title: Induction therapy for poor-prognosis anal canal carcinoma: a phase II study of the cancer and Leukemia Group B (CALGB 9281).
abstract: OBJECTIVE
  Although most patients with anal canal cancer are cured with sphincter-preserving, nonsurgical, combined-modality therapy, those with large tumors and lymph node involvement have a poor prognosis. To establish the safety and efficacy of induction chemotherapy with infusional fluorouracil (FU) plus cisplatin followed by FU plus mitomycin C with concurrent radiation in patients with poor-prognosis squamous cell cancers of the anal canal.
  
  
  METHODS
  Patients with previously untreated anal canal cancers with T3 or T4 tumors and/or extensive nodal involvement (bulky N2 or N3) received two 28-day cycles of induction treatment with infusional FU plus cisplatin followed by two 28-day cycles of FU plus mitomycin C with concurrent split-course radiation. A third cycle of FU and cisplatin with radiation boost was given to patients with persistent primary site disease or bulky N2 or N3 disease at presentation.
  
  
  RESULTS
  Forty-five assessable patients received protocol therapy. Treatment was generally well tolerated, and gastrointestinal and hematologic toxicities were the most common. Induction chemotherapy resulted in eight complete and 21 partial responses. After induction, combined-modality, and boost therapy, 37 (82%) of 45 assessable high-risk patients achieved a complete response. After 4 years of follow-up, 68% of patients are alive, 61% are disease-free, and 50% are colostomy- and disease-free.
  
  
  CONCLUSIONS
  A combined-modality approach that includes induction treatment with FU and cisplatin followed by combined-modality therapy with FU, mitomycin C, and concurrent radiation results in long-term disease control in the majority of patients with poor-prognosis anal canal cancer.
authors.affiliation: Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA. neal.meropol@fccc.edu
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: Brenda
authors.initials: B
authors.lastname: Shank
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Colacchio
authors.forename: John
authors.initials: J
authors.lastname: Ellerton
authors.forename: Frank
authors.initials: F
authors.lastname: Valone
authors.forename: Susan
authors.initials: S
authors.lastname: Budinger
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Day
authors.forename: Judy
authors.initials: J
authors.lastname: Hopkins
authors.forename: Joel
authors.initials: J
authors.lastname: Tepper
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016685:Mitomycin; D002945:Cisplatin; D005472:Fluorouracil