title: A prospective randomized phase II study comparing metronomic chemotherapy with chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or inoperable squamous cell carcinoma of head and neck.
abstract: BACKGROUND
  Cetuximab based treatment is the recommended chemotherapy for head and neck squamous cell cancers in the palliative setting. However, due to financial constraints, intravenous (IV) chemotherapy without cetuximab is commonly used in lesser developed countries. We believe that oral metronomic chemotherapy may be safer and more effective in this setting.
  
  
  METHODS
  We conducted an open label, superiority, parallel design, randomized phase II trial comparing oral MCT [daily celecoxib (200mg twice daily) and weekly methotrexate (15mg/m(2))] to intravenous single agent cisplatin (IP) (75mg/m(2)) given 3 weekly. Eligible patients had head and neck cancers requiring palliative chemotherapy with ECOG PS 0-2 and adequate organ functions who could not afford cetuximab. The primary end point was progression-free survival.
  
  
  RESULTS
  110 Patients were recruited between July 2011 to May 2013, 57 randomized to the MCT arm and 53 to the IP arm. Patients in the MCT arm had significantly longer PFS (median 101 days, 95% CI: 58.2-143.7 days) compared to the IP arm (median 66 days, 95% CI; 55.8-76.1 days) (p=0.014). The overall survival (OS) was also increased significantly in the MCT arm (median 249 days, 95% CI: 222.5-275.5 days) compared to the IP arm (median 152 days, 95% CI: 104.2-199.8 days) (p=0.02). There were fewer grade 3/4 adverse effects with MCT, which was not significant. (18.9% vs. 31.4%, P=0.14).
  
  
  CONCLUSIONS
  Oral metronomic chemotherapy has significantly better PFS and OS than single agent platinum in the palliative setting.
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, India.
authors.forename: Vijay Maruti
authors.initials: VM
authors.lastname: Patil
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, India.
authors.forename: Vanita
authors.initials: V
authors.lastname: Noronha
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, India.
authors.forename: Vamshi Krishna
authors.initials: VK
authors.lastname: Muddu
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, India.
authors.forename: Sachin
authors.initials: S
authors.lastname: Dhumal
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, India.
authors.forename: Bharatsingh
authors.initials: B
authors.lastname: Bhosale
authors.affiliation: Department of Radio Diagnosis, Tata Memorial Centre, Mumbai, India.
authors.forename: Supreeta
authors.initials: S
authors.lastname: Arya
authors.affiliation: Department of Radio Diagnosis, Tata Memorial Centre, Mumbai, India.
authors.forename: Shashikant
authors.initials: S
authors.lastname: Juvekar
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, India.
authors.forename: Shripad
authors.initials: S
authors.lastname: Banavali
authors.affiliation: Department of Head and Neck Surgery, Tata Memorial Centre, Mumbai, India.
authors.forename: Anil
authors.initials: A
authors.lastname: D'Cruz
authors.affiliation: Division of Clinical Research and Biostatistics, Malabar Cancer Centre, India.
authors.forename: Atanu
authors.initials: A
authors.lastname: Bhattacharjee
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, India. Electronic address: kumarprabhashtmh@gmail.com.
authors.forename: Kumar
authors.initials: K
authors.lastname: Prabhash
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000068579:Celecoxib; D002945:Cisplatin / Q000008:administration & dosage; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D011720:Pyrazoles / Q000008:administration & dosage; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D002945:Cisplatin; D008727:Methotrexate
keywords: Chemotherapy; Cisplatin; Head and neck cancer; Metronomic administration; Oral cancer; Palliative