Suppressive effect upon carboplatin hypersensitivity reaction via pegylated liposomal doxorubicin combination therapy
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ORIGINAL ARTICLE
Suppressive effect upon carboplatin hypersensitivity reaction via pegylated liposomal doxorubicin combination therapy Kyoko Shimada1 · Shoji Nagao1 · Kazuhiro Suzuki1 · Takashi Shibutani1 · Kasumi Yamamoto1 · Tomoatsu Jimi1 · Hiroko Yano1 · Miho Kitai1 · Takaya Shiozaki1 · Satoshi Yamaguchi1 Received: 25 March 2020 / Accepted: 7 May 2020 © Japan Society of Clinical Oncology 2020
Abstract Background Occurrence of hypersensitivity reaction (HSR) in patients having received multiple doses of carboplatin has been reported. Several studies demonstrated reduction of carboplatin-associated HSR with in combination with pegylated liposomal doxorubicin (PLD). The objective of this study was to determine the suppressive effect on carboplatin-induced HSR via combined treatment with PLD within clinical practice. Methods We reviewed the medical records of women with primary or recurrent ovarian, fallopian tube, or peritoneal cancer treated with carboplatin containing regimen at our hospital between January 2009 and March 2019. We compared the incidence of carboplatin-induced HSR among patients who received more than one cycle of PLD plus carboplatin (PLD-C) therapy (i.e., PLD-C group) versus patients who never received PLD-C therapy (non-PLD-C group). Results A total of 414 women were included in this study (48: PLD-C group, 366: non-PLD-C group). Carboplatin-induced HSR occurred in 34 total patients (8.2%) [1/48 (2.1%) in the PLD-C group and 33/366 (9.0%) in the non-PLD-C group], with a median cycle number of carboplatin administration at onset of HSR being 9. Incidences of carboplatin-induced HSR within the PLD-C versus non-PLD-C group at the 8th, 12th, and 16th cycles of carboplatin administration were 2.2% vs 11.2%, 2.2% vs 28.6%, and 2.2% vs 39.1%, respectively [hazard ratio: 19.2 (95% confidence interval: 9.82–39.4), p 7 treatment cycles [6]. Up to half of patients who experienced carboplatin-induced HSR, even though a significant proportion experienced only mild-to-moderate symptoms, had their platinum-based therapy regimen prematurely discontinued, despite the use of platinum re-challenge protocols [7]. Therefore, carboplatin-induced HSR could present significant challenge for treatment of epithelial ovarian cancer, particularly in patients with platinum-sensitive recurrent cancer. Pegylated liposomal doxorubicin (PLD) is a liposomal formed doxorubicin characterized by extended circulation and increased tumor uptake as well as pharmacokinetics [8]. A phase III study conducted by a Gynecologic Cancer Intergroup (CALYPSO study) compared the efficacy and safety between PLD plus carboplatin (PLD-C) therapy and paclitaxel plus carboplatin (TC) therapy for treatment of platinum-sensitive recurrent ovarian cancer [9]. The study demonstrated improved prolonged progression-free survival
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(PFS) in the PLD-C group (median PFS: 11.3 months vs 9.4 months; hazard ratio: 0.82; p = 0.005), without improvement of overall survival (OS). Additionally, lower risks of toxicity were observed,
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