Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy—A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

Postmus, P.E.; Haaxma-Reiche, Hanny; Smit, Egbert F.; Groen, Henk; Karnicka, H.; Lewiński, T; Meerbeeck, Jan P. van; Clerico, Mario; Gregor, A.; Curran, Desmond; Sahmoud, Tarek; Kirkpatrick, A.; Giaccone, Giuseppe

doi:10.1200/jco.2000.18.19.3400

Cited by 208 publications

(85 citation statements)

References 30 publications

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“…There were 1471 citations yielded, of which 1440 were removed during abstract review stage as being duplications or irrelevant to the specific question. The remaining 31 studies were to full text screening, and 19 RCTs were included (He et al, 2003;Guerrieri et al, 2004;Ge et al, 2005;Gao et al, 2009;Neuhaus et al, 2009;Dong et al, 2010;Gao, 2011;Pan et al, 2004;Peng et al, 2008;Postmus et al, 2000;Sun et al, 2009;Verger et al, 2005;Xiao et al, 2001;Xie et al, 2007;Zeng et al, 2009;Zhao et al, 2007;Zhu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The specifics of the chemotherapy regimens were listed in Zhao et al, 2007;Peng et al, 2008;Gao et al, 2009;Zeng et al, 2009;Zhu et al, 2009;Dong et al, 2010;Gao, 2011), one study according to RECIST (Sun et al, 2009), and 3 studies with unspecified the evaluation criteria (Postmus et al, 2000;He et al, 2003;Neuhaus et al, 2009). The assessments of the 19 studies by two independent reviewers were consistent.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…Figure 2 showed the results of authors' judgement of risk of biases. According to the bias risk assessment tool in the Cochrane systematic reviews handbook (Higgins et al, 2011), 6 RCTs (Postmus et al, 2000;Guerrieri et al, 2004;Verger et al, 2005;Zhao et al, 2007;Gao et al, 2009;Neuhaus et al, 2009) were randomized correctly using the method of random sequence Generation, one study (Xiao et al, 2001) was randomized incorrectly by grouping the patients in the order of admission, and the remain 12 RCTs were just mentioned "randomized" but unclear how to performed. Five RCTs used correct allocation concealment strategies (He et al, 2003;Ge et al, 2005;Sun et al, 2009;Xie et al, 2007;, but the other 14 failed to describe the methods of allocation concealment.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…Several studies demonstrated that WBRT plus chemotherapy is more effective than WBRT alone (Postmus et al, 2000;Xiao et al, 2001;He et al, …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Whole Brain Radiotherapy Plus Chemotherapy in the Treatment of Brain Metastases from Lung Cancer: A Meta-analysis of 19 Randomized Controlled Trails

Liu¹,

Zeng²,

Qin³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…Several studies demonstrated that WBRT plus chemotherapy is more effective than WBRT alone (Postmus et al, 2000;Xiao et al, 2001;He et al, …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Whole Brain Radiotherapy Plus Chemotherapy in the Treatment of Brain Metastases from Lung Cancer: A Meta-analysis of 19 Randomized Controlled Trails

Liu¹,

Zeng²,

Qin³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…testicular cancer, lymphoma, choriocarcinoma) are well known to respond to chemotherapy. A recent study by Postmus et al (2000) in patients with small-cell carcinoma and BM showed a 22% response rate to chemotherapy alone. However, the combination of chemotherapy and radiotherapy produced a 57% response rate and the control in the brain disease in these patients was longer than in patients who received only chemotherapy.…”

mentioning

confidence: 94%

Gemcitabine twice weekly as a radiosensitiser for the treatment of brain metastases in patients with carcinoma: a phase I study

et al. 2005

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Conventional treatment for brain metastases (BM) is whole-brain radiotherapy (WBRT). Efficacy is poor. It might be increased by a potent radiosensitiser such as gemcitabine which is believed to cross the disrupted blood -brain barrier. Primary objective of this study was to determine the maximum tolerated dose (MTD) of twice weekly gemcitabine given concurrently with WBRT. Patients with BM from carcinoma were included. The dose of WBRT was 30 Gys (10 daily fractions). Gemcitabine was given 2 -4 h prior to WBRT on days 1 and 8 for the first cohort of patients and then on days 1, 4, 8 and 11. Starting dose was 25 mg m À2 , escalated by 12.5 mg m À2 increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4 haematological or grade X3 nonhaematological toxicity. A total of 25 patients were included; 74% had a PS 1 (ECOG). In all, 23 had non-small-cell lung cancer, six colorectal, four breast, two renal cell and one oesophageal carcinoma. A total of 92% had concurrent extracranial disease. Six had single BM, 13 had two or three BM and six multiple. Up to 50 mg m À2 (level 4) no DLT was observed. At 62.5 mg m À2 , one out of six patients developed DLT (thrombocytopenia-bleeding). The next dose level (75 mg m À2 ) was abandoned after grade 4 bone marrow toxicity (fatal neutropenic sepsis) was seen in one out of two patients. So that the dose of 50 mg m À2 will be taken forward for further study. British Journal of Cancer (2005) (Patchel, 2003). Except for very few cases where surgery may be indicated, the mainstream accepted therapeutic modality is whole brain radiotherapy (WBRT). Gamma-knife radiosurgery and conformal radiotherapy are recent developments that may confer a prognosis improvement to selected patients mostly in cases of single BM and controlled extracranial disease. The prognosis of the vast majority of patients who develop BM is poor. The median survival for treated patients with WBRT is approximately 4 months and the 1-year survival only 12% (Lagerwaard et al, 1999). Chemotherapy is not usually given and if the patient is actually receiving chemotherapy, it is often discontinued. This attitude has been fostered by the theoretical difficulty of drugs to pass the blood -brain barrier and achieve therapeutic significance in brain micrometastases. This however is probably not the case with macroscopic metastases. Brain metastases in patients with many chemosensitive tumours (e.g. testicular cancer, lymphoma, choriocarcinoma) are well known to respond to chemotherapy. A recent study by Postmus et al (2000) in patients with small-cell carcinoma and BM showed a 22% response rate to chemotherapy alone. However, the combination of chemotherapy and radiotherapy produced a 57% response rate and the control in the brain disease in these patients was longer than in patients who received only chemotherapy. A phase III study of early vs late WBRT with concurrent cisplatin and vinorelbine in patients with non-smallcell lung cancer (NSCLC) and BM was reported by Robi...

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Whole brain radiotherapy for the treatment of multiple brain metastases

Tsao

Lloyd

Wong

et al. 2006

Cochrane Database of Systematic Reviews

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None of the RCTs with altered dose-fractionation schemes as compared to standard delivery (3000 cGy in ten fractions) found a benefit in terms of overall survival, neurologic function, or symptom control. The use of radiosensitizers or chemotherapy in conjunction with WBRT remains experimental. A radiosurgery boost with WBRT may improve local disease control in selected patients, although survival remains unchanged. The benefit of WBRT as compared to supportive care alone has not been studied in RCTs. It may be that supportive care alone, without WBRT, may be appropriate for some patients, particularly those with advanced disease and poor performance status.

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Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy—A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

Abstract: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.

Cited by 208 publications

References 30 publications

Whole Brain Radiotherapy Plus Chemotherapy in the Treatment of Brain Metastases from Lung Cancer: A Meta-analysis of 19 Randomized Controlled Trails

Whole Brain Radiotherapy Plus Chemotherapy in the Treatment of Brain Metastases from Lung Cancer: A Meta-analysis of 19 Randomized Controlled Trails

Gemcitabine twice weekly as a radiosensitiser for the treatment of brain metastases in patients with carcinoma: a phase I study

Whole brain radiotherapy for the treatment of multiple brain metastases

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