“The contents and aesthetics of European Oncology & Haematology are very good and together with impressive well selected...
Doxil® (Caelyx®)—Pegylated Liposomal Doxorubicin
Doxorubicin is a widely used cancer chemotherapeutic with significant side effects that include myelosuppression and cardiotoxicity. Lipid encapsulation of the drug was expected to decrease these toxic side effects, since liposomes can penetrate endothelial lesions found in the neovasculature of tumors but not in normal blood vessels. Supporting the fact that liposomal doxorubicin targets the tumor more selectively due to its leaky vasculature, Vaage and co-workers demonstrated that—compared with the aqueous formulation—25 times more liposomal doxorubicin accumulated in tumors.2 As predicted, lipid encapsulation also decreased myelosuppression and cardiotoxicity, but, unfortunately, led to increased mucosal and skin toxicities. Liposomal doxorubicin is known as Doxil® in the US and Caelyx® in Canada. Doxil is currently approved for the treatment of AIDS-related Kaposi sarcoma and ovarian cancer.
Doxil as a Single Treatment Regimen for Hormone-refractory Prostate Cancer
A literature search identified six clinical trials in which liposomal doxorubicin was used as a single agent against prostate cancer. In the first pharmacokinetic study, published in 2000, 15 patients with hormonerefractory prostate cancer (HRPC) received Doxil either at 45mg/m2 every three weeks or 60mg/m2 every four weeks.3 A common side effect was stomatitis, which was higher among patients receiving the 60mg/m2 regimen, whereas hand–foot syndrome was more frequent among patients receiving the 45mg/m2 regimen. The toxicity indicated that neither dose regimen was tolerable, but a modest activity of Doxil against HRPC justified future studies. The modest effect of Doxil as a single agent against HRPC was confirmed in subsequent studies (see Table 1). In one small study no clinical response was observed, but the authors suggested that a phase II trial with 20mg/m2 liposomal doxorubicin was warranted.4 However, even this dose may have been insufficient to elicit a biochemical response, since the only studies that report a decrease in prostate-specific antigen (PSA) (>50%) administered Doxil at concentrations of 40mg/m2 or greater once every four weeks.3,5–8 This is illustrated in the largest phase II study, which was conducted in Germany.6 Since an optimal schedule had not been established, Doxil was administered at either 25mg/m2 every two weeks for 12 cycles or 50mg/m2 every four weeks for six cycles. Interestingly, while all patients received Doxil at 12.5mg/m2/week, only the group treated with the less frequent but higher dose had a biochemical response (see Table 1). Studies also found that PSA is not always a reliable measure of treatment response. For example, in some patients PSA increased after initiation of Doxil treatment, but subsequently decreased to below levels at treatment initiation.5,6 The initial increase in PSA can easily be misinterpreted as treatment failure. On the other hand, a decrease in PSA may occur while the disease is progressing, and is possibly indicative of a change toward a low-PSA-producing tumor.7