExamples of strategies
Prevention of medication errorsIntegrating communications regarding holding and discontinuing orders into the ordering documentation process.
 Computerized order managements such as templating orders, guiding and checking doses, and tracking the monitoring of adverse events.
Prevention of adverse drug events related to patient and drug factorsPatient-tailored, standardized treatment protocols.
Integrating pharmacogenomics and other patient factors into clinical decision rules to guide chemotherapy.
 Improved patient education and participation in protocol selection.
Early recognition and treatment of adverse drug events related to patient and drug factorsClinically based, hypothesis-driven pharmacovigilance through collaborations of cancer centers. Computerized surveillance of the electronic medical record for indications of incipient adverse drug reactions.13

However, lessons learned from adopting computerized physician order entry systems to the general medical setting are likely to be applicable to the oncology setting. Tertiary care centers in Boston, Philadelphia, and Salt Lake City have found that the implementation of computerized order entry systems resulted in unforeseen medication errors and adverse drug events.6, 7 For example, although standardized templates facilitated the electronic ordering of chemotherapy regimens at a tertiary care hospital in Salt Lake City, the drugs could not be displayed according to the administration sequence. Because the display could not be modified locally, coded order entry was replaced with a safer free-text approach for chemotherapy. Moreover, extensive computerization of inpatient medication processes at the same hospital was found to not address the most troublesome aspects of medication ordering and monitoring.8

Other approaches that target patient and drug factors also may help to prevent adverse drug events.8, 9 Pharmacogenomic tests can help physicians choose chemotherapeutic agents that beneficially affect the likelihood of adverse drug reactions and/or tumor response.10 Clinical decision rules, possibly including pharmacogenomics, can be developed to guide ordering and monitoring.8, 11 Clinicians and patients generally have more information regarding the quantity rather than the quality of life associated with chemotherapy regimens. Improved knowledge and communication of quality versus quantity of life information may lead to the selection of regimens with fewer adverse reactions.

Efforts to facilitate the early recognition and treatment of adverse drug events in patients undergoing chemotherapy also have proven to be helpful. Collaborations among clinicians at National Cancer Institute (NCI)-designated comprehensive cancer centers have led to the timely identification and reporting of serious and previously unrecognized adverse drug events. For example, the Dana-Farber Cancer Institute, the Robert H. Lurie Comprehensive Cancer Center, and the M. D. Anderson Cancer Center with investigators affiliated with the Research And Reports on Adverse Reactions (RADAR) project (a recently initiated pharmacovigilance effort) have reported serious and previously unrecognized adverse drug events that occurred when “correct dosages” of cancer therapies were administered “correctly” to cancer patients. These clinical events included thalidomide-associated thromboembolism when patients with multiple myeloma received concomitant therapy with doxorubicin or dexamethasone, gemcitabine-associated interstitial pneumonitis, or sinusoidal obstructive syndrome when younger patients with acute myelogenous leukemia underwent an allogeneic stem cell transplantation shortly after therapy with gemtuzumab.12 The report by Gandhi et al. extends the range of potential benefits that can be derived from conducting pharmaceutical safety studies at NCI-designated comprehensive cancer centers in which collaborations exist among pediatric and adult oncologists and investigators with expertise in statistical analysis, operations research, and clinical informatics.3

The report by Gandhi et al.3 represents an important step in implementing computerized solutions and other system changes that are designed to improve pharmaceutical safety in the ambulatory oncology setting. We look forward to reviewing additional reports that describe the benefits and drawbacks of these changes.


  1. Top of page