Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment

Becker, Annemarie; Crombag, Laurence; Heideman, Daniëlle A.M.; Thunnissen, Erik; Wijk, A.W. van; Postmus, Pieter E.; Smit, Egbert F.

doi:10.1016/j.ejca.2011.06.046

Cited by 98 publications

(87 citation statements)

References 14 publications

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“…Several strategies were applied in this situation: switching from gefitinib to erlotinib, retrial of the same EGFR-TKI after a drug 'holiday', and high-dose therapy of gefitinib or erlotinib [24][25][26][27]. It seems that gefitinib failed to show any benefit after disease progression compared to erlotinib treatment because the recommended daily dose of erlotinib is much nearer to the maximum tolerated dose (MTD) than that of gefitinib [28].…”

Section: Discussionmentioning

confidence: 99%

The Continuation of Erlotinib Treatment in Non-Small Cell Lung Cancer Patients Whose Brain Lesion Is the Only Site of Progression: Prospective Pilot Study

et al. 2015

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Section: Discussionmentioning

confidence: 99%

The Continuation of Erlotinib Treatment in Non-Small Cell Lung Cancer Patients Whose Brain Lesion Is the Only Site of Progression: Prospective Pilot Study

et al. 2015

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“…Rapid cancer progression ("disease flare") was reported in NSCLC patients who discontinued EGFR TKIs while awaiting further chemotherapy, indicating the necessity for possible minimization of washout periods for patients when switching to another treatment modality (Chaft et al, 2011). However, regain of sensitivity upon retreatment with erlotinib (after a "drug holiday") was demonstrated for NSCLC patients who switched to conventional chemotherapy but responded initially to erlotinib (Becker et al, 2011). Moreover, there are indications of improved clinical outcome for patients continuing TKIs after initiating chemotherapy (Goldberg et al, 2013, as TKI-sensitive clones may still remain after the acquisition of resistance to EGFR TKIs.…”

Section: Combinatory Treatment Of Lung Adenocarcinomamentioning

confidence: 99%

Cell death in cancer therapy of lung adenocarcinoma

Zagryazhskaya

Gyurászová²,

Zhivotovsky

2015

Int. J. Dev. Biol.

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Lung cancer is the main cause of all cancer-related deaths in the world, with lung adenocarcinoma (ADC) being the most common subtype of this fatal disease. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new cancer therapy approaches. The high resistance of lung ADC to conventional radio-and chemotherapies represents a major challenge to treatment effectiveness. Here we discuss recent progress in understanding the mechanisms of ADC's broad resistance to treatment and its possible therapeutic implications. A number of driving oncogenic alterations were identified in a subset of lung ADCs, making them suitable for targeted therapies directed towards specific cancer-associated molecular changes. In addition, we discuss the molecular aberrations common in lung ADC that are currently being exploited or are potentially important for targeted cancer therapy, as well as limitations of this type of therapy. Furthermore, we highlight possible treatment modalities that hold promise for overcoming resistance to targeted therapies as well as alternative treatment options such as immunotherapies that are potentially promising for improving the clinical outcome of lung ADC patients.

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“…However, progressive disease on a first-generation tki according to the formal Response Evaluation Criteria in Solid Tumors does not necessarily mean exhausted utility, because abrupt tki cessation can, in about 20% of patients, induce a significant "flare" phenomenon that responds to immediate re-introduction of the same tki 39 . Also, rechallenge with the same tki after a "holiday" (during which chemotherapy may be given) is increasingly recognized as valuable 40,41 . There is an unmet need for biomarkers to guide the management of patients who experience technical progressive disease in front-line tki, and there is evidence that resistance may differentially affect some metastases and not others-that is, clonal metastasis 42,a .…”

Section: Egfrmentioning

confidence: 99%

Biomarkers That Currently Affect Clinical Practice: EGFR, ALK, MET, KRAS

et al. 2012

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New drugs such as pemetrexed, the epidermal growth factor receptor (egfr) tyrosine kinase inhibitors, and the Alk inhibitor crizotinib have recently enabled progress in the management of advanced non-smallcell lung cancer (nsclc). More drugs, especially Met inhibitors, will follow. However, the benefits of these agents are not uniform across the spectrum of nsclc, and optimizing their utility requires some degree of subgrouping of nsclc by the presence or absence of certain biomarkers.The biomarkers of current or imminent value are EGFR and KRAS mutational status, ALK rearrangements, and MET immunohistochemistry. As a predictor of benefit for anti-egfr monoclonal antibodies, EGFR immunohistochemistry is also of potential interest.Some of the foregoing biomarkers (EGFR, ALK, MET) are direct drivers of the malignant phenotype. As such, they are, quite rationally, the direct targets of inhibitory drugs. However, KRAS, while definitely a driver, has resisted attempts at direct pharmacologic manipulation, and its main value might lie in its role as part of an efficient testing algorithm, because KRAS mutations appear to exclude EGFR and ALK mutations. The indirect value of KRAS in determining sensitivity to other targeted agents or to pemetrexed remains controversial. The other biomarkers (EGFR, ALK, MET) may also have indirect value as predictors of sensitivity to chemotherapy in general, to pemetrexed specifically, and to radiotherapy and molecularly targeted agents.These biomarkers have all enabled the co-development of new drugs with companion diagnostics, and they illustrate the paradigm that will govern progress in oncology in the immediate future. However, in nsclc, the acquisition of sufficient biopsy material remains a stubborn obstacle to the evolution of novel targeted therapies.

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Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment

Cited by 98 publications

References 14 publications

The Continuation of Erlotinib Treatment in Non-Small Cell Lung Cancer Patients Whose Brain Lesion Is the Only Site of Progression: Prospective Pilot Study

The Continuation of Erlotinib Treatment in Non-Small Cell Lung Cancer Patients Whose Brain Lesion Is the Only Site of Progression: Prospective Pilot Study

Cell death in cancer therapy of lung adenocarcinoma

Biomarkers That Currently Affect Clinical Practice: EGFR, ALK, MET, KRAS

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