Case Report
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The retreatment of carboplatin via high-dose intraperitoneal chemotherapy in patients with a history of a hypersensitivity reaction Mark A. Rettenmaier, MD; Crystal M. Gray, PA-C; Katrina L. Lopez; Karen A. Bechtol, RN; Bram H. Goldstein, PhD
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ild to moderate hypersensitivity reactions (HSR) attributed to platinum-based chemotherapy are an anticipated occurrence.1,2 Following HSR, the physician has to either forego the affecting agent or consider the medication for another line of therapy in conjunction with chemotherapy desensitization.3 Hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial because of the reportedly severe myelosuppression.3,4 Nevertheless, because HIPEC is administered under general anesthesia and the chemotherapy essentially remains localized,5 a patient with a previous HSR could be retreated with the same compound using this procedure. We present 3 ovarian cancer patients with a history of HSR who, in the absence of chemotherapy desensitization, were successfully retreated via HIPEC in accordance with an institutional review boardeapproved protocol; written consent was obtained from each patient prior to study participation.
C ASE R EPORTS Case 1 A 58-year-old woman with advancedstage ovarian cancer underwent optimal From Gynecologic Oncology Associates (Drs Rettenmaier and Goldstein, Ms Gray, and Ms Bechtol) and Women’s Cancer Research Foundation (Ms Lopez), Newport Beach, CA. Received Sept. 5, 2013; revised Oct. 17, 2013; accepted Oct. 29, 2013. Supported by the Nancy Yeary Women’s Cancer Research Foundation. The authors report no conflict of interest. Reprints: Bram H. Goldstein, PhD, Gynecologic Oncology Associates, 351 Hospital Rd., Suite 507, Newport Beach, CA 92663.
[email protected]. 0002-9378/free ª 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.10.883
A hypersensitivity reaction attributed to platinum-based chemotherapy is a relatively common occurrence. Hyperthermic intraperitoneal chemotherapy potentially facilitates the safe retreatment of platinum therapy following this complication. We describe 3 ovarian cancer patients who were successfully retreated with carboplatin via hyperthermic intraperitoneal chemotherapy following hypersensitivity reaction. Key words: carboplatin, gynecologic oncology, hypersensitivity reactions, hyperthermic intraperitoneal chemotherapy debulking surgery in August 2005. She subsequently completed 6 cycles of paclitaxel (175 mg/m2) and carboplatin (5 area under the curve [AUC]), from which she obtained a complete response. In February 2007, the patient exhibited progressive disease and reinitiated paclitaxel and carboplatin chemotherapy. During cycle 7, the patient experienced a grade-2 HSR, characterized by bronchospasms and palmar erythema; hydrocortisone sodium succinate (100 mg) was provided and her symptoms resolved. In January 2013, the patient developed recurrent disease and was slated for 1 cycle of HIPEC. Initially, similar to the patient’s previous intravenous therapy, premedications comprising palonosetron (0.25 mg) and dexamethasone (8 mg) were administered. A 4-cm midline skin incision was made and carried through the abdominal layers; a GelPort (Applied Medical Resources, Rancho Santa Margarita, CA) system was then placed in the abdominal incisions. The 2 inflow and outflow tubes for the HIPEC ThermoChem HT-1000R device (ThermaSolutions Inc, St Paul, MN) were positioned intraabdominally. Carboplatin (8 AUC) was mixed in 2500 mL of normal saline and then added to the inflow fluid. Thereafter, continuous circulation of the infusate was maintained with a change in temperature of 1.01.5 C for 90 minutes until a uniform intraperitoneal temperature of 41.5 C was attained.
When the procedure concluded, the chemotherapy-containing infusate was completely removed and the abdominal cavity was flushed with 2 L of lactated Ringer’s solution. The patient had an uncomplicated intraoperative and postoperative course. The patient was neither rechallenged with carboplatin nor did she undergo a chemotherapy desensitization protocol.
Case 2 A 59-year-old woman with advancedstage ovarian carcinoma underwent optimal tumor debulking surgery in February 2013. She was treated with 6 cycles of weekly paclitaxel (80 mg/m2) and monthly carboplatin (6 AUC) to which she obtained a complete response; following cycle 6, the patient developed a grade-2 HSR, which resulted in angina pectoris, tachycardia, asthenia, palmar erythema, and allergic rhinitis. She received hydrocortisone sodium succinate (100 mg), and her symptoms promptly resolved. Despite the HSR, she was considered for 1 cycle of consolidation HIPEC with the intent to sustain her remission; as in case 1, the patient was initially treated with palonosetron and dexamethasone premedication. Subsequently, carboplatin (8 AUC) was administered in accordance with physician discretion. Following treatment, she had an uncomplicated intraoperative/postoperative course and has since remained disease
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Case Report free. Moreover, there was no intention to ultimately rechallenge the patient with carboplatin or employ chemotherapy desensitization.
Case 3 A 62-year-old woman with advancedstage ovarian carcinoma underwent optimal debulking surgery in April 2010. The patient received 6 cycles of weekly adjuvant paclitaxel (80 mg/m2) and monthly carboplatin (6 AUC) chemotherapy, to which she achieved a complete clinical response. In March 2012, the patient exhibited recrudescent disease and began paclitaxel (175 mg/m2) and carboplatin (6 AUC) chemotherapy; however, upon starting cycle 5, the patient developed a grade-2 HSR, characterized by palmar erythema; following intravenous diphenhydramine (50 mg), the patient’s condition dramatically improved. In July 2013, the disease recurred again and the patient underwent debulking surgery, of which only miliary disease remained. Following palonosetron and dexamethasone therapy, 1 cycle of HIPEC with carboplatin (10 AUC) was administered; the patient experienced an uncomplicated intraoperative/ postoperative course. Henceforth, the patient was neither scheduled for platinum retreatment nor chemotherapy desensitization.
www.AJOG.org C OMMENT We described 3 ovarian cancer patients with a history of HSR who were successfully retreated with carboplatin via HIPEC. Because HIPEC is administered under general anesthesia, the patient’s vital signs are closely monitored within a precisely controlled environment and thus, the risk of HSR occurring is significantly attenuated. However, we recognize that anaphylaxis and bronchospasms cannot be necessarily circumvented during general anesthesia.6 As none of the patients were physically compromised by a recent debulking surgery, one could also surmise that having an intact peritoneum prevented systemic chemotherapy extravasation.7 Additionally, during HIPEC, the chemotherapy is abstracted following a short dwell time and thus, this method of administration is ostensibly a viable alternative. When treating these patients, we never intended to employ HIPEC as a desensitization option or to rechallenge them with intravenous carboplatin, particularly because of the inherent risk for developing a more severe HSR.8 We nevertheless recognize that HIPEC remains highly controversial because of the attendant patient toxicity. Therefore, in the absence of a well-designed HIPEC dose escalation study, the
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