Abstract
BackgroundAdvanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited.MethodsThis 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.ResultsEighteen 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%.ConclusionsTrabectedin, 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
Highlights
Patients and methodsOvarian cancer (OC) is a major cause of cancer-related death among women [1], accounting for over 150,000 deaths worldwide in 2012
The standard of care when platinum-free interval (PFI) is ≥ 6 months is platinum-based chemotherapy, but evidence of survival benefit has been found with other combinations such as trabectedin + pegylated liposomal doxorubicin (PLD) [2, 3]
The progression of the trial is depicted in Supplementary Fig. S1
Summary
Patients and methodsOvarian cancer (OC) is a major cause of cancer-related death among women [1], accounting for over 150,000 deaths worldwide in 2012. Initial treatment is often effective, approximately 70% of women will experience relapse within 3 years [2]. In women who relapse within 6 months, there is evidence to support (non-platinum) monotherapy, but response rates are poor. The standard of care when PFI is ≥ 6 months is platinum-based chemotherapy, but evidence of survival benefit has been found with other combinations such as trabectedin + pegylated liposomal doxorubicin (PLD) [2, 3]. 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. Conclusions Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer.
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