Response to chemotherapy, reexposure to crizotinib and treatment with a novel ALK inhibitor in a patient with acquired crizotinib resistance.

نویسندگان

  • Kathrin Schrödl
  • Christoph von Schilling
  • Amanda Tufman
  • Rudolf Maria Huber
  • Fernando Gamarra
چکیده

The treatment of advanced non-small cell lung cancer (NSCLC) has dramatically changed over the last decade. It has developed from an unspecific approach based on platinum doublet chemotherapy to a personalized, molecularly targeted therapy. Crizotinib is a new tyrosine kinase inhibitor approved for the treatment of NSCLC with gene rearrangement of EML4 and ALK. Despite good initial responses, patients treated with crizotinib relapse after an average of 10 months. In this case report, we present a patient with acquired crizotinib resistance whose adenocarcinoma responded to a second course of crizotinib following a drug holiday and chemotherapy with pemetrexed. This is the second case report to suggest that retreatment with crizotinib is an option for patients with initial benefit from ALK inhibition.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Patient harboring a novel PIK3CA point mutation after acquired resistance to crizotinib in an adenocarcinoma with ROS1 rearrangement: A case report and literature review

ROS1 rearrangement occurs in 1-2% of non-small cell lung cancer (NSCLC) cases. These patients would benefit from treatment with the anaplastic lymphoma kinase inhibitor, crizotinib; however, resistance to crizotinib inevitably develops in such patients despite an initial response. The mechanism of acquired resistance to crizotinib in patients with NSCLC with ROS1 rearrangement has not yet been ...

متن کامل

Cancer Therapy: Preclinical Co-Clinical Trials Demonstrate Superiority of Crizotinib to Chemotherapy in ALK-Rearranged Non–Small Cell Lung Cancer and Predict Strategies to Overcome Resistance

Purpose: To extend the results of a phase III trial in patients with non–small cell lung cancer with adenocarcinomas harboring EML4-ALK fusion. Experimental Design:We conducted a co-clinical trial in a mouse model comparing the ALK inhibitor crizotinib to the standard-of-care cytotoxic agents docetaxel or pemetrexed. Results: Concordant with the clinical outcome in humans, crizotinib produced a...

متن کامل

Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance.

PURPOSE To extend the results of a phase III trial in patients with non-small cell lung cancer with adenocarcinomas harboring EML4-ALK fusion. EXPERIMENTAL DESIGN We conducted a co-clinical trial in a mouse model comparing the ALK inhibitor crizotinib to the standard-of-care cytotoxic agents docetaxel or pemetrexed. RESULTS Concordant with the clinical outcome in humans, crizotinib produced...

متن کامل

Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib.

PURPOSE The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC). Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to...

متن کامل

Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

Around 4% of advanced non-small-cell lung cancers (NSCLCs) have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Respiration; international review of thoracic diseases

دوره 88 3  شماره 

صفحات  -

تاریخ انتشار 2014