Introduction

During the past decade, research and clinical study across a wide front have made new progress against cancer, a disease once viewed as incurable and inexorable. Growing knowledge of the genetics, cytopathology, and biology of various types of cancer, along with a greater understanding of its causes and more sensitive and specific methods for detecting it, have been accompanied by remarkable advances in cancer treatment.

The American

Journal of Managed Care

In this supplement to , B. Jay Brooks, Jr, MD, chief of the department of hematology and oncology of the Ochsner Clinic Foundation, discusses several of the most important recent developments in the treatment of cancer, including newer chemotherapeutic agents and recently introduced monoclonal antibodies and other small-molecule treatment agents targeted at solid tumors and hematologic malignancies, against the background of clinical findings with these new agents in treating some of the most prevalent, problematic, and costly types of cancer.

Among the developments discussed in this supplement are studies of the treatment of non-small-cell lung cancer (NSCLC), the most prevalent form of lung cancer, with the recently introduced monoclonal antibodies gefitinib and erlotinib, both of which are directed at the epidermal growth factor receptor (EGFR) of epithelial cells. Seeking to explain why these 2 antibodies produce clinical responses in a subpopulation of patients with NSCLC, these studies strongly suggest that the therapeutic activity of these 2 antibodies depends on specific mutations in the gene that encodes EGFR, highlighting the potentially immense promise of genetic testing in optimizing clinical outcomes by matching patient-, tumor-, and treatment-agent-specific factors.

Further promise in the treatment of NSCLC has come from studies of its response to bevacizumab, a monoclonal antibody established in treating colorectal carcinoma, and which interferes with tumor development by blocking the effect of vascular endothelial growth factor, a peptide that promotes tumor vascularization. An ongoing study at Vanderbilt University has reported favorable interim results with bevacizumab combined with the cytotoxic chemotherapeutic agents paclitaxel and carboplatin in NSCLC.

A key factor in progress against cancer is its detection at an early stage, permitting its clinical extirpation before it has advanced beyond the point of curability. Among the most sensitive of recent techniques for detecting cancer through population-based screening is spiral computed tomography (CT). With spiral CT and the use of computer- assisted detection techniques, the International Early Lung Cancer Project, having screened more than 26 000 persons, has so far identified 82% of lung cancers while still in stage I, with a reported survival of greater than 95%, while efforts are actively under way at developing even more sensitive screening methods.¹

Ranking third among the most frequent types of cancer, behind disease of the prostate, breast, lungs, and bronchi, is colorectal carcinoma (CRC). Approximately two thirds of cases of CRC are in stage III or IV before being detected, and while the cure rate with surgical resection for stage III CRC ranges from 50% to 60%, efforts at improving this through adjuvant chemotherapy have continued since the first use of 5-fluorouracil (5-FU) for this purpose more than 4 decades ago.² Two large, recent studies, the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) and the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial, have found substantially longer disease-free survival in stage II or III CRC with use of the platinum-containing drug oxaliplatin in conjunction with the regimen of 5-FU and leucovorin, with further investigation of this regimen now under way.

In treating unresectable, advanced, and metastatic CRC, the monoclonal antibody bevacizumab has provided significant gains in the duration of response to treatment and in overall survival when used together with combination chemotherapeutic regimens of 5-FU, leucovorin, and either irinotecan or oxaliplatin, and cetuximab, a monoclonal antibody targeted at EGFR, may hold similar promise.

The past decade has seen revolutionary progress in the treatment of breast cancer, with the introduction of the hormone analogue tamoxifen and aromatase-inhibiting drugs for estrogen-and progesterone-receptor-bearing breast carcinomas and the monoclonal antibody trastuzumab for tumors expressing the human epidermal growth factor receptor 2 (HER2 receptor). Recent studies have found that the combination of trastuzumab with chemotherapy can provide important gains in response rates, durations of response, and survival in metastatic breast cancer, with manageable toxicity and dramatic improvements in disease-free survival when added to existing regimens of adjuvant therapy for resectable disease.

As in the various solid tumors discussed in this supplement, monoclonal antibodies are showing substantial promise in treating several types of non-Hodgkin's lymphoma, a group of hematologic malignancies that have remained clinically challenging despite nearly 4 decades of chemotherapy. In one such disease, diffuse large B-cell lymphoma, the monoclonal antibody rituximab, directed at the CD20 antigen present on the surfaces of B lymphocytes, has extended median survival to as long as 3.8 years when combined with the chemotherapeutic regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone developed nearly 4 decades ago at the Children's Hospital of Philadelphia as compared with a median of 1.1 years with the latter regimen alone. Retreatment of relapsed disease with rituximab has provided promise of further benefit, although the data for this are still limited and very preliminary. In other studies, rituximab has produced remarkable gains in response rate and overall survival when added to the regimen of cyclophosphamide, vincristine, and prednisone that has been a mainstay first-line treatment regimen for advanced follicular lymphoma, and is being actively examined for maintaining remissions of this disease.

As the 21st century unfolds, the developments discussed here are poised to become part of a major forward thrust in the understanding, diagnosis, and treatment of cancer.

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