Phase II Study of Plitidepsin 3-Hour Infusion Every 2 Weeks in Patients With Unresectable Advanced Medullary Thyroid Carcinoma

Baudin, Éric; Droz, J. P.; Paz‐Ares, Luis; Oosterom, A.T. van; Cullell-Young, Martín; Schlumberger, Martin

doi:10.1097/coc.0b013e31819fdf5e

Cited by 27 publications

(12 citation statements)

References 28 publications

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“…Results from other malignancies comprised: two PRs and one SD among 19 patients with unresectable advanced renal cell carcinoma, with a 2.1-month progression-free interval (PFI) (APL-B-001-01);41 11 SDs out of 16 patients with unresectable advanced medullary thyroid carcinoma, with a clinical benefit noted in only one patient (APL-B-002-02);42 three SDs in 17 patients with locally advanced or metastatic non-small-cell lung cancer, with a TTP of 1.2 months (APL-B-004-02);43 no responses in another trial of 19 patients with small-cell lung cancer pretreated with one line (APL-B-006-02);44 one SD as second-line therapy for 18 patients with advanced or metastatic transitional cell carcinoma of the urothelium (APL-B-005-02),45 two SDs among 22 assessable patients with advanced dedifferentiated liposarcomas, with a median PFS of 1.6 months (APIPLO study) 46. Coadministration of L-carnitine did not increase treatment efficacy and did not prevent the muscular toxicity or CPK-elevation associated with plitidepsin in patients with unresectable advanced renal cell carcinoma 41…”

Section: Developmentmentioning

confidence: 99%

Plitidepsin: design, development, and potential place in therapy

Alonso‐Álvarez

Pardal

Sánchez-Nieto

et al. 2017

DDDT

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Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin®. Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents. Single-agent plitidepsin has shown limited antitumor activity and a tolerable safety profile in several malignancies, such as noncutaneous peripheral T-cell lymphoma, melanoma, and multiple myeloma. In patients with relapsed or refractory multiple myeloma, plitidepsin activity seems to be enhanced after addition of dexamethasone while remaining well tolerated, and a Phase III trial comparing plitidepsin plus dexamethasone vs dexamethasone alone is underway. Additional studies are required to better define the role of plitidepsin in combination with other active agents in these indications. Results of plitidepsin activity in other hematological malignancies or solid tumors have been disappointing so far. Further studies analyzing its mechanisms of action and potential biomarkers will help select patients who may benefit most from this drug. In this review, we critically analyze the published studies on plitidepsin in hematological malignancies and solid tumors and discuss its current role and future perspectives in treating these malignancies. We also review its design, pharmaceutical data, and mechanism of action.

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Section: Developmentmentioning

confidence: 99%

Plitidepsin: design, development, and potential place in therapy

Alonso‐Álvarez

Pardal

Sánchez-Nieto

et al. 2017

DDDT

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“…Although QoL is reported in NET studies, the lack of standardisation of measurement tools between studies and the non-NET-specific nature of the tools used made comparing and generalising findings difficult. Table 4 provides a summary of the tools used to assess QoL in patients with NET (Aaronson et al 1993;O'Toole et al 2000;Larsson et al 2001Larsson et al , 2003Larsson et al , 2007Davies et al 2003Davies et al , 2006Major et al 2003;Pasieka et al 2004;Teunissen et al 2004;Frojd et al 2007Frojd et al , 2009Haugland et al 2009;Korse et al 2009;Muros et al 2009;Pezzilli et al 2009;Vinik et al 2009Vinik et al , 2011Baudin et al 2010;Beaumont et al 2010Beaumont et al , 2012. Our review showed that a variety of tools was used in patients with NET to assess disease-or treatmentrelated HRQoL and to evaluate global QoL, functioning, symptoms and mental well-being domains.…”

Section: Quality Of Lifementioning

confidence: 95%

Quality of life, resource utilisation and health economics assessment in advanced neuroendocrine tumours: a systematic review

Chau

Casciano²,

Willet³

et al. 2013

Eur J Cancer Care (Engl)

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Neuroendocrine tumours (NET) are often diagnosed at an advanced stage when the prognosis is poor for patients, who often experience diminished quality of life (QoL). As new treatments for NET become available, it is important to characterise the associated outcomes, costs and QoL. A comprehensive search was performed to systematically review available data in advanced NET regarding cost of illness/resource utilisation, economic studies/health technology assessment and QoL. Four rounds of sequential review narrowed the search results to 22 relevant studies. Most focused on surgical procedures and diagnostic tools and contained limited information on the costs and consequences of medical therapies. Multiple tools are used to assess health-related QoL in NET, but few analyses have been conducted to assess the comparative impact of available treatment alternatives on QoL. Limitations include English language and the focus on advanced NET; ongoing terminology and classification changes prevented pooled statistical analyses. This systematic review suggests a lack of comparative economic and outcomes data associated with NET treatments. Further research on disease costs, resource utilisation and QoL for patients with advanced NET is warranted.

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“…Later, similarly, weekly single‐agent plitidepsin at a dose of 3.2 mg/m 2 as second‐lined therapy showed no antitumor activity in treating patients with relapsed small‐cell lung cancer (PFS: 1.3 months; median OS: 4.8 months) . The same activity was seen in metastatic transitional cell carcinoma of the bladder with 1.4 months and 2.3 months in terms of PFS and OS, respectively , in unresectable advanced medullary thyroid carcinoma , and recently in liposarcoma (median PFS: 1.6 months; OS: 9.2 months) . As yet, a minor clinical response was seen with biweekly plitidepsin at a dose of 5 mg/m 2 in advanced melanoma (median PFS: 1.3 months; median OS: 3.5 months) .…”

Section: Targeting the Tumor Vasculature By Natural Compounds: Perspementioning

confidence: 98%

Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers

2018

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The high mortality associated with oncological diseases is mostly due to tumors in advanced stages, and their management is a major challenge in modern oncology. Angiogenesis is a defined hallmark of cancer and predisposes to metastatic invasion and dissemination and is therefore an important druggable target for cancer drug discovery. Recently, because of drug resistance and poor prognosis, new anticancer drugs from natural sources targeting tumor vessels have attracted more attention and have been used in several randomized and controlled clinical trials as therapeutic options. Here, we outline and discuss potential natural compounds as salvage treatment for advanced cancers from recent and ongoing clinical trials and real‐world studies. We also discuss predictive biomarkers for patients' selection to optimize the use of these potential anticancer drugs.

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Phase II Study of Plitidepsin 3-Hour Infusion Every 2 Weeks in Patients With Unresectable Advanced Medullary Thyroid Carcinoma

Abstract: Single-agent plitidepsin given as 3-hour i.v. infusions every 2 weeks was generally well tolerated but showed limited clinical activity in patients with unresectable advanced MTC.

Cited by 27 publications

References 28 publications

Plitidepsin: design, development, and potential place in therapy

Plitidepsin: design, development, and potential place in therapy

Quality of life, resource utilisation and health economics assessment in advanced neuroendocrine tumours: a systematic review

Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers

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