title: Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study.
abstract: BACKGROUND
  Taxane/platinum combinations exhibit synergistic cytotoxicity and activity against a broad range of solid tumours. We sought to optimise the regimen as a suitable outpatient palliative treatment for cancer of unknown primary (CUP).
  
  
  METHODS
  Eligible CUP patients with adenocarcinoma or poorly differentiated carcinoma, performance status of 0-2, adequate organ function and assessable disease were treated with docetaxel 75 mg/m(2) and carboplatin at an area under the concentration time-curve (AUC) of 5, both as 30-minute intravenous infusions, every three weeks. Patients with isolated axillary adenopathy, squamous cell cervical or inguinal adenopathy and PSA or germ-cell serum tumour markers were excluded.
  
  
  RESULTS
  Forty-seven patients entered the trial, 24 with predominantly nodal disease or non-mucinous peritoneal carcinomatosis (favourable risk) and 23 with visceral metastases (unfavourable risk). A median of 6 cycles of chemotherapy were administered, with relative dose intensities of both drugs >90%. Response rates were 32% (46% in favourable risk, 17% in unfavourable), comparable to the activity of paclitaxel/platinum regimes, though complete remissions were seen only in favourable risk patients. Granulocyte-colony stimulating factor support was used in a third of treatment cycles. Toxicity was mild and manageable, with grade 3-4 neutropenia in 26% of patients, febrile neutropenia in 7% and severe non-hematologic side-effects in less than 8% of patients. No toxic deaths or severe neurotoxicity were seen. Median time to progression (TTP) and overall survival (OS) were 5.5 and 16.2 months respectively. Survival was driven mainly by favourable-risk patients (22.6 months), as those with visceral metastases had a poor median survival of only 5.3 months. Good performance status and low-volume disease predicted for superior outcome, while docetaxel relative dose-intensity was a positive prognosticator only in favourable-risk patients.
  
  
  CONCLUSIONS
  One-hour docetaxel/carboplatin is a convenient, safe and effective outpatient palliative treatment for CUP patients, providing meaningful survival prolongation only in favourable-risk patients. Insights in the molecular biology of CUP are needed for the development of targeted therapeutic manipulations of malignant resistance and progression.
authors.affiliation: Ioannina University Hospital, Ioannina, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Evangelos
authors.initials: E
authors.lastname: Briasoulis
authors.forename: Haralambos P
authors.initials: HP
authors.lastname: Kalofonos
authors.forename: Georgios
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
authors.forename: George
authors.initials: G
authors.lastname: Samelis
authors.forename: Aris
authors.initials: A
authors.lastname: Koutras
authors.forename: Maria
authors.initials: M
authors.lastname: Karina
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Xiros
authors.forename: Epameinondas
authors.initials: E
authors.lastname: Samantas
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000553:Ambulatory Care / Q000379:methods; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006115:Greece; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000473:pathology; D010045:Outpatients; D010166:Palliative Care / Q000379:methods*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin