2 Clinical need and practice
2.1 Ovarian cancer is a significant cause of early death, resulting in approximately 5000 deaths in the UK each year.
2.2 Early stages of the disease are often asymptomatic, and as a result most women are diagnosed with advanced disease. This gives a relatively poor prognosis, and 5-year survival rates are reported to be around 30% in the UK and up to 40% in some European countries.
2.3 Surgery is usually the first intervention used to treat the disease. However, in most women it is not possible to remove the tumour completely. Radiotherapy is usually of limited effectiveness and has side-effects on other abdominal organs.
2.4 Platinum-based chemotherapy has been the established therapy in ovarian cancer for some time. However, as research evidence emerged, paclitaxel (Taxol) was added in combination with platinum. It is estimated that 75% of women with ovarian cancer currently receive a paclitaxel/platinum combination as first-line therapy.
2.5 Although most patients (70% to 80%) initially respond to first-line chemotherapy, most responders eventually relapse (55% to 75% within 2 years). Responses can occur when first-line chemotherapy is repeated for a second and sometimes a third time, although they occur proportionately less frequently and do not last as long. A complete response is defined as malignant disease not detectable for at least 4 weeks, and a partial response is defined as tumour size reduced by at least 50% for more than 4 weeks.
2.6 Women who initially respond to first-line therapy are also more likely to respond to second and subsequent courses of therapy. The two factors shown to be predictive of second and subsequent response to first-line therapy are the length of the progression-free interval and the extent of the relapse (that is the number of tumour sites involved and their volume). Current best practice for women who initially respond to first-line therapy is to give second and possibly subsequent courses of the same treatment at some point.
2.7 Once re-treatment with first-line therapies has failed, second-line therapies can be offered. These may alleviate symptoms, but may also prolong survival. At the same time, however, they are likely to have a different range of adverse effects.
2.8 Seven chemotherapy agents are licensed for second-line treatment of ovarian cancer: paclitaxel, carboplatin, chlorambucil, treosulfan, hexamethylmelamine (altretamine), topetecan, and pegylated liposomal doxorubicin hydrochloride (PLDH).
2.9 Choice of second-line therapy is influenced by the effectiveness of the different agents and the patient's response to first-line therapy regimens.
2.10 In May 2000, the National Institute for Clinical Excellence issued the following guidance.
Paclitaxel in combination with a platinum-based therapy (cisplatin or carboplatin) should be the standard initial therapy for patients with ovarian cancer following surgery.
The use of paclitaxel/platinum combination therapy in the treatment of recurrent (or resistant) ovarian cancer is recommended if the patient has not previously received this drug combination. If the patient has already received both drugs, the combination of paclitaxel and platinumbased therapy in recurrent (or resistant) ovarian cancer is not recommended, outside the context of clinical trials.
It was recommended that the NICE guidance should be reviewed once full results from a further study (ICON3) were available. The present document has been prepared as part of that review.