Immediate hypersensitivity reaction to pegylated liposomal doxorubicin: management and outcome in four patients

Abstract Background Immediate hypersensitivity reaction to ursodiol is rare and there is no previously published protocol on ursodiol desensitization. Case presentation A 59-year-old woman with primary biliary cholangitis (PBC) developed an immediate hypersensitivity reaction to ursodiol—the first-line treatment for PBC. When she switched to a second-line treatment, her PBC continued to progress. As such, she completed a novel 12-step desensitization protocol to oral ursodiol. She experienced recurrent pruritus after each dose following desensitization, which subsided after a month of being on daily ursodiol. Conclusion Immediate hypersensitivity reaction to ursodiol is uncommon. Our case demonstrated that this novel desensitization protocol to ursodiol could be safely implemented when alternative options are not available or have proven inferior in efficacy.

Download Full-text

A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer

International Journal of Clinical Oncology ◽

10.1007/s10147-021-01973-1 ◽

2021 ◽

Author(s):

Shunji Takahashi ◽

Munetaka Takekuma ◽

Kenji Tamura ◽

Kazuhiro Takehara ◽

Hiroyuki Nomura ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase I ◽

Liposomal Doxorubicin ◽

Advanced Ovarian Cancer ◽

Pegylated Liposomal Doxorubicin ◽

Japanese Patients ◽

Pharmacokinetic Analysis ◽

Dependent Manner ◽

Drug Concentrations ◽

Grade 3

Abstract Background Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. Methods This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1. Results Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 reductions in neutrophil count, but these events were generally manageable through dose reduction and/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose-dependent manner. The overall response rate was 27.8%. Conclusions Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1 mg/m2 once every 21 days. Clinical trial registration number: JapicCTI-163164

Download Full-text