Efficacy

A systematic review found no RCTs testing systemic therapy against best supportive care.3 It is doubtful that such a trial will ever be done, given that there is great deal of evidence for albeit modest activity in patients with advanced disease.

Dacarbazine (DTIC, di-methyl triazeno imidazole carboxamide) has been the most tested single chemotherapeutic agent. With current antiemetics, it is well tolerated and is considered by many to be the "gold standard" against which other therapies should be tested.4-7 When used alone it gives partial response rates of about 20% (>50% regression for at least 4 weeks), complete responses (complete regression of measurable disease for at least 4 weeks) in 5-10% and long-term remissions in fewer than 2% of patients. It is usually given intravenously at 850-1000 mg/m2 on day 1 every 3 weeks or 200 mg/m2 on days 1-5 every 4 weeks. It is given with intravenous or oral 5-HT3 antagonist or dexamethasone as anti-emetics.

Temozolamide is a novel oral alkylating agent with a broad spectrum of antitumour activity. It has 100% oral bioavailability and good penetration of the blood-brain barrier and cerebrospinal fluid. Its efficacy is at least equal to that of dacarbazine in metastatic MM, median survival being 7-7 months with temozolamide

Table 24.1 Survival of patients with metastatic malignant melanoma

Prognostic factor

Median survival (months)

Number of metastatic sites

1

7

2

4

3

2

Site of metastatic disease

Cutaneous nodes

12-5

Lung

11

Brain, liver, bone

2-6

and 6-4 months with dacarbazine (hazard ratio 1-18, CI 0-92-1-52), and with improvement in some parameters of quality of life.8 Given its similar mechanism of action to dacarbazine, it is not surprising that response rates are fairly similar but in a disease with such a poor prognosis, ease of administration and quality of life are clearly very important.

of the false promise of such combinations was seen when a response rate of 55% was reported for the combination of dacarbazine, cisplatin, carmustine and tamoxifen,11 which has become known as the Dartmouth regimen. However, a multicentre randomised trial comparing this regimen with single-agent dacarbazine found no survival advantage and only a small, non-significant increase in tumour response in an intention-to-treat analysis (see Table 24.2).9

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