title: Platinum-Fluoropyrimidine and Paclitaxel-Based Chemotherapy in the Treatment of Advanced Anal Cancer Patients.
abstract: Although treatment of localized anal cancer (AC) is well established, very little evidence is available to inform the management of advanced tumors, and the prognosis of these patients remains poor. We have analyzed treatment pathways and outcomes of a single-institution series of advanced AC patients in order to provide insight into the management of this rare condition.
  
  
  
  Inclusion criteria included epidermoid histology, inoperable locally recurrent or metastatic disease, and availability of full medical records. The primary objective was overall survival (OS). Prognostic factors were analyzed in univariate models.
  
  
  
  Sixty-four patients (1997-2014) were included: 16 (25.0%) with inoperable locally advanced and 48 (75.0%) with metastatic tumors. Fifty-one (79.7%) received at least one line of chemotherapy; of these, 37% underwent multimodality treatment. A combination of a platinum agent plus a fluoropyrimidine was the most common first-line regimen (74.5%), with an objective response rate (ORR) of 34.4% (95% confidence interval [CI], 18.6%-53.2%). Paclitaxel-based chemotherapy was used in 15 patients as front-line or salvage treatment, and the overall ORR was 53.3% (95% CI, 26.6%-78.7%). Median progression-free survival (PFS) after first- and second-line chemotherapy was 5.8 (interquartile range [IQR], 2.8-7.6) and 3.2 (IQR, 2.5-7.1) months, respectively. Five-year OS in the overall population was 15% (95% CI, 7.0%-25.0%). Age ≤65 years and liver metastases were predictive of better PFS (hazard ratio [HR], 0.39; 95% CI, 0.16-0.97;p= .04) and worse OS (HR, 2.25; 95% CI, 1.25-4.03;p= .01), respectively.
  
  
  
  A platinum agent plus a fluoropyrimidine and paclitaxel-based chemotherapy are active regimens for advanced AC. Clinical trials are needed to standardize treatment pathways, investigate the potential of novel therapeutics, and improve the poor prognosis of this rare condition.The Oncologist2017;22:402-408Implications for Practice:Because of the lack of randomized trials, the optimal management of advanced anal cancer is uncertain. Despite its retrospective analysis and relatively small sample size, this is the second largest study ever conducted in this setting, and, as such, it has the potential to serve as a valuable source of information for everyday clinical practice. These findings suggest that chemotherapy with a platinum agent plus a fluoropyrimidine or paclitaxel-containing regimens are reasonable treatment options for patients with inoperable locally recurrent or metastatic anal carcinoma.
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sclafani
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: Federica
authors.initials: F
authors.lastname: Morano
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: Chiara
authors.initials: C
authors.lastname: Baratelli
authors.affiliation: Department of Clinical Research & Development, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Kalaitzaki
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Watkins
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: Naureen
authors.initials: N
authors.lastname: Starling
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Chau
authors.affiliation: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom sheela.rao@rmh.nhs.uk.
authors.forename: Sheela
authors.initials: S
authors.lastname: Rao
mesh_terms: D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage*; D010984:Platinum / Q000008:administration & dosage*; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage*
chemical_list: D011743:Pyrimidines; D010984:Platinum; C030986:pyrimidine; D017239:Paclitaxel
keywords: Advanced anal cancer; Chemotherapy; InterAACT; Squamous cell carcinoma