A Phase 1,Randomized, Double--blind, Placebo-controlled Study Assessing the Safety and Tolerability, the Pharmacodynamics and Pharmacokinetics of Single-ascending and Repeated Doses of Inhaled TPI 1100 in Healthy Subjects

This study will look at the safety and tolerability of TPI 1100 in healthy volunteers and look at pharmacodynamic (PD) effect on mRNA expression of PDE 4B/D & 7A in blood and in sputum.

开始日期2009-04-01

申办/合作机构

Syntara Ltd.

100 项与 TPI-1100 相关的临床结果

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100 项与 TPI-1100 相关的转化医学

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100 项与 TPI-1100 相关的专利（医药）

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项与 TPI-1100 相关的文献（医药）

2024-04-01·Advances in Therapy

Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis

Review

作者: Shergill, Suki ; Vetromilla, Bruna M ; Brennan, Victoria K ; Amoury, Nathalie ; Zanotto, Bruna S ; Agirrezabal, Ion ; Ziegelmann, Patricia K ; Azeredo-da-Silva, André L F ; Carion, Phuong L ; de Jesus, Victor Hugo F

INTRODUCTIONThis literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC).METHODSIn light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques.RESULTSFifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI.CONCLUSIONCurrent evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

2024-03-03·Expert Opinion on Pharmacotherapy

Fruquintinib as new treatment option in metastatic colorectal cancer patients: is there an optimal sequence?

Review

作者: Puccini, Alberto ; Daprà, Valentina ; Fazio, Roberta ; Bartolini, Michela ; Airoldi, Marco ; Prete, Maria Giuseppina ; Mondello, Giuseppe ; Stucchi, Erika ; Santoro, Armando

INTRODUCTIONAvailable treatments for colorectal cancer are limited. However, in the last few years several advances and new treatment options became available and expanded the continuum of care in metastatic colorectal cancer (mCRC).AREAS COVEREDFruquintinib, a tyrosine kinase inhibitor, has been shown to be effective in heavily pretreated mCRC progressing to trifluridine-tipiracil (FTD/TPI) or regorafenib or both. Preclinical studies have shown that fruquintinib inhibits with high selectivity VEGFR 1-2-3, leading to a blockade in angiogenesis process, but also acts, with weak inhibition, on RET, FGFR-1, and c-kit kinases. Fruquintinib demonstrated good efficacy and tolerance in chemorefractory mCRC in two phase III trial: FRESCO and FRESCO 2. These results led to FDA approval of fruquintinib for pretreated mCRC patients who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.EXPERT OPINIONFruquintinib is a valid therapeutic option for heavily pretreated mCRC patients. However, an optimal sequence of treatments is yet to be defined. In this review, we propose an algorithm for later lines of treatment to integrate fruquintinib as a standard of care together with the new therapeutic combinations that recently showed clinical benefit for chemorefractory mCRC, in both molecularly selected (e.g. KRAS^G12C or HER2 amplification) and in non-oncogenic driven patients.

2024-03-01·JCO Global Oncology

Efficacy of Chemotherapy Rechallenge Versus Regorafenib or Trifluridine/Tipiracil in Third-Line Setting of Metastatic Colorectal Cancer: A Multicenter Retrospective Comparative Study

Article

作者: Elhassan, Tusneem ; Bazarbashi, Shouki ; Aseafan, Mohamed ; Elsamany, Sherif ; Tuleimat, Yasmin ; Abdel-Aziz, Nashwa ; Alghamdi, Mohammed ; Mahrous, Mervat ; Alkhatib, Radwan

PURPOSE Metastatic colorectal cancer (mCRC) is a significant global health burden. This retrospective study compared the effectiveness of trifluridine/tipiracil (FTD/TPI), regorafenib, and chemotherapy rechallenge for third-line mCRC treatment. MATERIALS AND METHODS We reviewed the medical records of 132 patients with mCRC treated with regorafenib, FTD/TPI, or a rechallenge with the initial chemotherapy regimen in a third-line setting from four different institutions. The primary end point was progression-free survival (PFS). Secondary end points were objective response rate and overall survival (OS) across the three treatment approaches. RESULTS Twenty-nine patients received chemotherapy rechallenge, and 103 received FTD/TPI or regorafenib. Patients' characteristics were comparable, except for a lower number of left-sided primaries and KRAS wild-type tumors in the FTD/TPI-regorafenib group. The median PFS for the entire group was 3.0 months, and the median OS was 13.7 months. Chemotherapy rechallenge has resulted in a median PFS of 3.1 months and a median OS of 21.2 months, compared with 2.9 months (PFS) and 12.6 months (OS) for the FTD/TPI-regorafenib group. Multivariate analyses identified male sex and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 as independent prognostic factors for better PFS, whereas chemotherapy rechallenge, localized stage at diagnosis, and an ECOG PS of 0-1 were significant prognostic factors for better OS. CONCLUSION This study suggests that chemotherapy rechallenge may provide a survival benefit in the third-line treatment of mCRC. However, patient characteristics, such as sex and ECOG PS, should also be considered in treatment decisions. Further prospective studies are required to confirm our findings.

100 项与 TPI-1100 相关的药物交易

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