title: Concomitant boost dose escalation plus large-field preoperative chemoradiation in locally advanced carcinoma of the uterine cervix: results of a phase I study (LARA-CC-1).
abstract: OBJECTIVE
  To determine the recommended preoperative dose of large-field chemoradiation along with concomitant boost dose escalation on the tumor in locally advanced cervical carcinoma (LACC).
  
  
  METHODS
  A radiation dose of 40Gy over four weeks, 2Gy per fraction, was delivered to the tumor and the lymphatic drainage (planning target volume, PTV2), which encompassed a volume larger than standard (upper field border: L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the macroscopic tumor only (PTV1) with a concomitant boost strategy. Three dose levels were planned: levels 1 (no PTV1 boost), 2 (45/2.25Gy) and 3 (50/2.5Gy). Patients were treated in cohorts of six to twelve per group using a standard phase I study design. The recommended dose was exceeded if >2 of 6 patients in a cohort experienced dose-limiting toxicity (DLT).
  
  
  RESULTS
  32 patients (median age: 50 years; FIGO stage IB2: 4, IIA: 3, IIB: 21, III-IVA: 4) were enrolled. Median follow-up was 18 months (3-49 months). The most common grade 3/4 toxicity was gastrointestinal (diarrhea). Since three DLTs (grade 3 diarrhea, n=2; grade 3 proctitis, n=1), were observed in 4 patients at level 3, the trial was closed and level 2 was judged as the recommended dose.
  
  
  CONCLUSIONS
  Based on the data from this phase I study, 45Gy/2.25Gy to macroscopic tumor and 40Gy/2Gy to lymphatic drainage may be considered the recommended doses.
authors.affiliation: Radiotherapy Unit, Department of Oncology, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Largo A. Gemelli 1, Campobasso, Italy. gmacchia@rm.unicatt.it
authors.forename: Gabriella
authors.initials: G
authors.lastname: Macchia
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.forename: Valeria
authors.initials: V
authors.lastname: Ruggieri
authors.forename: Mariangela
authors.initials: M
authors.lastname: Massaccesi
authors.forename: Vanda
authors.initials: V
authors.lastname: Salutari
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.forename: Numa
authors.initials: N
authors.lastname: Cellini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007044:Hysterectomy; D008197:Lymph Node Excision; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D011879:Radiotherapy Dosage; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D002945:Cisplatin; D005472:Fluorouracil