Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas.
Angela BuonadonnaSimona ScaloneDavide LombardiArianna FumagalliAlessandra GuglielmiChiara LestuzziJerry PoleselVincenzo CanzonieriStefano LamonPetros GiovanisSara GagnoGiuseppe CoronaMaurizio MascarinClaudio BellucoAntonino De PaoliGianpiero FasolaFabio PuglisiGianmaria MioloPublished in: Cancers (2023)
Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m 2 ) on day 1 along with ifosfamide (3000 mg/m 2 on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29-0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73-0.90), while only 16% (95% CI: 0.08-0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity.
Keyphrases
- end stage renal disease
- drug delivery
- small cell lung cancer
- squamous cell carcinoma
- ejection fraction
- newly diagnosed
- chronic kidney disease
- soft tissue
- peritoneal dialysis
- cancer therapy
- multiple sclerosis
- prognostic factors
- cross sectional
- patient reported outcomes
- randomized controlled trial
- double blind
- drug release
- climate change
- human health
- recombinant human