Principles of Cancer Treatment Part 7 Karnofsky was among the first to champion the evaluation of a chemotherapeutic agent's benefit by carefully quantitating its effect on tumor size
Trang 1Chapter 081 Principles of
Cancer Treatment
(Part 7)
Karnofsky was among the first to champion the evaluation of a chemotherapeutic agent's 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 drug's potential A partial response (PR) is defined conventionally as a decrease by at least 50% in a tumor's 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" disease fits into none of the above categories Newer evaluation systems utilize
Trang 2unidimensional measurement, but the intent is similar in rigorously defining evidence 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 of palliating some aspect of the tumor's effect on the host Common tumors that may
be meaningfully addressed with palliative intent are listed in Table 81-1, E
Usually, tumor-related symptoms may manifest as pain, weight loss, or some local symptom related to the tumor's effect on normal structures Patients treated with palliative intent should be aware of their diagnosis and the limitations of the proposed treatments, have access to supportive care, and have suitable
"performance status," according to assessment algorithms such as the one developed by Karnofsky or by the Eastern Cooperative Oncology Group (ECOG) ECOG performance status 0 (PS0) patients are without symptoms; PS1 patients have mild symptoms not requiring treatment; PS2, symptoms requiring some treatment; PS3, disabling symptoms, but allowing ambulation for >50% of the day; PS4, ambulation <50% of the day Only PS0, PS1, and PS2 patients are generally considered suitable for palliative (noncurative) treatment If there is curative potential, even poor-performance status patients may be treated, but their prognosis is usually inferior to that of good-performance patients treated with similar regimens
An important perspective the primary care provider may bring to patients and their families facing incurable cancer is that, given the limited value of
Trang 3chemotherapeutic approaches at some point in the natural history, palliative care
or hospice-based approaches, with meticulous and ongoing attention to symptom
relief and with family, psychological, and spiritual support, should receive prominent attention as a valuable therapeutic plan (Chap 11) Optimizing the quality of life rather than attempting to extend it becomes a valued intervention Patients facing the impending progression of disease in a life-threatening way frequently choose to undertake toxic treatments of little to no potential value, and support provided by the primary caregiver in accessing palliative and hospice-based options can be critical in providing a basis for patients to make sensible choices
Cancer Drugs: Overview and Principles for Use
Cancer drug treatments are of four broad types Conventional
chemotherapy agents were historically derived by the empirical observation that
these "small molecules" (generally with molecular weight <1500 Da) could cause major regression of experimental tumors growing in animals These agents mainly
target DNA structure or segregation of DNA as chromosomes in mitosis Targeted
agents refer to small molecules or "biologicals" (generally macromolecules such
as antibodies or cytokines) designed and developed to interact with a defined molecular target important in either maintaining the malignant state or selectively expressed by the tumor cells As described in Chapter 80, successful tumors have activated biochemical pathways that lead to uncontrolled proliferation through the
Trang 4action of, e.g., oncogene products, loss of cell cycle inhibitors, or loss of cell death regulation, and have acquired the capacity to replicate chromosomes indefinitely, invade, metastasize, and evade the immune system Targeted therapies seek to capitalize on the biology behind the aberrant cellular behavior as a basis for
therapeutic effects Hormonal therapies (the first form of targeted therapy)
capitalize on the biochemical pathways underlying estrogen and androgen function and action as a therapeutic basis for approaching patients with tumors of breast,
prostate, uterus, and ovarian origin Biologic therapies are often macromolecules
that have a particular target (e.g., antigrowth factor or cytokine antibodies) or may have the capacity to orchestrate or regulate the host immune response to kill tumor cells Thus, biologic therapies include not only antibodies but cytokines and gene therapies
The usefulness of any drug is governed by the extent to which a given dose causes a useful result (therapeutic effect; in the case of anticancer agents, toxicity
to tumor cells) as opposed to a toxic effect The therapeutic index is the degree of
separation between toxic and therapeutic doses Really useful drugs have large therapeutic indices, and this usually occurs when the drug target is expressed in the disease-causing compartment as opposed to the normal compartment Classically, selective toxicity of an agent for an organ is governed by the expression of an agent's target or by differential accumulation into or elimination from compartments where toxicity is experienced or ameliorated, respectively
Trang 5Currently used chemotherapeutic agents have the unfortunate property that their targets are present in both normal and tumor tissues Therefore, they have relatively narrow therapeutic indices