Clinical outcomes in extracranial tumor sites and unusual toxicities with concurrent whole brain radiation (WBRT) and Erlotinib treatment in patients with non-small cell lung cancer (NSCLC) with brain metastasis

Olmez, Inan; Donahue, Bernadine R.; Butler, James S.; Huang, Yiwu; Rubin, Philip; Xu, Yiqing

doi:10.1016/j.lungcan.2010.01.018

Cited by 40 publications

(32 citation statements)

References 22 publications

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“…Of the 12 original articles and 3 conference proceedings that matched the selection criteria and were included in this review, 6 evaluated erlotinib concurrent with WBRT (one study combined WBRT with SRS) [31][32][33][34][35][36], 4 evaluated gefitinib concurrent with WBRT [37][38][39][40] and in 3 studies both drugs were studied [41][42][43]. In 2 studies icotinib concurrent with WBRT was studied [44,45].…”

Section: Description and Quality Of The Studiesmentioning

confidence: 99%

“…For afatinib, crizotinib, ceritinib and alectinib no studies were found concurrent with cranial radiotherapy. Five studies were retrospective [33,[40][41][42][43]. 2 studies were phase I [32,45], 7 were phase II [31,[35][36][37][38][39]44], and there was only one phase III trial [34].…”

Section: Description and Quality Of The Studiesmentioning

confidence: 99%

“…EGFR-TKI were initiated from one week before the onset of cranial radiation to the first day of radiotherapy. In most studies, after WBRT, investigators could continue the EGFR-TKI at their own discretion [31][32][33][34][35][37][38][39][40][41][42][43][44][45]. Only in one study the EGFR-TKI was discontinued one month after completion of WBRT [36].…”

Section: Description and Quality Of The Studiesmentioning

confidence: 99%

“…9 trials (3 retrospective) specifically mentioned neurotoxicity [32][33][34][35]37,40,41,45] of which 5 reported that there was no increased neurotoxicity of the concurrent treatment [32,35,40,41,45]. However, in one of these studies 2 questionable late neurotoxicity events were reported: one 74-year old male developed dementia two years after study completion and one 56-year old female had 5 months after study completion intracranial progression for which she received SRS, she developed brain necrosis thereafter.…”

Section: Toxicity Outcomesmentioning

confidence: 99%

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Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non-small cell lung cancer patients: A systematic review

Hendriks¹,

Schoenmaekers²,

Zindler³

et al. 2015

Cancer Treatment Reviews

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Recently, non-small cell lung cancer (NSCLC) has been partly subclassified into molecularly-defined oncogene "addicted" tumors for which targeted agents are available. Tyrosine kinase inhibitors (TKI) are currently approved for patients with an activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. In these patients, brain metastases are often the first site of progression while on TKI treatment. The TKI may however still be active on extra-cranial sites and clinicians are thus faced with the question if the TKI may be continued during cranial radiotherapy. Advantages of combining TKI with cranial radiotherapy would be a possible synergistic effect on the brain metastases and the prevention of a systemic disease flare-up. A disadvantage is the possibly increased risk of (neuro)toxicity. The present systematic review addresses the toxicity of combining TKI with cranial radiotherapy in NSCLC patients.

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Section: Description and Quality Of The Studiesmentioning

confidence: 99%

Section: Description and Quality Of The Studiesmentioning

confidence: 99%

Section: Description and Quality Of The Studiesmentioning

confidence: 99%

Section: Toxicity Outcomesmentioning

confidence: 99%

See 2 more Smart Citations

Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non-small cell lung cancer patients: A systematic review

Hendriks¹,

Schoenmaekers²,

Zindler³

et al. 2015

Cancer Treatment Reviews

View full text Add to dashboard Cite

show abstract

“…(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) Whole-brain radiotherapy and stereotactic radiosurgery are the standard-of-care treatment options for patients with brain metastases from solid tumors. However, the long-term use of these modalities is limited by short-and long-term toxic effects to the brain with repeated use and increasing doses of radiation therapy.…”

Section: Introductionmentioning

confidence: 99%

Phase I clinical trial outcomes in 93 patients with brain metastases: The M. D. Anderson Cancer Center experience.

Iskander¹,

Tsimberidou²,

Letourneau³

et al. 2011

JCO

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Purpose-Patients with brain metastases are often excluded from clinical trials, but it is unclear if they pose an enhanced risk.Experimental Design-We reviewed the records of 1,181 consecutive patients, with and without brain metastases, treated in our Phase I Clinical Trials Program.Results-Ninety-three patients had brain metastases at the time of referral. Their median age was 54 years; median follow-up, 8 months. The rates of stable disease ≥ 4 months, partial, and complete response combined in patients with and without brain metastases were 17% and 27%, respectively (p= 0.03). Although the median survival of patients with brain metastases was shorter than that of patients without brain metastases (7.5 vs. 10.3 months; p = 0.002), in multivariate analysis the presence of brain metastases was not an independent factor predicting survival. There was no difference in time-to-treatment failure (1.74 vs. 1.84 months, respectively; p = 0.61) or in Grade 3-4 toxicity rates (including neurologic) (12% vs. 10%, respectively; p = 0.77) between patients with and without brain metastases.Conclusions-The rates of survival and response of patients with brain metastases were lower than those for other patients in the phase I setting, but the presence of brain metastases was not an independent prognostic factor predicting survival, indicating that other covariates that co-exist with brain metastases were more significant. Time-to-treatment failure for patients with brain metastases was not decreased, nor was the incidence of serious adverse effects (including neurologic toxicity) increased, suggesting that these patients should be eligible for early clinical trials.

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The theoretical foundation and research progress for WBRT combined with erlotinib for the treatment of multiple brain metastases in patients with lung adenocarcinoma

Zhuang

Wang

Zhao

et al. 2013

Intl Journal of Cancer

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Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung adenocarcinoma, and a theoretical basis exists for utilising whole brain radiotherapy (WBRT) combined with erlotinib for the treatment for brain metastases in patients with lung adenocarcinoma. This therapeutic regimen has the potential to be a revolutionary treatment for which the most appropriate indication is lung adenocarcinoma. Currently, there is no difference in the treatment of brain metastasis, especially multiple brain metastases, in patients with lung adenocarcinoma of patients with other lung carcinomas. Furthermore, limited clinical trials that combine a TKI with WBRT to treat multiple lung adenocarcinoma metastases have been conducted, and many clinical questions remain unanswered. Lung adenocarcinoma has a high propensity to metastasize to the brain, and targeted therapy has been widely used; however, clinical trials are necessary to provide data to support the combination of erlotinib and WBRT.

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Clinical outcomes in extracranial tumor sites and unusual toxicities with concurrent whole brain radiation (WBRT) and Erlotinib treatment in patients with non-small cell lung cancer (NSCLC) with brain metastasis

Cited by 40 publications

References 22 publications

Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non-small cell lung cancer patients: A systematic review

Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non-small cell lung cancer patients: A systematic review

Phase I clinical trial outcomes in 93 patients with brain metastases: The M. D. Anderson Cancer Center experience.

The theoretical foundation and research progress for WBRT combined with erlotinib for the treatment of multiple brain metastases in patients with lung adenocarcinoma

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