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, Polo Alto, CA) liposomal drug formulati on allows a higher intratumoral accumulation and a prolonged plasma half-li fe of the encapsulated drugs, In the study presented here, we evaluated the feasibility of Stealth liposomal doxorubicin (Caelyx; ALZA Corporation) ad ministered concurrently with conventionally fractionated radiotherapy in th e 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 dos e of Caelyx was 10 mg/m(2) every 2 weeks (for three cycles during radiother apy) and was increased by 5 mg/m2 dose increments for every three patients, Results: The maximum tolerated dose of Caelyx was 20 mg/m(2) for HNC and 25 mg/m(2) in NSCLC patients, Oral/pharyngeal mucositis was the dose-limiting toxicity for HNC patients. "In field" radiation skin toxicity wets slightl y increased, Hematologic toxicity was minimal. Single photon emission compu ted tomographic evaluation of Caelyx distribution, using technetium-99m-die thylenetriamine pentaacetic acid labeling, revealed a high intratumoral acc umulation 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 t his 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% i n the HNC cases, NSCLC cases with higher Caelyx tumor accumulation responde d better to the regimen. The tumor microvessel density assessed with the an ti-CD31 monoclonal antibody directly correlated with the degree of the Cael yx accumulation (P =.007; r=.92), Conclusion: We conclude that combination of radiotherapy with Stealth lipos omal doxorubicin is feasible. The potential role of such a regimen in the t reatment of highly angiogenic tumors requires further investigation. (C) 19 99 by American Society of Clinical Oncology.