title: Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma.
abstract: BACKGROUND
  To evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer.
  
  
  METHODS
  TNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response.
  
  
  RESULTS
  29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%).
  
  
  CONCLUSIONS
  Concurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to determining the role of intensity-modulated radiotherapy.
authors.affiliation: Medical Care Unit, Department of Medicine, European Institute of Oncology, via Ripamonti 435, Milan 20141, Italy. maria.zampino@ieo.it
authors.forename: Maria G
authors.initials: MG
authors.lastname: Zampino
authors.forename: Elena
authors.initials: E
authors.lastname: Magni
authors.forename: Maria C
authors.initials: MC
authors.lastname: Leonardi
authors.forename: Luigi
authors.initials: L
authors.lastname: Santoro
authors.forename: Elena
authors.initials: E
authors.lastname: Petazzi
authors.forename: Cristiana
authors.initials: C
authors.lastname: Fodor
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Petralia
authors.forename: Cristina
authors.initials: C
authors.lastname: Trovato
authors.forename: Franco
authors.initials: F
authors.lastname: Nolè
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D050397:Radiotherapy, Intensity-Modulated; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D002945:Cisplatin; D005472:Fluorouracil