Chapter 081. Principles of Cancer Treatment (Part 7)

Karnofsky was among the first to champion the evaluation of a chemotherapeutic agents benefit by carefully quantitating its effect on tumor size and using these measurements to objectively decide the basis for further treatment of a particular patient or further clinical evaluation of a drugs potential. A partial response (PR) is defined conventionally as a decrease by at least 50% in a tumors bidimensional area; a complete response (CR) connotes disappearance of all tumor; progression of disease signifies an increase in size of existing lesions by 25% from baseline or best response or development of new lesions; and "stable"...
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Chapter 081. Principles of Cancer Treatment (Part 7) Chapter 081. Principles of Cancer Treatment (Part 7) Karnofsky was among the first to champion the evaluation of achemotherapeutic agents benefit by carefully quantitating its effect on tumor sizeand using these measurements to objectively decide the basis for further treatmentof a particular patient or further clinical evaluation of a drugs potential. A partialresponse (PR) is defined conventionally as a decrease by at least 50% in a tumorsbidimensional area; a complete response (CR) connotes disappearance of alltumor; progression of disease signifies an increase in size of existing lesions by>25% from baseline or best response or development of new lesions; and stabledisease fits into none of the above categories. Newer evaluation systems utilizeunidimensional measurement, but the intent is similar in rigorously definingevidence for the activity of the agent in assessing its value to the patient. If cure is not possible, chemotherapy may be undertaken with the goal ofpalliating some aspect of the tumors effect on the host. Common tumors that maybe meaningfully addressed with palliative intent are listed in Table 81-1, E.Usually, tumor-related symptoms may manifest as pain, weight loss, or some localsymptom related to the tumors effect on normal structures. Patients treated withpalliative intent should be aware of their diagnosis and the limitations of theproposed treatments, have access to supportive care, and have suitableperformance status, according to assessment algorithms such as the onedeveloped by Karnofsky or by the Eastern Cooperative Oncology Group (ECOG).ECOG performance status 0 (PS0) patients are without symptoms; PS1 patientshave mild symptoms not requiring treatment; PS2, symptoms requiring sometreatment; PS3, disabling symptoms, but allowing ambulation for >50% of theday; PS4, ambulation chemotherapeutic approaches at some point in the natural history, palliative careor hospice-based approaches, with meticulous and ongoing attention to symptomrelief and with family, psychological, and spiritual support, should receiveprominent attention as a valuable therapeutic plan (Chap. 11). Optimizing thequality of life rather than attempting to extend it becomes a valued intervention.Patients facing the impending progression of disease in a life-threatening wayfrequently choose to undertake toxic treatments of little to no potential value, andsupport provided by the primary caregiver in accessing palliative and hospice-based options can be critical in providing a basis for patients to make sensiblechoices. Cancer Drugs: Overview and Principles for Use Cancer drug treatments are of four broad types. Conventionalchemotherapy agents were historically derived by the empirical observation thatthese small molecules (generally with molecular weight action of, e.g., oncogene products, loss of cell cycle inhibitors, or loss of cell deathregulation, and have acquired the capacity to replicate chromosomes indefinitely,invade, metastasize, and evade the immune system. Targeted therapies seek tocapitalize on the biology behind the aberrant cellular behavior as a basis fortherapeutic effects. Hormonal therapies (the first form of targeted therapy)capitalize on the biochemical pathways underlying estrogen and androgen functionand action as a therapeutic basis for approaching patients with tumors of breast,prostate, uterus, and ovarian origin. Biologic therapies are often macromoleculesthat have a particular target (e.g., antigrowth factor or cytokine antibodies) or mayhave the capacity to orchestrate or regulate the host immune response to kill tumorcells. Thus, biologic therapies include not only antibodies but cytokines and genetherapies. The usefulness of any drug is governed by the extent to which a given dosecauses a useful result (therapeutic effect; in the case of anticancer agents, toxicityto tumor cells) as opposed to a toxic effect. The therapeutic index is the degree ofseparation between toxic and therapeutic doses. Really useful drugs have largetherapeutic indices, and this usually occurs when the drug target is expressed inthe disease-causing compartment as opposed to the normal compartment.Classically, selective toxicity of an agent for an organ is governed by theexpression of an agents target or by differential accumulation into or eliminationfrom compartments where toxicity is experienced or ameliorated, respectively.Currently used chemotherapeutic agents have the unfortunate property that theirtargets are present in both normal and tumor tissues. Therefore, they haverelatively narrow therapeutic indices.