Drug radiotherapy combinations: Review of previous failures and reasons for future optimism

•Combined chemo-radiotherapy typically improves clinical outcomes but increases side-effects.•Trials with targeted radiosensitising and hypoxia modifying drugs have been disappointing.•The reasons for this include a lack of biomarkers to identify those patients likely to benefit.•New drug strategies...

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Vydáno v:	Cancer treatment reviews Ročník 41; číslo 2; s. 105 - 113
Hlavní autoři:	Higgins, Geoff S., O’Cathail, Sean M., Muschel, Ruth J., McKenna, W. Gillies
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier Ltd 01.02.2015
Témata:	Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cell Hypoxia - drug effects Chemo-radiotherapy Chemoradiotherapy - adverse effects Chemoradiotherapy - methods Chemoradiotherapy, Adjuvant - adverse effects Clinical Trials as Topic Combined Modality Therapy - methods DNA Repair - drug effects Drug-radiotherapy combinations Hematology, Oncology and Palliative Medicine Humans Immunotherapy Molecular Targeted Therapy - methods Neoplasms - genetics Neoplasms - metabolism Neoplasms - physiopathology Neoplasms - therapy Radiation-Sensitizing Agents - administration & dosage Radiation-Sensitizing Agents - adverse effects Radiosensitisation Signal Transduction - drug effects Treatment Failure Tumour hypoxia Drug-radiotherapy combinations Chemo-radiotherapy Radiosensitisation Tumour hypoxia
ISSN:	0305-7372, 1532-1967, 1532-1967
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Popis
Shrnutí:	•Combined chemo-radiotherapy typically improves clinical outcomes but increases side-effects.•Trials with targeted radiosensitising and hypoxia modifying drugs have been disappointing.•The reasons for this include a lack of biomarkers to identify those patients likely to benefit.•New drug strategies to augment radiotherapy offer great cause for optimism. Combining chemotherapy with radiotherapy has resulted in significant clinical improvements in many different tumour types. However, the non-specific mechanisms by which these drugs exert their effects mean that this is often at the expense of increased side effects. Previous attempts at using targeted drugs to induce more tumour specific radiosensitisation have been generally disappointing. Although cetuximab, an EGFR monoclonal antibody, resulted in improved overall survival in HNSCC when combined with radiotherapy, it has failed to show benefit when added to chemo-radiotherapy. In addition, our inability to successfully use drug treatments to reverse tumour hypoxia is underlined by the fact that no such treatment is currently in widespread clinical use. The reasons for these failures include the lack of robust biomarkers, and the previous use of drugs with unacceptable side-effect profiles. Despite these disappointments, there is reason for optimism. Our improved understanding of key signal transduction pathways and of tumour specific DNA repair deficiencies has produced new opportunities to specifically radiosensitise tumours. Novel strategies to reduce tumour hypoxia include the use of drugs that cause vascular normalisation and drugs that reduce tumour oxygen consumption. These new strategies, combined with better compounds at our disposal, and an ability to learn from our previous mistakes, mean that there is great promise for future drug-radiotherapy combinations to result in significant clinical benefits.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	0305-7372 1532-1967 1532-1967
DOI:	10.1016/j.ctrv.2014.12.012