Liposomal Doxorubicin and Conventionally Fractionated Radiotherapy in the Treatment of Locally Advanced Non–Small-Cell Lung Cancer and Head and Neck Cancer

PURPOSE: Stealth (ALZA Corporation, Palo Alto, CA) liposomal drug formulation allows a higher intratumoral accumulation and a prolonged plasma half-life of the encapsulated drugs. In the study presented here, we evaluated the feasibility of Stealth liposomal doxorubicin (Caelyx; ALZA Corporation) administered concurrently with conventionally fractionated radiotherapy in the treatment of non–small-cell lung cancer (NSCLC) and head and neck cancer (HNC). PATIENTS AND METHODS: Fifteen patients with NSCLC and 15 with squamous-cell HNC were recruited in two phase I dose-escalation trials. The starting dose of Caelyx was 10 mg/m2 every 2 weeks (for three cycles during radiotherapy) and was increased by 5 mg/m2 dose increments for every three patients. RESULTS: The maximum tolerated dose of Caelyx was 20 mg/m2 for HNC and 25 mg/m2 in NSCLC patients. Oral/pharyngeal mucositis was the dose-limiting toxicity for HNC patients. “In field” radiation skin toxicity was slightly increased. Hematologic toxicity was minimal. Single photon emission computed tomographic evaluation of Caelyx distribution, using technetium-99m–diethylenetriamine pentaacetic acid labeling, revealed a high intratumoral accumulation of the drug. The tumor to thoracic vessel area count ratio in the NSCLC cases ranged from 0.6 to 1.6 (mean ± SD, 1.01 ± 0.29), whereas this ratio was higher (0.8 to 1.85; mean ± SD, 1.35 ± 0.39) in HNC cases (P = .049). The complete response rate was 21% in the NSCLC cases and 75% in the HNC cases. NSCLC cases with higher Caelyx tumor accumulation responded better to the regimen. The tumor microvessel density assessed with the anti-CD31 monoclonal antibody directly correlated with the degree of the Caelyx accumulation (P = .007; r = .92). CONCLUSION: We conclude that combination of radiotherapy with Stealth liposomal doxorubicin is feasible. The potential role of such a regimen in the treatment of highly angiogenic tumors requires further investigation.