Phase I study of Caelyx (doxorubicin HCL, pegylated liposomal) in recurrent or metastatic head and neck cancer

Background: Pegylated liposome technology represents a favourable drug-carrier system, since stealth liposomal drugs have a reduced clearance with prolonged circulation half-life and selective drug accumulation in tissues with increased vascular permeability, such as tumor tissues. Caelyx is a pegylated liposome containing doxorubicin, which has been developed to target drug delivery to cancer cells, thus reducing toxicities. Biodistribution studies have shown a selective tumor uptake in patients with advanced head and neck cancer (HNC), thus justifying the present phase I study. Patients and methods: Patients with recurrent or metastatic HNC were treated with Caelyx administered at the starting dose of 30 mg/m(2) every three weeks and escalated by 5 mg/m(2) per step. Dose escalation was stopped if more than a third of patients of a given cohort had dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia, grade 3 febrile neutropenia, grade 3 thrombocytopenia with bleeding, grade 3 non-hematologic toxicity (except for nausea and alopecia), or > 2 week delay in chemotherapy recycling. The above dose level was defined as maximum tolerated dose (MTD) and the dose level immediately below was recommended for phase II evaluation. Response was evaluated after three courses of chemotherapy. Results: Twenty-four patients were treated at five dose levels. At 50 mg/m(2), three out of six patients had grade 3 stomatitis; therefore, this level was defined as MTD and 45 mg/m(2) was the selected dose for phase II. Stomatitis occurred in 11 patients across all dose levels, considering all delivered cycles. Neutropenia occurred in 10 of 24 patients, but reached grade 4 in only 2 patients at fourth dose level. Skin toxicity, mainly appearing in the form of palmar-plantar erythrodysestesia, was the most frequent toxicity, occurring in 14 patients. Other side effects were mild. One complete response (4%) and seven partial responses (29%) were observed, for an overall response rate of 33% (95% confidence interval (95% CI): 16%-55%). Conclusions: Caelyx is a safe and promising new treatment in HNC, that deserves further evaluation both alone and integrated within chemo-radiotherapy strategies.