Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: Standard protocol effective in 57 patients for 255 courses☆
Introduction
Carboplatin, a platinum analogue, and paclitaxel, a taxane agent, are widely used in the treatment of gynecologic malignancies [1]. Results from randomized clinical trials have demonstrated the efficacy of platinum–taxane combination as the standard of care for most patients with ovarian cancer [2], [3]. Therefore, the ability to safely administer these agents provides significant clinical benefit for patients.
Patients treated with multiple courses of carboplatin experience increased rates of hypersensitivity reactions (HR) [4]. The incidence of reactions increases to 27% in patients receiving more than 7 cycles of carboplatin, with more than 50% of patients developing moderate to severe symptoms [5]. HR to paclitaxel occur in approximately 16–40% of patients while premedication with antihistamines and corticosteroids has decreased the incidence to less than 10% [6]. Symptoms of HR vary from cutaneous reactions such as flushing and urticaria to life-threatening respiratory and cardiovascular compromise including bronchospasm, chest pain, and hypotension [1]. HR to chemotherapy often prompt permanent discontinuation and may deprive the patient of the most active regimen.
Several authors have outlined re-treatment methods including desensitization with variable success [1], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. On the basis of our initial experience with platinum and taxane desensitization [18], [19], we employed a standard protocol that is effective for a significant number of patients, applicable to various chemotherapy and related agents, and adaptive for use in both inpatient and outpatient settings. The protocol was safe and uniformly successful for 57 patients who received a total of 255 planned courses. We present here the summary of our experience.
Section snippets
Methods
This study was a collaborative effort between the Medical Oncology service at the Dana-Farber Cancer Institute (DFCI) and the Allergy/Immunology service at the Brigham and Women's Hospital, and the study was approved by the Human Research Committee. Patients with documented HR to chemotherapy and related agents who required continued treatment with these agents, as recommended by their treating oncologists, were evaluated for desensitization. The inclusion criteria were: (1) age ≥18; (2)
Results
From February 2000 to February 2005, 57 consecutive patients who had moderate to severe HR to chemotherapy and related agents were evaluated for desensitization. Clinical characteristics of this population are outlined in Table 2.
All initial HR occurred during the infusion, and no patients reported delayed-onset symptoms. Patients who reacted to carboplatin received a median of 8 courses (range 5–15) before developing their initial HR compared with 17 of 22 patients with HR to paclitaxel who
Discussion
This paper outlines the rapid desensitization protocol used at our institution over a 5-year period. 57 patients with moderate to severe HR to chemotherapy and related agents successfully completed all 255 planned courses of desensitization. To our knowledge, this is the largest reported series of patients who underwent desensitization and is the first to use one standard protocol for various agents. In addition, this study is also the first to report systematic outpatient chemotherapy
Acknowledgments
The authors want to thank all the personnel at the DFCI for their invaluable collaboration and the patients presented in the study for their courage and determination. This study was supported in part by the Brigham and Women's Hospital Department of Medicine Innovation Program Support for the Rapid Desensitization Program for Adverse Drug Reactions.
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Note: An abstract containing parts of this work was presented at the 2005 ASCO Annual Meeting in Orlando.