Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: Standard protocol effective in 57 patients for 255 courses

Abstract

Objectives.

Hypersensitivity reactions (HR) to chemotherapy often prompt permanent discontinuation and deprive the patient of the most active regimen. We investigated the safety and effectiveness of a rapid desensitization protocol used in inpatient and outpatient settings for patients with HR to various chemotherapy and related agents.

Methods.

A 3-solution, 12-step protocol delivered doubling drug doses by step, infusing the target dose over 5.8 h for inpatient and 3.8 h for outpatient administration.

Results.

57 consecutive patients who had moderate to severe HR to chemotherapy were evaluated for desensitization. All 57 patients successfully completed 255 courses of desensitization (127 to carboplatin, 114 to paclitaxel, and 14 to four other agents) where 16 patients received 51 courses in the outpatient setting (34 to carboplatin and 17 to paclitaxel). 225 courses (88.2%) were completed without any HR. 18 patients had breakthrough symptoms (BS) over 30 courses (11.8%) that were less severe than their initial HR. After management of breakthrough symptoms, these patients finished all 30 courses and tolerated subsequent desensitizations on a modified protocol. 21 of 26 patients (81%) with HR to carboplatin had positive skin tests to carboplatin. Cancer response to chemotherapy administered by desensitization was within the expected range after 1–3 years of follow-up.

Conclusion.

The rapid desensitization protocol was safe and effective in both the inpatient and outpatient settings and allowed appropriate patients with moderate to severe HR to continue chemotherapy. This study warrants the incorporation of the protocol into standard clinical practice.

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.