Neoplastic disease
Neoplastic disease disease means the new growth of a tumour, which may be innocent or malignant. It arises at any age, in any site of the body. Both innocent (benign) growths and those which are malignant (non-benign or cancer) can arise from most tissues and their cell structure resembles that of the tissue of origin. An innocent growth causes disease by its size; it grows slowly and may remain stationary in size for many years. It may be brought to the patient's notice by the appearance of a visible lump or by symptoms from pressure on some other organ or tissue. It does not eat its way into other tissues by 'invasion'. It does not recur if it is removed, and it does not spread by a process of seeding. A malignant growth on the other hand, increases at a variable rate but relentlessly. It erodes and invades surrounding tissue, forming ulcers, craters, abscesses and, in bone, fractures. Malignant disease by its attack on blood vessels frequently presents as severe haemorrhage. It spreads to neighbouring lymph glands; by the blood stream it is
seeded to other parts of the body. It affects the whole patient, produces debility, anaemia and ultimately death. Innocent tumours may change their nature and become malignant after many years of lying dormant. This risk is a good reason for the removal of apparently harmless tumours. Neoplasms are parasites. They live at the expense of their host and serve no purpose. Certain tumours produce cells which can function like their parent cell, as for instance in producing hormones. A tumour of the pituitary or pancreas may so alter the patient's metabolism that the e ndocrine change is the first feature to arouse suspicion that a neoplasm is present.
Types
There are several different types of cancers:
·Carcinomas are cancers that arise in the epithelium (the layers of cells covering the body's surface and lining the internal organs and various glands). Ninety percent of human cancers fall into this category. Carcinomas can be subdivided into two types: adenocarcinomas and squamous cell carcinomas. Adenocarcinomas are cancers that develop in an organ or a gland, while squamous cell carcinomas refer to cancers that originate in the skin.
·Melanomas also originate in the skin, usually in the pigment cells (melanocytes).
·Sarcomas are cancers of the supporting tissues of the body, such as bone, muscle and blood vessels.
·Cancers of the blood and lymph glands are called leukemias and lymphomas respectively.
·Gliomas are cancers of the nerve tissue.
Symptoms
Cancer is a progressive disease, and goes through several stages with varying symptoms. Some symptoms are produced early and may occur due to a tumor that is growing within an organ or a gland. As the tumor grows, it may press on the nearby nerves, organs, and blood vessels. Despite the fact that there are several hundred different types of cancers, producing very different symptoms, the ACS has established the following seven symptoms as possible warning signals of cancer:
·changes in the size, color, or shape of a wart or a mole
·a sore that does not heal
·persistent cough, hoarseness, or sore throat
·a lump or thickening in the breast or elsewhere
·unusual bleeding or discharge
·chronic indigestion or difficulty in swallowing
·any change in bowel or bladder habits
Treatment
Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.
Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods.
Chemotherapy: There are a number of strategies in the administration of chemotherapeutic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms.
Combined modality chemotherapy is the use of drugs with other cancer treatments, such as radiation therapy or surgery. Most cancers are now treated in this way. Combination chemotherapy is a similar practice which involves treating a patient with a number of different drugs simultaneously. The drugs differ in their mechanism and side effects.
The majority of chemotherapeutic drugs can be divided in to alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents. All of these drugs affect cell division or DNA synthesis and function in some way.
Some newer agents don't directly interfere with DNA. These include monoclonal antibodies and the new tyrosine kinase inhibitors e.g. imatinib mesylate (Gleevec or Glivec), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors).
In addition, some drugs may be used which modulate tumor cell behaviour without directly attacking those cells. Hormone treatments fall into this category of adjuvant therapies.
Alkylating agents: add alkyl groups to many electronegative groups under conditions present in cells. Cisplatin and carboplatin, as well as oxaliplatin are alkylating agents.
Other agents are mechlorethamine, cyclophosphamide, chlorambucil. They work by chemically modifying a cell's DNA.
Anti-metabolites: masquerade as purine ((azathioprine, mercaptopurine)) or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division by preventing azathioprine, mercaptopurine or pyrimidine to synthesize DNA. They also affect RNA synthesis. Due to their efficiency, these drugs are the most widely used cytostatics.
Plant alkaloids: These alkaloids are derived from plants and block cell division by preventing microtubule function. Microtubules are vital for cell division and without them it can not occur. The main examples are vinca alkaloids and taxanes.
Vinca alkaloids bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules (M phase of the cell cycle).
·Vincristine
·Vinblastine
·Vinorelbine
·Vindesine
[edit] Podophyllotoxin (L01CB)
Podophyllotoxin is a plant-derived compound used to produce two other cytostatic drugs, etoposide and teniposide. They prevent the cell from entering the G1 phase (the start of DNA replication) and the replication of DNA (the S phase). The exact mechanism of its action is not yet known.
Taxanes :The prototype taxane is the natural product paclitaxel, originally known as Taxol and first derived from the bark of the Pacific Yew tree. Docetaxel is a semi-synthetic analogue of paclitaxel. Taxanes enhance stability of microtubules, preventing the separation of chromosomes during anaphase.
Monoclonal antibodies work by targeting tumour specific antigens, thus enhancing the host's immune response to tumour cells to which the agent attaches itself. Examples are trastuzumab (Herceptin), cetuximab, and rituximab (Rituxan or Mabthera). Bevacizumab (Avastin) is a monoclonal antibody that does not directly attack tumor cells but instead blocks the formation of new tumor vessels.
Hormonal therapy
Several malignancies respond to hormonal therapy. Strictly speaking, this is not chemotherapy. Cancer arising from certain tissues, including the mammary and prostate glands, may be inhibited or stimulated by appropriate changes in hormone balance.
·Steroids (often dexamethasone) can inhibit tumour growth or the associated edema (tissue swelling), and may cause regression of lymph node malignancies. Dexamethasone is also an antiemetic, so it may be used with cytotoxic chemotherapy even if it has no direct effect on the cancer.
·Prostate cancer is often sensitive to finasteride, an agent that blocks the peripheral conversion of testosterone to dihydrotestosterone.
·Breast cancer cells often highly express the estrogen and/or progesterone receptor. Inhibiting the production (with aromatase inhibitors) or action (with tamoxifen) of these hormones can often be used as an adjunct to therapy.
·Gonadotropin-releasing hormone agonists (GnRH), such as goserelin possess a paradoxical negative feedback effect followed by inhibition of the release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone), when given continuously.
Dosage of chemotherapy can be difficult: if the dose is too low, it will be ineffective against the tumor, while at excessive doses the toxicity (side-effects, neutropenia) will be intolerable to the patient. This has led to the formation of detailed "dosing schemes" in most hospitals, which give guidance on the correct dose and adjustment in case of toxicity. In immunotherapy, they are in principle used in smaller dosages than in the treatment of malignant diseases.
In most cases, the dose is adjusted for the patient's body surface area, a measure that correlates with blood volume. The BSA is usually calculated with a mathematical formula or a nomogram, using a patient's weight and height, rather than by direct measurement.
side effects
In particularly large tumors, such as large lymphomas, some patients develop tumor lysis syndrome from the rapid breakdown of malignant cells. Although prophylaxis is available and is often initiated in patients with large tumors, this is a dangerous side-effect which can lead to death if left untreated.
A proportion of patients report fatigue or non-specific neurocognitive problems, such as an inability to concentrate; this is sometimes called post-chemotherapy cognitive impairment, colloquially referred to as "chemo brain" by patients' groups.[9]
Specific chemotherapeutic agents are associated with organ-specific toxicities, including cardiovascular disease (e.g., doxorubicin), interstitial lung disease (e.g., bleomycin) and occasionally secondary neoplasm (e.g. MOPP therapy for Hodgkin's disease).