A Feasibility Study of Extended Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Phase II Trial of Cancer and Leukemia Group B

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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“…In several trials, improved 1-and 2-year overall survival rates in favor of the concurrent arm were reported [18][19][20][21][22][23].…”

Section: Radiochemotherapy In Locally Advanced Nsclcmentioning

confidence: 99%

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

Adamowicz¹,

Goszczynska-Matysiak²

2015

Klin Onkol

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“…In several trials improved 1- and 2-year overall survival rates in favour of the concurrent arm were reported [17–23]. …”

Section: Sequential Versus Concurrent Radiochemotherapymentioning

confidence: 99%

From Cisplatin-Containing Sequential Radiochemotherapy towards Concurrent Treatment for Patients with Inoperable Locoregional Non-Small Cell Lung Cancer: Still Unanswered Questions

Koning

Belderbos

Uitterhoeve

2010

Chemotherapy Research and Practice

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Radiotherapy has been the mainstay of the treatment of stage III non-small cell lung cancer (NSCLC) patients. In the early nineties, combined treatment with chemotherapy was introduced. In 1995, a meta-analysis showed improved treatment outcome of the sequential use of radiochemotherapy (RCT) compared to radiotherapy alone, provided cisplatin was part of the chemotherapy course. Concurrent RCT compared to radiotherapy only yielded the same improvements of 4% in the 2-year and 2% in the 5-year overall survival rates. Just recently, two meta-analyses demonstrated that concurrent RCT is definitely superior to sequential RCT in terms of local control and 2-, 3-, and 5-year survival. However, several unanswered questions remain concerning the optimal chemotherapy regimen and radiotherapy doses and techniques in terms of treatment outcome and toxicity profile. Arguments supporting a daily low-dose cisplatin scheme are presented because of comparable radiosensitizing characteristics and favourable side effects. Increasing radiotherapy doses applied according to up-to-date techniques and combinations with new biologicals might lead to further treatment improvements.

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“…Randomised clinical trials and metaanalyses have generally shown trends in favour of combination chemoradiotherapy compared with radiotherapy alone [14][15][16][17][18][19][20][21][22][23], as well as concomitant compared with sequential chemoradiotherapy [24][25][26][27][28][29][30]. However, many patients are considered unsuitable for chemoradiotherapy, particularly with concurrent administration, due to poor performance status or the presence of serious comorbidities.…”

Section: Introductionmentioning

confidence: 99%

Current status of and future strategies for multimodality treatment of unresectable stage III nonsmall cell lung cancer

Huber¹,

Reck

Thomas

2013

Eur Respir J

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Stage III nonsmall cell lung cancer (NSCLC) encompasses a heterogeneous group of patients, some of whom may be candidates for potentially curative surgery, although for the majority surgery is not an option. Recommended therapy for patients with unresectable stage III disease is concurrent treatment with chemotherapy and thoracic radiotherapy, although even with this dual modality therapy survival remains disappointing. Novel classes of agents including targeted therapies have been shown to improve survival in advanced stage NSCLC, raising the possibility that these agents may have benefits in multimodal therapy when combined with chemoradiotherapy. Here we consider the rationale for combining new agents with chemoradiotherapy and the evidence from clinical studies assessing multimodal strategies for the management of patients with unresectable stage III NSCLC. @ERSpublications The rationale for combining new agents with chemoradiotherapy to treat stage III NSCLC and data from clinical studies http://ow.ly/nuE1d

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A Feasibility Study of Extended Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Phase II Trial of Cancer and Leukemia Group B

Cited by 28 publications

References 15 publications

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

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

From Cisplatin-Containing Sequential Radiochemotherapy towards Concurrent Treatment for Patients with Inoperable Locoregional Non-Small Cell Lung Cancer: Still Unanswered Questions

Current status of and future strategies for multimodality treatment of unresectable stage III nonsmall cell lung cancer

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