Comment

Many uncontrolled trials, particularly in AIDS-related KS, have suggested a response rate, in terms of reduction in number and/or size of lesions, to a variety of cytotoxic agents including bleomycin, vinca alkaloids, etoposide and paclitaxel. Evaluation of earlier studies is made difficult by variation in the definitions used to stage disease and to assess response to therapy. The adoption of standardised ACTG criteria for staging and assessing response to treatment has made it easier to compare studies and should be used in future therapeutic trials.10

One small RCT suggested that combination chemotherapy with ABV chemotherapy is more effective than single-agent standard doxorubicin. Subsequently, three large RCTs have provided good evidence, using ACTG criteria to assess response, that liposomal anthracyclines are at least as effective in AIDS-related cutaneous KS as standard ABV or BV combination chemotherapy.60-62 The two RCTs that specifically compared PLD with ABV or BV chemotherapy provide good evidence that PLD is more effective than standard combination chemotherapy.61,62 The better toxicity profiles found in all three studies, associated with less frequent early termination of therapy because of adverse events, also favours the use of liposomal chemotherapy over standard combination chemotherapy. The addition of bleomycin and vincristine to liposomal doxorubicin is unlikely to be of benefit.

Although overall response rates to PLD are higher than for ABV or BV chemotherapy, the median duration of response is similar. In the RCT comparing PLD with ABV chemotherapy, the median duration of response was 90 days and 92 days, respectively.61 In the RCT comparing PLD with BV chemotherapy, the median duration of response was 142 days and 123 days, respectively, but the difference was not statistically significant.62

Although we found no RCTs directly comparing the two liposomal drugs, the response rates for patients with advanced AIDS-related KS appear to be higher with liposomal doxorubicin than with daunorubicin. There have been no studies of sequential chemotherapy. Newer single-agent cytotoxic therapies such as paclitaxel, vinorelbine and gemcitabine should be compared with liposomal anthracyclines in large phase III studies.

0 0

Post a comment