Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma

Neyns, Bart; Sadones, Jan; Joosens, E.; Bouttens, Frank; Verbeke, L.; Baurain, J.; D’Hondt, Lionel; Strauven, Theo; Chaskis, Cristo; Veld, Peter In’t; Michotte, Alex; Grève, Jacques De

doi:10.1093/annonc/mdp032

Cited by 221 publications

(145 citation statements)

References 49 publications

Supporting

Mentioning

137

Contrasting

Unclassified

Order By: Relevance

“…6,7 On the other hand, it was demonstrated that the anti-EGFR mAb cetuximab is effective both in vitro and in vivo using human GBM cell lines; 8 however, the use of cetuximab in GBM patients has been limited partly because of severe toxicities (grade 3 or 4 acne-like rash, hypersensitivity and serious adverse effect, 9 and its limited activity as single agent in patients with progressive high-grade gliomas in a stratified phase II trial. 10 In general, EGFR-targeted agents with a high toxicity profile may be not suitable as an add-on therapy to the standard of care in GBM.…”

Section: Introductionmentioning

confidence: 99%

Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in combination with temozolomide and radiation therapy for newly diagnosed glioblastoma multiforme: First results in Chinese patients

Wang

Pan

Sheng

et al. 2014

Asia-Pac J Clncl Oncology

View full text Add to dashboard Cite

Aim: To evaluate the safety and efficacy of nimotuzumab, a humanized monoclonal antibody specific for the epidermal growth factor receptor (EGFR), in combination with temozolomide (TMZ) and radiation therapy (RT) in the treatment of newly diagnosed glioblastoma (GBM) in Chinese patients. Methods: Twenty-six patients with newly diagnosed GBM were enrolled. All patients received standard external beam RT after surgery, with a total dose of 60 Gy in 30 fractions. During RT, concurrent TMZ was given daily at 75 mg/m 2 for 40-42 days, combined with six weekly infusions of nimotuzumab at a 200 mg dose. After a 4-week interval upon completion of RT, six cycles of adjuvant TMZ (150 to 200 mg/m 2 for 5 days in each 28-day cycle) were given. The primary end point was 6-month progression-free survival (PFS) rate. EGFR expression in tumor tissues was analyzed by immunohistochemistry. Results: Treatment was well tolerated and no grade III or higher grade toxicity was observed. Median PFS and overall survival (OS) were 10.0 and 15.9 months, respectively, while the 6-month PFS and OS rates were 69.2% and 88.5%, respectively. No correlation between efficacy and EGFR expression was found. Conclusions: Combination of Nimotuzumab with RT plus concomitant and adjuvant TMZ showed favorable safety and tolerability profiles in newly diagnosed GBM in Chinese patients. The survival times were similar to those seen in historical data of standard therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in combination with temozolomide and radiation therapy for newly diagnosed glioblastoma multiforme: First results in Chinese patients

Wang

Pan

Sheng

et al. 2014

Asia-Pac J Clncl Oncology

View full text Add to dashboard Cite

show abstract

“…In fact, several small-molecule EGFR-inhibitors such as gefitinib and erlotinib have been used in clinical trials but progression-free survival was not prolonged (van den Bent, et al, 2009). The inability to increase survival of GBM patients was also observed with lapatanib (EGFR/HER-2 inhibitor) (Neyns, et al, 2009;Thiessen, et al, 2009), and with the cetuximab, the monoclonal antibody against EGFR (Neyns, et al, 2009). The unsuccess of EGFR inhibitors in GBM treatment seems to be associated to the inactivation of PTEN and to the activation of the PI3K/Akt.…”

Section: Signaling Pathways Altered In Gbmmentioning

confidence: 99%

Genetics and Biology of Glioblastoma Multiforme

Carmo¹,

Crespo²,

Lopes³

2011

Molecular Targets of CNS Tumors

View full text Add to dashboard Cite

“…However, the maximum tolerated dose of gefitinib could be 500 to 1000 mg/kg depending on the concomitant use of non-EIAEDs or EIAEDs respectively [33]. Cetuximab, an EGFR antagonist showed limited toxicity and activity against recurrent GBM independently of the EGFR status of the tumors [34]. Overall, studies on EGFR inhibitors found no significant activity of these agents in high-grade gliomas [35].…”

Section: Molecular Targeted Therapiesmentioning

confidence: 99%

An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting

Kyritsis

Levin

2011

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

To cite this version:Athanassios P. Kyritsis, Victor A. Levin. An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting. Cancer Chemotherapy and Pharmacology, Springer Verlag, 2011, 67 (5) Results. In order to guide practice in the general oncology setting an algorithm was constructed according to the activity of the reported chemotherapies at the time of writing.There are some molecular studies, performed on tumor tissue that may help to guide selection of chemotherapy. Methylated MGMT in tumor tissue correlates with increased sensitivity to alkylating agents such as fotemustine or other nitrosoureas. Depending on MGMT status and bone marrow reserve, treatment with fotemustine, bevacizumab, bevacizumab with irinotecan, or cis-retinoic acid (cRA), might be of value.Conclusion. Unfortunately, progress in the development of new and more effective chemotherapy agents has been very limited and leaves the clinician treating high-grade glioma patients at relapse with few good options. The suggested algorithm is our objective evaluation of the currently existing knowledge. Hopefully, ongoing phase II and III trials will provide us the needed chemotherapy agents in the years to come.3

show abstract

Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma

Abstract: Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.

Cited by 221 publications

References 49 publications

Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in combination with temozolomide and radiation therapy for newly diagnosed glioblastoma multiforme: First results in Chinese patients

Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in combination with temozolomide and radiation therapy for newly diagnosed glioblastoma multiforme: First results in Chinese patients

Genetics and Biology of Glioblastoma Multiforme

An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting

Contact Info

Product

Resources

About