title: Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer.
abstract: In a phase I study we demonstrated the feasibility of a bi-weekly combination of paclitaxel 180 mg x m(-2) with cisplatin 60 mg x m(-2). In this study we further assessed toxicity and efficacy of this schedule in the treatment of advanced cancer of the oesophagus or the gastro-oesophageal junction. Patients received paclitaxel 180 mg x m(-2) administered over 3 h followed by a 3-h infusion of cisplatin 60 mg x m(-2). Patients were retreated every 2 weeks unless granulocytes were <0.75x10(9) or platelets <75x10(9). Patients were evaluated after three and six cycles and responding patients received a maximum of eight cycles. Fifty-one patients were enrolled into the study. The median age was 56 years (range 32-78). WHO performance status were: 0 (19 patients); 1 (29 patients); 2 (three patients). All patients received at least three cycles of chemotherapy and all were evaluable for toxicity and response. Haematological toxicity consisted of uncomplicated neutropenia grade 3 in 39% and grade 4 in 31% of patients. Five patients (10%) were hospitalised, three patients because of treatment related complications and two patients because of infections without neutropenia. Sensory neurotoxicity was the predominant non-haematological toxicity; grade 1 and 2 neurotoxicity was observed in 43 and 20% of patients, respectively. Response evaluation in 51 patients with measurable disease: complete response 4%, partial response 39%, stable disease 43% and progressive disease in 14% of the patients. The median duration of response was 8 months. The median survival for all patients was 9 (range 2-29+) months and the one-year survival rate was 43%. Four patients who received additional local treatment (two patients surgery and two patients radiotherapy) are still disease free after a follow-up of 20-29 months. This bi-weekly treatment of paclitaxel and cisplatin is well tolerated by patients with advanced oesophageal cancer. The toxicity profile of this regimen compares favourable to that of previously used cisplatin- and paclitaxel-based regimens. Trials are underway evaluating this bi-weekly regimen in a neo-adjuvant setting.
authors.affiliation: Department of Medical Oncology, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
authors.forename: M B
authors.initials: MB
authors.lastname: Polee
authors.forename: F A L M
authors.initials: FA
authors.lastname: Eskens
authors.forename: M E L
authors.initials: ME
authors.lastname: van der Burg
authors.forename: T A W
authors.initials: TA
authors.lastname: Splinter
authors.forename: P D
authors.initials: PD
authors.lastname: Siersema
authors.forename: H W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: A
authors.initials: A
authors.lastname: van der Gaast
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000187:drug effects; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D017239:Paclitaxel; D002945:Cisplatin