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Kummar S Shafi NQ 《Clinical oncology (Royal College of Radiologists (Great Britain))》2003,15(5):288-294
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with the highest incidence in regions with high prevalence of chronic viral hepatitis infection, especially hepatitis B infection. HCC commonly metastasises to lungs, lymph nodes, adrenal gland and bones, including the skull. The overall prognosis of patients with metastatic HCC is poor. Randomised clinical trials are needed, which evaluate new treatment strategies and stratify patients on the basis of recent staging criteria and known prognostic indicators. This review presents a case report that illustrates the distinctive pathological features of metastatic HCC, along with a brief review of pathological features, staging, treatment and prognosis. 相似文献
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The treatment of patients with metastatic colon cancer has evolved tremendously over the past 10 years, with improved overall survival (OS) rates as a result of the advent of several important agents. Following the results of important adjuvant trials, the incorporation of oxaliplatin into the adjuvant setting has significantly increased the disease-free survival and OS rates in patients who undergo curative resection. However, still a significant number of patients will present with recurrent disease after being treated with oxaliplatin-containing chemotherapy regimens. Herein, we present approaches to the chemotherapeutic management of such patients with a review of the literature. 相似文献
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Larotrectinib efficacy and safety in adult patients with tropomyosin receptor kinase fusion sarcomas
Shivaani Kummar MD FACP Lin Shen MD David S. Hong MD Ray McDermott MD PhD Vicki L. Keedy MD Michela Casanova MD George D. Demetri MD Afshin Dowlati MD Soledad Gallego Melcón MD PhD Ulrik N. Lassen MD PhD Serge Leyvraz MD Tianshu Liu MD Victor Moreno MD PhD Jyoti Patel MD FASCO Tejas Patil MD Atrayee Basu Mallick MD Nuno Sousa MD Makoto Tahara MD PhD David S. Ziegler MBBS BSc FRACP MD Ricarda Norenberg MS Pierre Arvis MD Nicoletta Brega MD Alexander Drilon MD Daniel S. W. Tan MBBS PhD 《Cancer》2023,129(23):3772-3782
Background
Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas.Methods
Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100 mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021.Results
At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41–74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs.Conclusions
Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas.Plain Language Summary
- Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types.
- Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer.
- This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins.
- Over half of patients had a durable response to larotrectinib, with no unexpected side effects.
- These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas.
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Kummar S Kinders R Rubinstein L Parchment RE Murgo AJ Collins J Pickeral O Low J Steinberg SM Gutierrez M Yang S Helman L Wiltrout R Tomaszewski JE Doroshow JH 《Nature reviews. Cancer》2007,7(2):131-139
The optimal evaluation of molecularly targeted anticancer agents requires the integration of pharmacodynamic assays into early clinical investigations. Phase '0' trials conducted under the new Exploratory Investigational New Drug Guidance from the US Food and Drug Administration can provide a platform to establish the feasibility of assays for target modulation in human samples, evaluate biomarkers for drug effects and provide pharmacokinetic data. Phase 0 trials could facilitate rational drug selection, identify therapeutic failures early, and might compress timelines for anticancer drug development. We expect that such trials will become a routine part of early-phase oncological drug development in the future. 相似文献