Chlorambucil Health Dictionary

Alkylating agents are so named because they alkylate or chemically react with certain biochemical entities, particularly those concerned with the synthesis of NUCLEIC ACID. Alkylation is the substitution of an organic grouping in place of another grouping in a molecule.

Alkylating agents are important because they interfere with the growth and reproduction of cells, disrupting their replication. This CYTOTOXIC property is used to retard the division and growth of cancer cells, and alkylating drugs are widely used in the chemotherapy of malignant tumours – often in conjunction with surgery and sometimes with radiotherapy. Unfortunately, troublesome side-effects occur, such as: damage to veins when the drug is given intravenously, with resultant leakage into adjacent tissues; impaired kidney function due to the formation of URIC ACID crystals; nausea and vomiting; ALOPECIA (hair loss); suppression of BONE MARROW activity (production of blood cells); and adverse effects on reproductive function, including TERATOGENESIS. Indeed, cytotoxic drugs must not be given in pregnancy, especially during the ?rst three months. Prolonged use of alkylating drugs, especially when accompanying radiotherapy, is also associated with a sign?cant rise in the incidence of acute non-lymphocytic LEUKAEMIA. Among the dozen or so alkylating drugs in use are CYCLOPHOSPHAMIDE, CHLORAMBUCIL, MELPHALAN, BUSULFAN and THIOTEPA. (See also CHEMOTHERAPY.)... alkylating agents

Cytotoxic means destructive to living cells. Cytotoxic drugs possess anti-cancer properties but also have the potential to damage normal tissue. Their use is twofold: to eliminate a cancer and so prolong life; or to alleviate distressing symptoms, especially in patients whose prospects of a cure are poor. In many cases CHEMOTHERAPY with cytotoxic drugs is combined with surgery, RADIOTHERAPY or both. Chemotherapy may be used initially to reduce the size of the primary TUMOUR (a process called neoadjuvant therapy) before using radiotherapy or surgery to eliminate it. Cytotoxic drugs may also be used as adjuvant treatment to prevent or destroy secondary spread of the primary tumour that has either been removed by surgery or treated with radiotherapy. All chemotherapy causes side-effects: the ONCOLOGIST – a specialist in cancer treatment – has to strike a balance between hoped-for bene?ts and acceptable (for the patient) toxic effects, which include nausea and vomiting, BONE MARROW suppression, ALOPECIA (hair loss) and teratogenic effects (see TERATOGENESIS).

Cytotoxic drugs are used either singly or in combination, when an enhanced response is the aim. Chemotherapy of cancer is a complex process and should be supervised by an oncologist in co-operation with physicians, surgeons, radiotherapists and radiologists as appropriate.

The cytotoxic drugs include:

(1) The alkylating agents which act by damaging DNA, thus interfering with cell reproduction. Cyclophosphamide, ifosfamide, chlorambucil, kelphalan, busulphan, thiotepa and mustine are examples of alkylating agents.

(2) There are a number of cytotoxic antibiotics used in the treatment of cancer – doxorubicin, bleomycin, dactinomycin, mithramycin and amsacrine are examples. They are used primarily in the treatment of acute leukaemia and lymphomas.

(3) Antimetabolites – these drugs combine irreversibly with vital enzyme systems of the cell and hence prevent normal cell division. Methotrexate, cytarabine, ?uorouracil, mercaptopurine and azathioprine are examples.

(4) Another group of cytotoxic drugs are the vinca alkaloids such as vincristine, vinblastine and vindesima.

(5) Platinum compounds such as carboplatin, cisplatin and oxaliplatin are e?ective. All of them are given intravenously, but the latter two tend to have more unpleasant side-effects. Carboplatin and cisplatin are useful in the treatment of solid tumours. Carboplatin, a derivative of cisplatin, is given intravenously in ovarian cancer and in small-cell lung cancer. Better tolerated than cisplatin, the drug causes less nausea and vomiting, nephrotoxicity, neurotoxicity and ototoxicity. Where platinum-containing therapy has failed, intravenous treatment with paclitaxel may be tried. With only a limited success rate, it is relatively toxic and should be carefully supervised; responses, however, are sometimes prolonged.

Also of increasing importance in treating cancer are interferons. These are naturally occurring proteins with complex effects on immunity and cell function. Although toxic, with numerous adverse effects, they have shown some anti-tumour e?ect against certain lymphomas and solid tumours.... cytotoxic

The nitrogen analogues of mustard gas are among the most important ALKYLATING AGENTS used in the treatment of various forms of malignant disease. They include chlormethine, busulphan, chlorambucil and melphalan.... nitrogen mustards

Leukaemia is an umbrella term for several malignant disorders of white blood cells in which they proliferate in a disorganised manner. The disease is also characterised by enlargement of the SPLEEN, changes in the BONE MARROW, and by enlargement of the LYMPH glands all over the body. The condition may be either acute or chronic.

According to the type of cells that predominate, leukaemia may be classi?ed as acute or chronic lymphoblastic leukaemia or myeloid leukaemia. Acute lymphoblastic leukaemia (ALL) is mostly a disease of childhood and is rare after the age of 25. Acute myeloid leukaemia is most common in children and young adults, but may occur at any age. Chronic lymphatic leukaemia occurs at any age between 35 and 80, most commonly in the 60s, and is twice as common in men as in women. Chronic myeloid leukaemia is rare before the age of 25, and most common between the ages of 30 and 65; men and women are equally affected. Around 2,500 patients with acute leukaemia are diagnosed in the United Kingdom, with a similar number annually diagnosed with chronic leukaemia.

Cause Both types of acute leukaemia seem to arise from a MUTATION in a single white cell. The genetically changed cell then goes through an uncontrolled succession of divisions resulting in many millions of abnormal white cells in the blood, bone marrow and other tissues. Possible causes are virus infection, chemical exposure, radiation and genetic background. The cause of chronic lymphocytic leukaemia is not known; the chronic myeloid version may have a genetic background.

Symptoms In acute cases the patient is pale due to anaemia, may have a purpuric rash due to lack of platelets, and may have enlarged lymphatic glands and spleen. The temperature is raised, and the condition may be mistaken for an acute infection (or may ?rst become apparent because the patient develops a severe infection due to a lack of normal white blood cells).

In the chronic type of the disease the onset is gradual, and the ?rst symptoms which occasion discomfort are either swelling of the abdomen and shortness of breath, due to painless enlargement of the spleen; or the enlargement of glands in the neck, armpits and elsewhere; or the pallor, palpitation, and other symptoms of anaemia which often accompany leukaemia. Occasional bleeding from the nose, stomach, gums or bowels may occur, and may be severe. Generally, there is a slight fever.

When the blood is examined microscopically, not only is there an enormous increase in the number of white cells, which may be multiplied 30- or 60-fold, but various immature forms are also found. In the lymphatic form of the disease, most white cells resemble lymphocytes, which, in healthy blood, are present only in small numbers. In the myeloid form, myelocytes, or large immature cells from the bone marrow, which are never present in healthy blood, appear in large numbers, and there may also be large numbers of immature, nucleated erythrocytes.

Treatment This varies according to the type of leukaemia and to the particular condition of the patient. Excellent results are being obtained in the control of ALL using blood transfusions, CHEMOTHERAPY, RADIOTHERAPY and bone-marrow TRANSPLANTATION. In the case of acute leukaemia, the drugs now being used include MERCAPTOPURINE, METHOTREXATE and CYCLOPHOSPHAMIDE. Blood transfusion and CORTICOSTEROIDS play an important part in controlling the condition during the period before a response to chemotherapy can be expected. Chemotherapy has almost completely replaced radiotherapy in the treatment of chronic leukaemia. For the myeloid form, BUSULFAN is the most widely used drug, replaced by hydroxyurea, mercaptopurine, or one of the nitrogen mustard (see NITROGEN MUSTARDS) derivatives in the later stages of the disease. For the lymphatic form, the drugs used are CHLORAMBUCIL, CYCLOPHOSPHAMIDE, and the nitrogen mustard derivatives.

Prognosis Although there is still no guaranteed cure, the outlook in both acute and chronic leukaemia has greatly improved – particularly for the acute form of the disease. Between 70 and 80 per cent of children with acute lymphoblastic leukaemia may be cured; between 20 and 50 per cent of those with acute myeloid leukaemia now have much-improved survival rates. Prognosis of patients with chronic lymphocytic leukaemia is often good, depending on early diagnosis.... leukaemia

any drug that damages or destroys cells: usually refers to those drugs used to treat various types of cancer. There are various classes of cytotoxic drugs, including *alkylating agents (e.g. *chlorambucil, *cyclophosphamide, *melphalan), *antimetabolites (e.g. *fluorouracil, *methotrexate, *mercaptopurine), *anthracycline antibiotics (e.g. *doxorubicin, *daunorubicin, *dactinomycin), *vinca alkaloids, and platinum compounds (e.g. *carboplatin, *cisplatin). Other cytotoxic drugs include *taxanes and *topoisomerase inhibitors, and some *monoclonal antibodies (e.g. *bevacizumab, *trastuzumab) have cytotoxic activity. All these drugs offer successful treatment in some conditions and help reduce symptoms and prolong life in others. Cytotoxic drugs destroy cancer cells by interfering with cell division, but they also affect normal cells, particularly in bone marrow (causing *myelosuppression), hair follicles (causing hair loss), the stomach lining (resulting in severe nausea and vomiting), mouth (causing soreness), and fetal tissue (they should not be taken during the later stages of pregnancy). Dosage must therefore be carefully controlled. See also chemotherapy.... cytotoxic drug

The management of MALIGNANT disease – a major health problem since successful management requires close liaison between the patient, surgeons, physicians, oncologists, haematologists, paediatricians and other specialists. Diagnosis may involve various investigations and often requires a BIOPSY. Once a diagnosis has been established, treatment may involve surgery, radiotherapy or chemotherapy (or various combinations as required) – see below, and main dictionary entries.

Surgery may be most common, and is often the only treatment, for some gastrointestinal tumours, soft-tissue tumours, gynaecological tumours and advanced cancers of the head and neck.

Radiotherapy uses ionising radiation to kill tumour cells. Radiation is by naturally occurring isotopes (see ISOTOPE) or arti?cially produced X-RAYS. Germ-cell tumours (see SEMINOMA; TERATOMA) and malignant lymphomas (see LYMPHOMA) appear to be particularly sensitive to irradiation, and many head and neck tumours, gynaecological cancers, and localised cancers of the PROSTATE GLAND and URINARY BLADDER are curable with radiotherapy. It is also a valuable means of reducing pain from bone metastases (see METASTASIS). Unpleasant side-effects are common: chie?y lethargy, loss of appetite and dry, itchy skin symptoms.

Chemotherapy is also an important treatment in germ-cell tumours (see above); in some forms of LEUKAEMIA and lymphoma; in ovarian cancer (following surgery – see OVARIES, DISEASES OF); and in small-cell lung cancer (although most patients die within 18 months – see LUNGS, DISEASES OF). It is also used in some breast cancers (see BREASTS, DISEASES OF); advanced myeloma (see MYELOMATOSIS); sarcomas (see under CANCER); and some childhood cancers (such as WILMS’ TUMOUR).

More than 20 substances are in common use, the major classes being ALKYLATING AGENTS (e.g. cyclophosphamide, chlorambucil, busul fan); ANTIMETABOLITES (e.g. methotrexate); VINCA ALKALOIDS (e.g. vincristine, vinblastine); and antitumour ANTIBIOTICS (e.g. actinomycin D). Choice of agent and the appropriate regimen requires expert guidance. Common side-effects include nausea and vomiting, bone-marrow suppression and ALOPECIA, with each substance having its own spectrum of unwanted effects.

Good doctor-patient communication, with the sharing of information and bringing the patient into the decision-making process, is vital even if time-consuming and exhausting.

Equally imortant treatment is PALLIATIVE, for example to ensure e?ective pain or nausea control. Common sources of pain in cancer may involve bone, nerve compression, soft tissue, visceral, myofascial, constipation, muscle spasm, low-back pain, joint pain (e.g. capsulitis) and chronic post-operative pain. Patients may be suffering from more than one pain, all of which should be identi?ed. The aim should be to eliminate pain.

There are three rungs of the analgesic ladder; if one rung fails, the next one should be tried:

(1) non-opioid drugs – for example, aspirin, PARACETAMOL, NON-STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS); (2) weak opioids – for example, CODEINE, DIHYDROCODEINE, dextropropoxyphene; (3) strong opioids

– for example, MORPHINE, DIAMORPHINE, buprenorphine. Oral treatment is always preferable, unless prevented by severe vomiting. (See also CANCER; ONCOLOGIST; PAIN; PALLIATIVE CARE.)... oncology

a malignant disease of lymphatic tissue – a form of *lymphoma – usually characterized by painless enlargement of one or more groups of lymph nodes in the neck, axillae (armpits), groin, chest, or abdomen; the spleen, liver, bone marrow, and bones may also be involved. Apart from the enlarging nodes, there may also be weight loss, fever, profuse sweating at night, and itching (known as B symptoms). Hodgkin’s disease is distinguished from other forms of lymphoma by the presence of large binucleate cells (Reed–Sternberg cells) in the affected lymph nodes. Treatment depends on the extent of disease and may include surgery, radiotherapy, drug therapy, or a combination of these. Drugs used in the treatment of the disease include vincristine, procarbazine, prednisolone, chlorambucil, and vinblastine. Many patients can be cured; in the early stages of the disease this may be in the order of 90% or more. [T. Hodgkin (1798–1866), British physician]... hodgkin’s disease

n. cancer of the lymph nodes, including *Hodgkin’s disease and non-Hodgkin’s lymphomas. There is a broad spectrum of malignancy, with prognosis ranging from a few months to many years. The patient usually shows evidence of multiple enlarged lymph nodes and may have constitutional symptoms such as weight loss, fever, and sweating (the so-called ‘B symptoms’). Disease may be widespread, but in some cases is confined to a single area, which may be extranodal (such as the tonsil). Treatment is with drugs such as chlorambucil or combinations of cyclophosphamide, vincristine, and prednisolone, sometimes with the addition of doxorubicin and/or bleomycin; response to these drugs is often dramatic. New *targeted agents are used depending on the expression of cell surface molecules, particularly *rituximab against CD20 in diffuse B-cell lymphoma. Localized disease may be treated with radiotherapy followed by drugs. Patients with non-Hodgkin’s lymphoma who do not respond to chemotherapy may be considered for a bone-marrow transplant.... lymphoma