title: Pegulated liposomal doxorubicin and cisplatin given concurrently with conventional radiotherapy: a phase I dose-escalation trial for patients with squamous cell carcinoma of head and neck and lung.
abstract: This is a phase I study of concurrent chemoradiation with pegulated liposomal doxorubicin (PLDH) and cisplatin for patients with squamous non-small cell lung cancer (NSCLC) and head and neck carcinoma (SCCHN). Nine patients with NSCLC and 9 with SCCHN were recruited in two phase I dose-escalation trials. The starting dose of PLDH was 7 mg/m2 once a week and was increased by 5 mg/m2 dose increments for every 3 patients. The standard dose of cisplatin was 20 mg/m2 once a week for 6.5-7 weeks of conventional external irradiation. The total tumor dose was 64 and 70 Gy for NSCLC and SCCHN patients respectively. The maximum tolerated dose of PLDH was 12 mg/m2 for the two cohorts of patients. Grade 3 mucositis was the dose limiting toxicity for NSCLC and SCCHN patients, at the 17 mg/m2 dose level. Three chemoradiation delays of 7 days were confirmed. The median time of follow-up was 17.9 months (range 3-36 months). Four patients died due to local-regional failure combined with distant metastases (3 patients) and pericardial effusion (1 patient). In total, there were 6/18 (33%) CRs (95% confidence interval, 11-55%), and 10/18 (55%), PRs (95% confidence interval, 32-78%). The recommended phase II PLDH dose combined to cisplatin and external irradiation is 12 mg/m2/week. The incorporation of PLDH in concomitant chemoradiation regimens for future treatment of squamous cell carcinoma of the lung and head and neck is warranted.
authors.affiliation: Department of Radiotherapy and Oncology, Heraklion University Hospital, Heraklion 71110, Crete, Greece. varveris@med.uoc.gr
authors.forename: H
authors.initials: H
authors.lastname: Varveris
authors.forename: S
authors.initials: S
authors.lastname: Kachris
authors.forename: M
authors.initials: M
authors.lastname: Mazonakis
authors.forename: E
authors.initials: E
authors.lastname: Lyraraki
authors.forename: A
authors.initials: A
authors.lastname: Markouizou
authors.forename: S
authors.initials: S
authors.lastname: Karabekios
authors.forename: A
authors.initials: A
authors.lastname: Tzedakis
authors.forename: K
authors.initials: K
authors.lastname: Perisinakis
authors.forename: J
authors.initials: J
authors.lastname: Damilakis
authors.forename: M
authors.initials: M
authors.lastname: Vlachaki
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry*; D011878:Radiotherapy / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002945:Cisplatin