Harrison's Internal Medicine Chapter 81. Principles of Cancer Treatment
Principles 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.
Staging As noted in Chap. 77, an important component of patient management is defining the extent of disease. Radiographic and other imaging tests can be helpful in defining the clinical stage; however, pathologic staging requires defining the extent of involvement by documenting the histologic presence of tumor in tissue biopsies obtained through a surgical procedure.
The third volume of the Annals of Traditional Chinese Medicine carries
the theme of Cancer Treatment. Since the commencement of this book
series, the Editorial Board has emphasized its main objective, that is to
help modernize Chinese medicine, thus providing a convenient platform
for all scientists, including those who belong to the traditional camp as
well as members of the modern scientific community who insist on strict
The International Agency for Research on Cancer (IARC, World Health Organization)
[ 1 ] estimated an incidence of 6,617,855 cancers around the world in 2008 with 4,219,626
deaths associated with this disease (IARC 2011).
Principles of Chemotherapy Medical oncology is the subspecialty of internal medicine that cares for and designs treatment approaches to patients with cancer, in conjunction with surgical and radiation oncologists. The core skills of the medical oncologist include the use of drugs that may have a beneficial effect on the natural history of the patient's illness or favorably influence the patient's quality of life. In general, the curability of a tumor is inversely related to tumor volume and directly related to drug dose.
Palliation Surgery is employed in a number of ways for supportive care: insertion of central venous catheters, control of pleural and pericardial effusions and ascites, caval interruption for recurrent pulmonary emboli, stabilization of cancerweakened weight-bearing bones, and control of hemorrhage, among others. Surgical bypass of gastrointestinal, urinary tract, or biliary tree obstruction can alleviate symptoms and prolong survival. Surgical procedures may provide relief of otherwise intractable pain or reverse neurologic dysfunction (cord decompression).
Application to Patients
Radiation therapy can be used alone or together with chemotherapy to produce cure of localized tumors and control of the primary site of disease in tumors that have disseminated. Therapy is planned based on the use of a simulator with the treatment field or fields designed to accommodate an individual patient's anatomic features. Individualized treatment planning employs lead shielding tailored to shape the field and limit the radiation exposure of normal tissue. Often the radiation is delivered from two or three different positions.
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.
Pemetrexed is a novel folate-directed antimetabolite. It is "multitargeted" in that it inhibits the activity of several enzymes, including thymidylate synthetase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase, thereby affecting the synthesis of both purine and pyrimidine nucleic acid precursors. To avoid significant toxicity to the normal tissues, patients receiving pemetrexed should also receive low-dose folate and vitamin B12 supplementation.
The taxanes include paclitaxel and docetaxel. These agents differ from the vinca alkaloids in that the taxanes stabilize microtubules against depolymerization. The "stabilized" microtubules function abnormally and are not able to undergo the normal dynamic changes of microtubule structure and function necessary for cell cycle completion. Taxanes are among the most broadly active antineoplastic agents for use in solid tumors, with evidence of activity in ovarian cancer, breast cancer, Kaposi's sarcoma, and lung tumors.
Table 81-2 Commonly Used Cancer Chemotherapy Agents
Exam ples of Usual Doses
Direct DNA-Interacting Agents
Liver metabolism required
phosphoramide 100 mg/m2 PO qd Common alkylatora Mesna protects Cardiac dose) against Cystitis mustard + acrolein
(high "high-dose" bladder damage
6 mg/m2 IV day
Topical use in cutaneous lymphoma
Vesicant 1 and day 8 Nausea
1–3 mg/m2 qd PO
Diethylstilbestrol (DES) acting as an estrogen at the level of the hypothalamus to downregulate hypothalamic luteinizing hormone (LH) production results in decreased elaboration of testosterone by the testicle. For this reason, orchiectomy is equally as effective as moderate-dose DES, inducing responses in 80% of previously untreated patients with prostate cancer but without the prominent cardiovascular side effects of DES, including thrombosis and exacerbation of coronary artery disease.
Solid Tumors Small-molecule epidermal growth factor (EGF) antagonists act at the ATP binding site of the EGF receptor tyrosine kinase. In early clinical trials, gefitinib showed evidence of responses in a small fraction of patients with non-small cell lung cancer. Side effects were generally acceptable, consisting mostly of rash and diarrhea. Gefitinib was found to have antitumor activity mainly in the subset of patients with tumors containing activating mutations in the EGF receptor.
Antibodies In general, antibodies are not very effective at killing cancer cells. Because the tumor seems to influence the host toward making antibodies rather than generating cellular immunity, it is inferred that antibodies are easier for the tumor to fend off. Many patients can be shown to have serum antibodies directed at their tumors, but these do not appear to influence disease progression. However, the ability to grow very large quantities of high-affinity antibody directed at a tumor by the hybridoma technique has led to the application of antibodies to the treatment of cancer.
The Gale Encyclopedia of Cancer is a medical reference
product designed to inform and educate readers
about a wide variety of cancers, treatments, diagnostic
procedures, side effects, and cancer drugs. The Gale
Group believes the product to be comprehensive, but
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Head and Neck Cancer: Treatment Patients with head and neck cancer can be categorized into three clinical groups: those with localized disease, those with locally or regionally advanced disease, and those with recurrent and/or metastatic disease. Comorbidities associated with tobacco and alcohol abuse can affect treatment outcome and define long-term risks for patients who are cured of their disease.
Nearly one-third of patients have localized disease; that is, T1 or T2 (stage I or stage II) lesions without detectable lymph node involvement or distant metastases.
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.
Antiangiogenic Therapy Understanding the molecular mechanisms that regulate tumor angiogenesis may provide unique opportunities for cancer treatment. Acquired drug resistance of tumor cells due to their high intrinsic mutation rate is a major cause of treatment failure in human cancers. ECs comprising the tumor vasculature are genetically stable and do not share genetic changes with tumor cells; the EC apoptosis pathways are therefore intact.
This book describes a course of cancer growth starting from normal cells to cancerous form and the genomic instability, the cancer treatment as well as its prevention in form of the invention of a vaccine. Some diseases are also discussed in detail, such as breast cancer, leucaemia, cervical cancer, and glioma. Understanding cancer through its molecular mechanism is needed to reduce the cancer incidence.