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Chapter-13 Principles of Chemotherapy

BOOK TITLE: Surgical Oncology: Fundamentals, Evidence-based Approaches and New Technology

Author
1. Carneiro Benedito A
2. Bahary Nathan
ISBN
9789350250518
DOI
10.5005/jp/books/11193_12
Edition
1/e
Publishing Year
2011
Pages
18
Author Affiliations
1. University of Pittsburgh, USA
2. University of Pittsburgh, USA
Chapter keywords

Abstract

The last 60 years since the discovery of the first chemotherapy drugs witnessed a major evolution on treatment of cancer and drug development strategies that have translated into improved prognosis of numerous malignancies. The shift in anticancer drug discovery from serendipitous identification of antiproliferative compounds to development of drugs specific to molecular defects contributing to carcinogenesis, resulted in targeted agents already incorporated into clinical practice and hundreds of new compounds are undergoing clinical testing. The enormous enthusiasm brought by these new drugs has been tempered by the relative lack of efficacy when these drugs are used alone showing the need to inhibit several pathways simultaneously in the complex molecular network that drives tumor growth. Adverse effects not seen previously with cytotoxic agents also represent a new challenge with these drugs. Nevertheless, significant advances in disease control and survival have been achieved through the addition of molecularly targeted agents to standard chemotherapy regimens in several malignancies. For instance, the median survival of patients with metastatic colorectal cancer more than doubled over the past decade (21-24 mo vs 10-12 mo) as a result of a number of factors including the efficacy of new cytotoxics (e.g. irinotecan and oxaliplatin), innovative administration of 5-FU and the addition of bevacizumab and cetuximab. The availability of more effective supportive drugs such as anti-emetics and bone marrow growth factors over the past two decades has also contributed to improve patients’ quality of life and the delivery of chemotherapy drugs. Furthermore, the foundations of personalized therapies in oncology built through the identification of molecular biomarkers able to identify the patients likely to benefit from novel therapies has evolved significantly in the last decade with numerous examples of molecular predictors used in clinical practice (e.g. KRAS mutational analysis to predict effectiveness of EGFR-based therapies in colorectal cancer; EGFR tyrosine kinase mutations that predict both resistance and sensitivity to EGFR therapies in lung cancer; gene signatures that indicate the likelihood of benefit from chemotherapy in early stage breast cancer). The combination of rapidly growing knowledge of the molecular underpinnings of carcinogenesis with the emergence of novel drugs will continue to contribute to the reduction of global cancer burden.

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