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Since the first use of intravenous nitrogen mustard as a chemotherapeutic agent to treat cancer in the 1940s, a number of chemotherapy agents have been successfully developed over the past half century with improved efficacy and toxicity profile. The advent of targeted therapies has further increased the arsenal of available cancer therapies.
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Surgery and radiation play a primary role in control of localized tumors, and as adjuncts to chemotherapy in relieving symptoms in metastatic disease, and need to be considered in developing the overall treatment plan.
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With the multitude of cancer therapies and treatment modalities, the decision to choose the best therapeutic regimen for an individual can be complex. Conceptually, both host and tumor-related factors need to be carefully considered in the decision-making process and personalizing therapy (1). The general principles involved in deciding the optimal cancer pharmacotherapy for an individual are reviewed in this introductory chapter.
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1. Goal of therapy
In general, the goal of treatment of localized disease is different from metastatic disease. Therapy in metastatic disease is directed toward improvement in quality of life and prolongation of survival, while in localized disease the overarching goal is cure. For localized disease one is willing to take “higher toxicity” for the price of potential cure. However, for metastatic disease quality of life is an important consideration. Multiple studies in various solid tumors have shown that, with certain exceptions (lymphomas, testicular cancer, choriocarcinoma, and others), combination chemotherapy can improve response rates but with only modest or incremental improvement in survival and at the cost of significantly increase in toxicity (2, 3). Therefore, while combination chemotherapy is the norm for localized tumor, sequential therapy with single agent chemotherapy may be preferred for metastatic disease (4, 5).
Besides stage, the location of tumor can also influence the decision for chemotherapy. For example, while endocrine therapy (such as tamoxifen or an aromatase inhibitor) is the mainstay for management of metastatic hormone receptor (HR) positive breast cancer, chemotherapy is preferred among patients who have a widespread visceral disease where rapid control of disease burden is needed.
The location of tumor can influence the decision for adjunctive therapy. Patients with bone metastasis routinely get bone strengthening such as bisphosphonates, in additional to chemotherapy. These agents have been shown to improve bone pain and reduce risk of pathological fractures among patients with bone metastasis (6).
Other factors such as social support systems, economic considerations, and cultural attitudes may also influence the choice of therapy for an individual, and need to be carefully weighed.
2. Organ dysfunction
While patients receiving any medication require careful assessment of organ function, particularly hepatic and renal function, the assessment is particularly important for those receiving chemotherapy due to the narrow therapeutic window and potential for significant toxicity. For example, administering a regular dose of a chemotherapeutic ...