Successful Rechallenge to Etoposide After an Acute Vasomotor Response
Authors: William J. Tester, Jeffrey B. Cohn, Phillip D. Fleekop, Marc S. Rabinowitz, Jamie S. Lieberman
Journal: Journal of Clinical Oncology (1991)

To the Editor: Athanassiou et al describe their experience with acute vasomotor responses to etoposide (VP-16) in four of 31 consecutive patients given VP-16 for advanced ovarian cancer. Similar adverse reactions to epipodophyllotoxins have been reported by others and consist of the acute development of hypertension, tachycardia, flushing, substernal chest discomfort, and sweating. The symptoms abate with discontinuation of the VP-16 infusion, and none of these patients were rechallenged. One of our patients recently had a similar reaction to VP-16, and we now report our successful rechallenge and continued use of VP-16 with a change of rate of delivery and with premedication. A 57-year-old man with metastatic germ cell carcinoma was placed on a standard regimen of cisplatin, VP-16, and bleomycin. His first cycle was tolerated without any adverse reaction. Three weeks later, he was admitted for a second cycle of chemotherapy. His VP-16 was mixed at a concentration of 200 mg in 250 cc normal saline solution and was administered over 1 hour. Immediately after the infusion had begun, he experienced flushing, diaphoresis, substernal chest discomfort, and elevated blood pressure to 190/90 requiring discontinuation of the infusion. Urinary histamine was not elevated. Because VP-16 was felt to be a critical part of his chemotherapy regimen with potential for a cure, it was decided to rechallenge him to VP-16. The patient was moved to the intensive care unit where he was premedicated with corticosteroids, H1 and H2 blockers, and carefully rechallenged with VP-16 as follows: 0.2 mg/50 cc normal saline solution (NSS) over 30 minutes, 2 mg/50 cc NSS over 30 minutes, 20 mg/50 cc NSS over 30 minutes, and 200 mg/50 cc NSS over 4 hours. He tolerated this without any complications. On subsequent treatment days, he was premedicated with 6 mg intravenous diphenhydramine. VP-16 was administered in concentrations of 2 mg/50 cc NSS over 30 minutes followed by 200 mg/500 cc NSS over 4 hours. This 5-day course was completed without any adverse reactions. He was readmitted 3 and 6 weeks later and the same challenge protocol was used, allowing four complete cycles of chemotherapy to be given. In this case we were able to continue to use VP-16 after an acute vasomotor reaction with premedication and a lower infusion rate. The etiology of the acute vasomotor response to etoposide remains unclear. It is also unclear whether the use of premedication, the slow infusion rate, or both permitted our patient to tolerate continued administration of VP-16. The following is a correction of errors in the letter-to-the-editor entitled "Successful Rechallenge to Etoposide After an Acute Vasomotor Response" by Tester et al (J Clin Oncol 8:1600–1601, 1990). The last sentence of the third paragraph should have read: "The patient was moved to the intensive care unit where he was premedicated with corticosteroids, H1 and H2 blockers, and carefully rechallenged with VP-16 as follows: 0.2 mg/50 cc normal saline solution (NSS) over 30 minutes, 2 mg/50 cc NSS over 30 minutes, 20 mg/50 cc NSS over 30 minutes, and 200 mg/500 cc NSS over 4 hours." The second sentence of the fourth paragraph should have read: "On subsequent treatment days, he was premedicated with 6 mg intravenous dexamethasone and 25 mg intravenous diphenhydramine."