Pharmacokinetics, safety, and activity of trabectedin as first-line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group
| Autor: | D. Comandini, Maurizio D'Incalci, Domenico Marra, Cristina Matteo, Giacomo Siri, Federica Grosso, Massimo Zucchetti, Marina Bergaglio, Andrea Decensi, Giovanni Grignani, Emanuela Marchesi, Emanuela Palmerini, Toni Ibrahim, Giacomo Giulio Baldi, Stefano Tamberi, Eliana Rulli, Lorenzo D'Ambrosio |
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| Přispěvatelé: | Grosso F., D'Ambrosio L., Zucchetti M., Ibrahim T., Tamberi S., Matteo C., Rulli E., Comandini D., Palmerini E., Baldi G.G., DeCensi A., Bergaglio M., Marra D., Marchesi E., Siri G., D'Incalci M., Grignani G. |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Anthracycline Cmax Phases of clinical research Antineoplastic Agents Neutropenia elderly unfit patients 03 medical and health sciences 0302 clinical medicine Interquartile range Internal medicine medicine 80 and over Humans 030212 general & internal medicine pharmacokinetic Antineoplastic Agents Alkylating Trabectedin Aged Aged 80 and over business.industry Soft tissue sarcoma Sarcoma advanced soft tissue sarcoma medicine.disease Alkylating pharmacokinetics trabectedin Female Italy Oncology 030220 oncology & carcinogenesis business medicine.drug |
| Zdroj: | CancerReferences. 126(21) |
| ISSN: | 1097-0142 |
| Popis: | Background Although elderly patients (≥70 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline-based chemotherapy. Trabectedin is registered as a second-line treatment for advanced STS and is characterized by a favorable safety profile. Methods The aim of this single-arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3-1.5 mg/m2 ) as a first-line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline-based chemotherapy. The coprimary endpoints were progression-free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics. Results Twenty-four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74-83 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3-6), with 7 patients (29%) receiving ≥6 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%-81%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%-57%]) experienced CLTs. Trabectedin Cmax , half-life, clearance, and distribution volume were 1.28 ng/mL (standard deviation [SD], 0.58 ng/mL), 26.70 hours (SD, 9.09 hours), 39.98 L/h/m2 (SD, 14.08 L/h/m2 ), and 1460 L/m2 (SD, 561 L/m2 ), respectively. Conclusion Trabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data. |
| Databáze: | OpenAIRE |
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