Cisplatin Health Dictionary

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

Oöphoritis (infection of the ovaries) rarely occurs alone, except in viral infections such as mumps. Usually it is associated with infection of the FALLOPIAN TUBES (SALPINGITIS). It may occur as a complication of a miscarriage, a therapeutic abortion, or the birth of a baby. Cases not associated with pregnancy typically result from sexual activity: the most common organisms involved are Chlamydia, E. coli, and Neisseria gonorrhoea. Cervical swabs should be sent for culture and analgesics given, together with the appropriate antibiotics.

Failure of OVULATION is the cause of INFERTILITY in around a third of couples seeking help with conception. It may also lead to menstrual problems (see MENSTRUATION), such as an irregular menstrual cycle or MENORRHAGIA. An uncommon cause of failure of ovulation is POLYCYSTIC OVARY SYNDROME, often associated with acne, hirsutism, and obesity. Treatment depends on the symptoms. Early ovarian failure is the cause of premature MENOPAUSE. Treatment consists of hormone replacement therapy using a combination of oestrogen and progestogen.

Ovarian cysts (for example, follicular cysts) result from ovulation. They may be symptomless but sometimes cause abdominal pain, pain during intercourse or disturbances in menstruation. Twisting or rupture can cause severe pain, pyrexia (fever) and nausea, and explorative surgery – endoscopic laparotomy – may be needed to establish a diagnosis (symptoms of ECTOPIC PREGNANCY are similar). The ovary may have to be removed. Simple cysts often disappear of their own accord but a large cyst can cause pressure on surrounding structures and therefore should be surgically removed.

In young women the most common benign tumour is a dermoid cyst, while in older women, ?broma (see under UTERUS, DISEASES OF) is more common. All benign tumours should be removed surgically in order to be sure they are not malignant.

Malignant tumours may be primary (arising in the ovary) or secondary (metastases from a cancer developing in another organ). Treatment depends upon the site and type of the primary tumour.

Around 5,000 women a year are diagnosed as having ovarian cancer in England and Wales. Unfortunately it is not readily detected in its early stages; around 85 per cent of women do not see a doctor until after the tumour has spread. Early tumours present with symptoms similar to benign tumours, while late ones present with abdominal distension, pain and vague gastrointestinal symptoms. The disease is most common in menopausal women. Earlier diagnosis and treatment can be achieved by ULTRASOUND screening. Treatment is surgical, aimed at totally removing the tumour mass. Nowadays RADIOTHERAPY is only used for palliation. CHEMOTHERAPY is often given to patients with ovarian metastases, or who have residual disease after surgery. The most active cytotoxic agent is the taxane, PACLITAXEL – especially when it is combined with cisplatin.... ovaries, diseases of

n. a drug that differs in minor ways in molecular structure from its parent compound. Examples are *calcipotriol (an analogue of vitamin D), *betahistine (an analogue of histamine), and the *gonadorelin analogues. Useful analogues of existing drugs are either more potent or cause fewer side-effects. *Carboplatin and *oxaliplatin, for example, are less toxic analogues of *cisplatin.... analogue

n. a derivative of platinum that is used in the treatment of advanced ovarian and lung cancers. It is similar to *cisplatin but has fewer side-effects; in particular, it causes less nausea and nephrotoxicity but more myelosuppression.... carboplatin

A CYTOTOXIC drug of the taxane group (see TAXANES). Given by intravenous transfusion, it is used under specialist supervision for the treatment of ovarian cancer (usually following surgery – see OVARIES, DISEASES OF) with or without CISPLATIN. NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE (NICE) guidance in 2001 also recommended that the drug could be used to treat advanced breast cancer (see BREASTS, DISEASES OF) where initial cytotoxic therapy had failed or could not be used. Its use as ?rst-line treatment is limited to clinical trials.

Side-effects of paclitaxel include hypersensitivity, MYELOSUPPRESSION, cardiac ARRHYTHMIA and peripheral NEUROPATHY. Only a minority of patients respond to the drug, but when it works the results are often long-lasting.... paclitaxel

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

(osteogenic sarcoma) n. a highly malignant tumour arising from within a bone, usually in the *metaphysis of the long bones of the body and especially around the knee and the proximal end of the humerus. It is usually seen in children and adolescents but can occur in adults of all ages, occasionally in association with *Paget’s disease of bone. In children the usual site for the tumour is the leg, particularly the femur. Secondary growths (metastases) are common, most frequently in the lungs (though other sites, such as the liver, may also be involved). The symptoms are usually pain and swelling at the site of the tumour and there is often a history of preceding trauma, although it is doubtful whether this contributes to the cause. Treatment of disease localized to the primary site was traditionally by amputation of the limb; limb-sparing surgery is now possible after *neoadjuvant chemotherapy, with replacement of the diseased bone by a metal prosthesis. Many centres also give *adjuvant therapy in an attempt to kill any microscopic tumour that might have already spread. The drugs used include doxorubicin, cisplatin, vincristine, cyclophosphamide, and methotrexate.... osteosarcoma

n. a third-generation analogue of *cisplatin that is useful in the treatment of gastrointestinal malignancies, particularly advanced colorectal cancer. Administered in combination with fluorouracil and folinic acid, it has less toxic side-effects than cisplatin, although it can cause a typical *peripheral neuropathy exacerbated by cold temperatures.... oxaliplatin

n. a substance that increases the sensitivity of cells to radiation. The presence of oxygen and other compounds with a high affinity for electrons will increase radiosensitivity. Chemotherapy drugs such as fluorouracil and cisplatin can be used concurrently with radiotherapy as radiosensitizers (see chemoradiotherapy).... radiosensitizer

n. a tumour composed of a number of tissues that are not usually found at that site and are derived from all three embryonic *germ layers. Teratomas most frequently occur in the testis and ovary (see dermoid cyst), possibly derived from remnants of embryonic cells that have the ability to differentiate into many types of tissue; in most malignant teratomas, cells from all three *germ layers are present. Malignant teratoma of the testis is found in young men: it is more common in patients with a history of undescended testis. Like *seminoma, it frequently occurs as a painless swelling of one testis (pain is not a good indication that the swelling is benign). Treatment is by *orchidectomy avoiding an incision into the scrotum. The tumour can spread to lymph nodes, lungs, and bone, treatment of which may involve the use of chemotherapy drugs, such as vinblastine, bleomycin, cisplatin, and etoposide, with a high cure rate even in metastatic disease.

Teratomas often produce *alpha-fetoprotein, beta human chorionic gonadotrophin, or both; the presence of these substances (*tumour markers) in the blood is a useful indication of the amount of tumour and the effect of treatment.... teratoma