Chapter 081. Principles of Cancer Treatment (Part 1)

Harrisons Internal Medicine Chapter 81. Principles of Cancer TreatmentPrinciples of Cancer Treatment: Introduction The goal of cancer treatment is first to eradicate the cancer. If this primary goal cannot be accomplished, the goal of cancer treatment shifts to palliation, the amelioration of symptoms, and preservation of quality of life while striving to extend life. The dictum primum non nocere is not the guiding principle of cancer therapy. When cure of cancer is possible, cancer treatments may be undertaken despite the certainty of severe and perhaps life-threatening toxicities. Every cancertreatment has the potential to cause harm, and treatment may...
Nội dung trích xuất từ tài liệu:
Chapter 081. Principles of Cancer Treatment (Part 1) Chapter 081. Principles of Cancer Treatment (Part 1) Harrisons Internal Medicine > Chapter 81. Principles of CancerTreatment Principles of Cancer Treatment: Introduction The goal of cancer treatment is first to eradicate the cancer. If this primarygoal cannot be accomplished, the goal of cancer treatment shifts to palliation, theamelioration of symptoms, and preservation of quality of life while striving toextend life. The dictum primum non nocere is not the guiding principle of cancertherapy. When cure of cancer is possible, cancer treatments may be undertakendespite the certainty of severe and perhaps life-threatening toxicities. Every cancertreatment has the potential to cause harm, and treatment may be given thatproduces toxicity with no benefit. The therapeutic index of many interventions isquite narrow, and most treatments are given to the point of toxicity. Conversely,when the clinical goal is palliation, careful attention to minimizing the toxicity ofpotentially toxic treatments becomes a significant goal. Irrespective of the clinicalscenario, the guiding principle of cancer treatment should be primum succerrere,first hasten to help. Radical surgical procedures, large-field hyperfractionatedradiation therapy, high-dose chemotherapy, and maximum tolerable doses ofcytokines such as interleukin (IL) 2 are all used in certain settings where 100% ofthe patients will experience toxicity and side effects from the intervention and onlya fraction of the patients will experience benefit. One of the challenges of cancertreatment is to use the various treatment modalities alone and together in a fashionthat maximizes the chances for patient benefit. Cancer treatments are divided into four main types: surgery, radiationtherapy (including photodynamic therapy), chemotherapy (including hormonaltherapy and molecularly targeted therapy), and biologic therapy (includingimmunotherapy and gene therapy). The modalities are often used in combination,and agents in one category can act by several mechanisms. For example, cancerchemotherapy agents can induce differentiation, and antibodies (a form ofimmunotherapy) can be used to deliver radiation therapy. Surgery and radiationtherapy are considered local treatments, though their effects can influence thebehavior of tumor at remote sites. Chemotherapy and biologic therapy are usuallysystemic treatments. Oncology, the study of tumors including treatmentapproaches, is a multidisciplinary effort with surgical-, radiotherapy-, and internalmedicine–related areas of expertise. Treatments for patients with hematologicmalignancies are often shared by hematologists and medical oncologists. In many ways, cancer mimics an organ attempting to regulate its owngrowth. However, cancers have not set an appropriate limit on how much growthshould be permitted. Normal organs and cancers share the property of having (1) apopulation of cells in cycle and actively renewing and (2) a population of cells notin cycle. In cancers, cells that are not dividing are heterogeneous; some havesustained too much genetic damage to replicate but have defects in their deathpathways that permit their survival, some are starving for nutrients and oxygen,and some are out of cycle but poised to be recruited back into cycle and expand ifneeded (i.e., reversibly growth–arrested). Severely damaged and starving cells areunlikely to kill the patient. The problem is that the cells that are reversibly not incycle are capable of replenishing tumor cells physically removed or damaged byradiation and chemotherapy. These include cancer stem cells, whose properties arebeing elucidated. The stem cell fraction may define new targets for therapies thatwill retard their ability to reenter the cell cycle. Tumors follow a Gompertzian growth curve (Fig. 81-1); the growthfraction of a neoplasm starts at 100% with the first transformed cell and declinesexponentially over time until at the time of diagnosis, with a tumor burden of 1–5x 109 tumor cells, the growth fraction is usually 1–4%. Thus, peak growth rateoccurs before the tumor is detectable. A key feature of a successful tumor is theability to stimulate the development of a new supporting stroma throughangiogenesis and production of proteases to allow invasion through basementmembranes and normal tissue barriers (Chap. 80). Specific cellular mechanisms promote entry or withdrawal of tumor cellsfrom the cell cycle. For example, when a tumor recurs after surgery orchemotherapy, frequently its growth is accelerated and the growth fraction of thetumor is increased. This pattern is similar to that seen in regenerating organs.Partial resection of the liver ...