Neoadjuvant therapy:

EAdjunctive or adjuvant therapy given prior to the primary therapy. Example: Sometimes chemotherapy is given to shrink the tumor so that surgery can be effective on tumors that were inoperable before the chemotherapy.

Introduction

Neoadjuvant therapy, an adjunctive therapy given before a definitive treatment, is an essential component of modern multidisciplinary cancer therapy. Although neoadjuvant or induction therapy does not contribute the most to the treatment outcome, it may improve the result substantially. For example, neoadjuvant therapy allows patients with large breast cancer to undergo breast-conserving surgery. It enables patients with locally advanced laryngeal cancer to have their vocal function preserved. Many patients with rectal cancer can avoid permanent colostomy after undergoing this approach. In addition, in certain cancers, neoadjuvant therapy may improve long-term survival. Recent years have seen an increase in the popularity of this treatment technique. The number of clinical trials on this topic published from 2000 to 2003 exceeded the number published during the entire previous decade.

This review summarizes the outcomes of neoadjuvant therapy for common malignant solid tumors. Since many patients rely on non-oncologists for guidance and support during cancer treatment, understanding the rationale and benefit of neoadjuvant therapy may aid primary care physicians in providing support and encouragement to their patients, ultimately improving care and treatment outcomes. The effect of neoadjuvant therapy can be delineated by comparing it with main therapy alone, or in some cancers, with main therapy plus adjuvant therapy, an adjunctive therapy given after the main treatment modality. This review, organized by organ of primary cancer, puts emphasis on long-term survival and organ preservation based on large phase III randomized, controlled trials.

Neoadjuvant therapy has its downside. Many neoadjuvant therapy regimens are cumbersome, requiring a highly motivated patient. For instance, one neoadjuvant therapy regimen for rectal cancer calls for weekly 2-hour infusional chemotherapy for 6 weeks, followed by a pause of 2 weeks.[1] The regimen goes on with daily 5-day intravenous chemotherapy at the beginning of daily 5-week radiation therapy, and another 5-day chemotherapy during the last week of radiation. There is a mandatory pause of up to 8 weeks before surgery, the definitive therapy, to allow maximal tumor shrinkage. The duration of neoadjuvant therapy in this regimen adds up to about 6 months. Unlike an immediate removal of the tumor, prolonged neoadjuvant therapy for resectable cancer can be physically, socially, and emotionally difficult for patients, especially those with gynecologic malignancy.[2] In addition, ineffective neoadjuvant therapy simply means a delay of the definitive treatment and an increase in treatment-related toxicities.

Given these uncertain data, the historical justification for neoadjuvant therapy besides the proven decrease of mastectomies, while it cannot be dismissed, cannot be considered convincing. Happily, a new and sound rationale for the neoadjuvant approach is available.

Molecular biologists have now provided the clinical oncologist with an extraordinarily rich and powerful range of new tools with which to improve our understanding of breast cancer and enhance its treatment. The promise is that in the near future it will be possible to tailor therapy to the particular characteristics of an individual tumor, so bringing an end to the era in which a particular therapy was administered blindly to all comers.

The work of Colleoni et al. stands as an example of how the importance of biological determinants can be established [9, 10]. Prospectively derived data suggest that response to either AC chemotherapy or the 5-fluorouracil/leucovorin/vinorelbine combination is predicted by factors such as p53 and c-erbB-2 positivity and a high or decreasing Mib1/Ki67 percentage in the tumor sample. According to these data, relative resistance to the chemotherapy regimens cited is predicted by ER and progesterone receptor (PgR) positivity.The neoadjuvant approach has been criticized in some quarters since it is held to prevent use of lymph node status as a guide to prognosis. It is argued that eradication of tumor from lymph nodes that were positive before neoadjuvant therapy might lead certain patients to receive insufficiently intensive adjuvant treatment. However, surgeons experienced in the field may be able to use sentinel lymph node biopsy to determine whether nodes were initially positive. The issue is being investigated in the European Organization for Research and Treatment of Cancer-AMAROS study. This trial should enable biological data from the tumor sample to be correlated with primary clinical and lymph node response.

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