Reduction in doxorubicin toxicity following liposomal delivery

During a Phase I clinical trial ofliposome-entrapped doxorubicin ('Lip-Dox') in patients with hepatic metastatic disease, detailed attention is being paid to toxicity and pharmacokinetics of the drug as well as a preliminary evaluation of clinical efficacy. Initial data show that weekly intravenous doses of 15 mg/m 2 are very well tolerated. 'Lip-Dox' is administered through a syringe attached to a 45 mm, 18G (Venflon 2) intravenous cannula delivering 0.9% saline as a fast-flowing drip. When patients are given their first 'Lip-Dox' dose this drip is removed 30 min after the infusions; a similar, though slow running, drip and three-way tap is placed in the opposite wrist for taking blood samples for pharmacokinetic study. By careful back-washing at each sampling, this procedure can be used for up to 12 h without the need for heparin. The same vein may be used for repeated administrations of'Lip-Dox' without any evidence of damage. One patient has completed three courses of four 'Lip-Dox' weekly infusions and there has been no evidence of any nausea, buccal ulceration or hair loss. White blood cell (WBC) and platelet counts have not been lowered, nor has serum bilirubin been raised over the period of therapy. The sole 'reaction' to date has been a mild, transient pyrexia 12 h after the ninth and twelfth doses. Two other patients have undergone single courses of'Lip-Dox' at 15 mg/m 2 and a similar instance of transient pyrexia alter the first dose was noted in one of these patients. Since the above summary was prepared for the meeting in April, four patients have been recruited for treatment at 20 mg/m 2. The first such patient experienced mild, temporary myelosuppression (nadir 1800 WBC/mm 3) after the third 'Lip-Dox' infusion. Treatment was delayed 1 week, after which time the WBC count had returned to the pre-treatment level. This patient has subsequently undertaken three further courses of'Lip-Dox' weekly injections. The second patient has successfully completed two courses of'Lip-Dox' while the third and fourth have completed single courses of four 'Lip-Dox' injections. A single instance of transient pyrexia 12 h after the first injection was noted by one of the patients. There has been no evidence of phlebitis nor of alopecia, buccal ulceration, diarrhoea, nausea nor