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-carr ier system, since stealth liposomal drugs have a reduced clearance with pro longed circulation half-life and selective drug accumulation in tissues wit h increased vascular permeability, such as tumor tissues. Caelyx is a pegyl ated liposome containing doxorubicin, which has been developed to target dr ug delivery to cancer cells, thus reducing toxicities. Biodistribution stud ies 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 treate d with Caelyx administered at the starting dose of 30 mg/m(2) every three w eeks and escalated by 5 mg/m(2) per step. Dose escalation was stopped if mo re than a third of patients of a given cohort had dose-limiting toxicity (D LT), which was defined as grade 4 neutropenia or thrombocytopenia, grade 3 febrile neutropenia, grade 3 thrombocytopenia with bleeding, grade 3 non-he matologic toxicity (except for nausea and alopecia), or > 2 week delay in c hemotherapy recycling. The above dose level was defined as maximum tolerate d 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. Stom atitis occurred in 11 patients across all dose levels, considering all deli vered 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 toxi city, occurring in 14 patients. Other side effects were mild. One complete response (4%) and seven partial responses (29%) were observed, for an overa ll response rate of 33% (95% confidence interval (95% CI): 16%-55%). Conclusions: Caelyx is a safe and promising new treatment in HNC, that dese rves further evaluation both alone and integrated within chemo-radiotherapy strategies.