Phase I trial of pemetrexed in combination with cetuximab and concurrent radiotherapy in patients with head and neck cancer

Argiris, Athanassios; Karamouzis, M. V.; Smith, Ryan P.; Kotsakis, A.; Gibson, Michael K.; Lai, Stephen Y.; Kim, S.; Branstetter, Barton F.; Shuai, Yongli; Romkes, Marjorie; Wang, L.; Grandis, Jennifer R.; Ferris, Robert L.; Johnson, Jonas T.; Heron, Dwight E.

doi:10.1093/annonc/mdr002

Cited by 12 publications

(11 citation statements)

References 32 publications

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“…Conversely the MTHFR-A1298A genotype was associated with significantly shorter OS in patients with recurrent or metastatic head and neck cancer treated within a phase II trial of pemetrexed and bevacizumab [27]. However, both MTHFR-A1298C and the MTHFR-C677T SNP did not correlate with response rate, survival or severity of treatment-related toxic effects in patients with head and neck cancer treated with pemetrexed in combination with cetuximab and concurrent radiotherapy [28].…”

Section: Discussionmentioning

confidence: 83%

Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed–carboplatin

et al. 2012

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Section: Discussionmentioning

confidence: 83%

Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed–carboplatin

et al. 2012

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“…This suggested that there are several plausible mechanisms to explain the increased rate of infectious complications in advanced cancer patients treated with cetuximab. EGF and EGF-like protein families, such as heparin-binding EGF-like growth factor (HB-EGF), are essential for cell proliferation, differentiation, and wound healing [25], [26]. Cetuximab may target the bone marrow EGF receptors, which are expressed on he surface of neutrophils and play key roles in their proliferation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

Infectious Complications in Head and Neck Cancer Patients Treated with Cetuximab: Propensity Score and Instrumental Variable Analysis

Lee

Hsiao

et al. 2012

PLoS ONE

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BackgroundTo compare the infection rates between cetuximab-treated patients with head and neck cancers (HNC) and untreated patients.MethodologyA national cohort of 1083 HNC patients identified in 2010 from the Taiwan National Health Insurance Research Database was established. After patients were followed for one year, propensity score analysis and instrumental variable analysis were performed to assess the association between cetuximab therapy and the infection rates.ResultsHNC patients receiving cetuximab (n = 158) were older, had lower SES, and resided more frequently in rural areas as compared to those without cetuximab therapy. 125 patients, 32 (20.3%) in the group using cetuximab and 93 (10.1%) in the group not using it presented infections. The propensity score analysis revealed a 2.3-fold (adjusted odds ratio [OR] = 2.27; 95% CI, 1.46–3.54; P = 0.001) increased risk for infection in HNC patients treated with cetuximab. However, using IVA, the average treatment effect of cetuximab was not statistically associated with increased risk of infection (OR, 0.87; 95% CI, 0.61–1.14).ConclusionsCetuximab therapy was not statistically associated with infection rate in HNC patients. However, older HNC patients using cetuximab may incur up to 33% infection rate during one year. Particular attention should be given to older HNC patients treated with cetuximab.

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“…The majority of these patients were treated with cetuximab plus cisplatin/paclitaxel/radiotherapy (UPCI 05-003, ref. 17) or cetuximab plus pemetrexed/radiotherapy (UPCI 05-005, ref. 18).…”

Section: Methodsmentioning

confidence: 99%

Cetuximab-Activated Natural Killer and Dendritic Cells Collaborate to Trigger Tumor Antigen–Specific T-cell Immunity in Head and Neck Cancer Patients

Srivastava

Lee

Filho

et al. 2013

Clinical Cancer Research

281

278

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Purpose Tumor antigen (TA)-specific monoclonal antibodies (mAb) block oncogenic signaling and induce Fcγ receptor (FcγR)-mediated cytotoxicity. However, the role of CD8+ cytotoxic T lymphocyte (CTL) and FcγR in initiating innate and adaptive immune responses in mAb-treated human cancer patients is still emerging. Experimental Design FcγRIIIa codon 158 polymorphism was correlated with survival in 107 cetuximab-treated head and neck cancer (HNC) patients. Flow cytometry was performed to quantify EGFR-specific T cells in cetuximab-treated HNC patients. The effect of cetuximab on NK cell, dendritic cell (DC), and T cell activation was measured using IFN-γ release assays and flow cytometry. Results FcγR IIIa polymorphism did not predict clinical outcome in cetuximab-treated HNC patients, however elevated circulating EGFR -specific CD8+ 853-861 T cells were found in cetuximab-treated HNC patients (p<0.005). Cetuximab promoted EGFR-specific cellular immunity through the interaction of EGFR+ tumor cells and FcγRIIIa on NK cells, but not on the polymorphism per se. Cetuximab-activated NK cells induced IFN-γ dependent expression of DC maturation markers, antigen presentation machinery (APM) components such as TAP-1/2, and Th1 chemokines through NKG2D/MICA binding. Cetuximab initiated adaptive immune responses via NK-cell induced DC maturation, which enhanced cross-presentation to CTL specific for EGFR as well as another TA, MAGE-3. Conclusion Cetuximab-activated NK cells promote DC maturation and CD8+ T cell priming, leading to TA spreading and Th1 cytokine release through ‘NK-DC cross-talk.’ FcγRIIIa polymorphism did not predict clinical response to cetuximab, but was necessary for NK-DC interaction and mAb induced cross-presentation. EGFR-specific T cells in cetuximab treated HNC patients may contribute to clinical response.

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Phase I trial of pemetrexed in combination with cetuximab and concurrent radiotherapy in patients with head and neck cancer

Abstract: The addition of pemetrexed 500 mg/m(2) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients.

Cited by 12 publications

References 32 publications

Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed–carboplatin

Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed–carboplatin

Infectious Complications in Head and Neck Cancer Patients Treated with Cetuximab: Propensity Score and Instrumental Variable Analysis

Cetuximab-Activated Natural Killer and Dendritic Cells Collaborate to Trigger Tumor Antigen–Specific T-cell Immunity in Head and Neck Cancer Patients

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