Feasibility and tolerability of the addition of erlotinib to 3D thoracic radiotherapy (RT) in patients (p) with unresectable NSCLC: A prospective randomized phase II study

Martı́nez, Enrique; Martinez, M.; Viñolas, Núria; Casas, Francesc; Torre, Antonio de la; Valcárcel, Francisco; Minguez, J.; Paredes, Alfredo; Casas, Adriana; Dómine, Manuel

doi:10.1200/jco.2008.26.15_suppl.7563

Cited by 21 publications

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“…The last study published by Radiation Therapy Oncology Group (RTOG) was a phase II study of chemoradiotherapy with carboplatin and paclitaxel plus cetuximab in patients with stage III NSCLC [60]. The combination of cetuximab with CRT is feasible and ing results without an increase in toxicity [52]. Adverse events related to radiotherapy included esophagitis, radiation dermatitis, and pneumonitis.…”

Section: Discussionmentioning

confidence: 99%

Combining Systemic Therapies with Radiation in Non-small Cell Lung Cancer

Adamowicz¹,

Goszczynska-Matysiak²

2015

Klin Onkol

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SummaryRadiotherapy has been the mainstay of treatment of stage III non-small cell lung cancer patients. In the early 90s, combined treatment with chemotherapy was introduced. In 1995, a meta-analysis showed improved treatment outcome of the sequential use of cisplatin-based chemotherapy and radiotherapy compared to radiotherapy alone. Subsequent randomized studies and two meta-analyses demonstrated that concurrent radiochemotherapy is superior (local control and overall survival) to sequential usage of both method. However, several questions remain unanswered concerning the optimal chemotherapy regimen and radiotherapy doses and techniques in terms of treatment outcome and toxicity profi le. Targeted therapies represent a new class of drugs, which interfere with specifi c molecular targets (typically proteins) playing critical roles in tumor growth and progression. Some combinations appear to be too toxic, such as the vascular epithelial growth factor antibody bevacizumab. The feasibility of adding the epidermal growth factor receptor inhibitor cetuximab has been recently reported for non-small cell lung cancer patients. Strategies to incorporate safely novel antiangiogenic agents into combined-modality therapy in lung cancer are needed. Hopefully, rapid development of molecular oncology will contribute to better patient selection to particular strategies and to treatment optimization. Increasing radiotherapy doses applied according to up-to-date techniques and combinations with new bio logicals might lead to further treatment improvements. Key words lung neoplasms -chemotherapy -radiotherapy -drug therapy SouhrnRadioterapie je hlavní léčebnou modalitou při léčbě III. stadia nemalobuněčného plicního karcinomu. Na počátku 90. let 20. století byla zavedena kombinovaná léčba s chemoterapií. V roce 1995 prokázala metaanalýza zlepšené výsledky léčby při sekvenčním použití chemoterapie a radioterapie založené na cisplatině v porovnání se samotnou radioterapií. Následné randomizované studie a dvě metaanalýzy prokázaly, že současně používaná radiochemoterapie převyšuje sekvenční používání obou metod v celkovém přežití i lokální kontrole onemocnění. Přesto zůstává v rámci výsledků léčby a profi lu toxicity nezodpovězeno několik otázek, včetně optimálního režimu chemoterapie a dávky a techniky radioterapie. Cílená léčba představuje novou třídu léčiv, která reagují se specifi ckými molekulárními cíli (typicky proteiny), které hrají klíčovou roli v růstu nádoru a progresi. Ně kte ré kombinace se jeví jako příliš toxické, jako třeba protilátka proti vaskulárnímu epiteliálnímu růstovému faktoru -bevacizumab. Možnost přidání inhibitoru receptoru epidermálního růstového inhibičního faktoru cetuximabu byla nedávno popsána u pa cientů s nemalobuněčným karcinomem plic. Jsou zapotřebí vyvinout strategie, jak bezpečně začlenit nová antiangiogenní agens do kombinované terapie u rakoviny plic. Rychlý rozvoj molekulární onkologie snad přispěje k lepšímu výběru pa cientů pro jednotlivé strategie a k optimalizaci léčby. K dalšímu zlepše...

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Section: Discussionmentioning

confidence: 99%

Combining Systemic Therapies with Radiation in Non-small Cell Lung Cancer

Adamowicz¹,

Goszczynska-Matysiak²

2015

Klin Onkol

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“…The response of 6 months of erlotinib maintenance therapy, following erlotinib combined with a synchronic pectoral radiotherapy of 66 Gy in 30 patients with LA-NSCLC, was evaluated in a recent clinical trial, and the effective rate in the erlotinib-treated group was found to be higher than the radiotherapy-treated group alone (83 vs. 56%) (10). At present, a clinical trial is under way with a focus on the evaluation of the response of erlotinib combined with synchronic pectoral radiotherapy in LA-NSCLC patients (RT0901).…”

Section: Discussionmentioning

confidence: 99%

Mutation and expression of multiple treatment response-related genes in a population with locally advanced non-small cell lung cancer

Pan

et al. 2011

Oncology Letters

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Abstract. Individual therapy based on various pathohistological types and biological characteristics may be the practical trend of advanced non-small cell lung cancer (NSCLC) treatment. To provide a molecular criterion for drug selection, we investigated the incidence of somatic mutation and mRNA expression levels of common genes relevant to treatment response in a population with locally advanced NSCLC. Mutant-enriched and branched DNA-liquidchip technology (bDNA-LCT) were used to detect the somatic mutations in the epidermal growth factor receptor (EGFR), KRAS, BRAF and phosphatidylinositol-3-kinase catalytic α (PIK3CA) genes, and mRNA levels of EGFR, ERCC1, class III β-tubulin (TUBB3) and TYMS, separately, in paraffin tissue blocks from 30 patients with stage IIIA NSCLC. Our current findings revealed that 6, 4 and 2 out of 30 samples were found with mutations in exons 19, 21 and 20 of the EGFR gene, respectively. The mutation incidence of exons 19 and 21 had a positive correlation with EGFR mRNA expression. Mutations in exons 12 and 13 of the K-ras gene were found in 2 out of 30, and 1 out of 30 samples, separately. Three out of 30 samples were found with mutations in codon 542 of the PIK3CA gene. No mutations were found in the BRAF gene. The expression levels of ERCC1 and TUBB3 mRNAs were higher in patients with adenocarcinoma than those in patients with squamous cell carcinoma. The expression of TYMS mRNA in patients with adenocarcinoma was lower than that in patients with squamous cell carcinoma. In conclusion, mutations and mRNA expression of these commonly studied genes provides a basis for the selection of suitable molecular markers for individual treatment in a population with locally advanced NSCLC.

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“…In a prospective randomized phase II study, erlotinib was administered in addition to 3D thoracic RT in patients with unresectable stage I-IIIA NSCLC and not suitable to receive chemotherapy [74]. Patients were enrolled to receive RT over 33 fractions during 6 weeks in arm A or RT at same modality with concomitant erlotinib at the dose of 150 mg once daily in arm B.…”

Section: Targeted Therapy and Radiotherapymentioning

confidence: 99%

Combination of radiotherapy and targeted therapies in the treatment of locally advanced non-small cell lung cancer

et al. 2011

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Lung cancer is the most common cancer in the world. One third of patients with non-small cell lung cancer (NSCLC) are diagnosed with locally or regionally advanced unresectable disease at presentation. Currently, in this stage of disease, a combination of chemotherapy and radiotherapy is the standard treatment approach for patients with good performance status, and concomitant chemo-radiotherapy has demonstrated to be the best therapeutic approach. However, despite improvements in treatment, local tumor control remains suboptimal and distant metastases remain the major site of failure. The diversity of molecular abnormalities in NSCLC may partly contribute to its resistance to therapy. It is therefore widely accepted that one approach to improve the efficacy of cancer therapy is the development of rational combinations of anticancer agents that may exhibit synergistic interactions. The introduction of several biologic agents represents an important advance in the management of NSCLC and some of them have shown to have a synergistic effect when given in combination with radiotherapy and chemotherapy in preclinical and in clinical models. In the present review we discuss the rationale and the feasibility of these combinations and the first results available from clinical trials.

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Feasibility and tolerability of the addition of erlotinib to 3D thoracic radiotherapy (RT) in patients (p) with unresectable NSCLC: A prospective randomized phase II study

Cited by 21 publications

References 0 publications

Combining Systemic Therapies with Radiation in Non-small Cell Lung Cancer

Combining Systemic Therapies with Radiation in Non-small Cell Lung Cancer

Mutation and expression of multiple treatment response-related genes in a population with locally advanced non-small cell lung cancer

Combination of radiotherapy and targeted therapies in the treatment of locally advanced non-small cell lung cancer

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