title: Liposomal doxorubicin and conventionally fractionated radiotherapy in the treatment of locally advanced non-small-cell lung cancer and head and neck cancer.
abstract: OBJECTIVE
  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).
  
  
  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/m(2) every 2 weeks (for three cycles during radiotherapy) and was increased by 5 mg/m(2) 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 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Radiotherapy and Oncology, Nuclear Medicine, and Otolaryngology-Head and Neck Surgery, University Hospital of Iraklion, Crete, Greece. targ@her.forthnet.gr
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: S
authors.initials: S
authors.lastname: Koukouraki
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: S C
authors.initials: SC
authors.lastname: Archimandritis
authors.forename: J
authors.initials: J
authors.lastname: Skarlatos
authors.forename: K
authors.initials: K
authors.lastname: Beroukas
authors.forename: J G
authors.initials: JG
authors.lastname: Bizakis
authors.forename: G
authors.initials: G
authors.lastname: Retalis
authors.forename: N
authors.initials: N
authors.lastname: Karkavitsas
authors.forename: E S
authors.initials: ES
authors.lastname: Helidonis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004337:Drug Carriers; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D016014:Linear Models; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin