Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
DaunoXome (NeXstar Pharmaceuticals)
vials containing 50 mg/25 mL concentrated solution
Indication: Kaposi's sarcoma
Kaposi's sarcoma is the most frequent neoplasm affecting homosexual or bisexual men with HIV infection. The patients who develop progressive disease have a poor prognosis. Various regimens of chemotherapy have been used in palliation.
There are obvious problems in giving cytotoxic drugs to patients who already have a suppressed immune system. In an effort to deliver more of the drug to the affected tissues, daunorubicin has been encapsulated in liposomes. These liposomes are 50-80 nm in diameter and are made of cholesterol and distearoylphosphatidylcholine. Encapsulated daunorubicin shows selectivity for tumour tissue in animal models. The intact liposome enters the tumour cells. Its structure is then disrupted to release daunorubicin.
Liposomal daunorubicin has different pharmacokinetics to daunorubicin. It has a higher peak plasma concentration, a smaller volume of distribution and a lower clearance. The exposure following a dose of 80 mg/m2 is approximately 36 times greater than with conventional daunorubicin.
Liposomal daunorubicin has been compared with a combination of doxorubicin, bleomycin and vincristine in the treatment of advanced Kaposi's sarcoma in 227 patients.1 Treatment was given every two weeks until there was a response, the disease progressed or toxicity developed. There was no significant difference in the response rate with 25%of the patients given liposomal daunorubicin having a response (28% in the control group). The median duration of response was similar in both groups. When the data were analysed, 107 of the patients were dead. The median duration of survival was 369 days for patients given liposomal daunorubicin and 342 days for the combination treatment. The researchers estimated survival to be 53% at one year for daunorubicin.
Neutropenia occurred in approximately 35% of both treatment groups, but patients given liposomal daunorubicin were more likely to develop severe neutropenia (<500 cells/mm3). More of the patients given liposomal daunorubicin developed opportunistic infections and more required G-CSF.
Care should be taken when infusing the drug as inflammation can occur at the injection site. There is also a need to be alert for allergic reactions.
Daunorubicin is associated with cardiomyopathy and there is no clear evidence that the new formulation will be less toxic. All patients should have their cardiac function assessed.
Neuropathy occurs in 13% of patients. This is significantly less than in patients given daunorubicin, bleomycin and vincristine. Liposomal daunorubicin also has the advantage of causing less alopecia.
- Gill PS, Wernz J, Scadden DT, Cohen P, Mukwaya GM, Haydenvon Roenn J, et al. Randomised phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin and vincristine in AIDS-related Kaposi's sarcoma. J Clin Oncol 1996;14:2353-64.