title: Prolonged chemoradiation in locally advanced carcinoma of the uterine cervix: final results of a phase II study (ESTER-1).
abstract: BACKGROUND
  The aim of this phase II study was to evaluate response and toxicity of a prolonged chemoradiation regimen in patients with locally advanced cervical cancer.
  
  
  METHODS
  Three cycles of concomitant chemotherapy were used with cisplatin (20 mg/m², 2-hour intravenous infusion, days 1-4) and 5-fluorouracil (1000 mg/m², 24-hour continuous intravenous infusion, days 1-4) administered at weeks 1, 5, and 9 of radiotherapy. In combination, radiotherapy was delivered to a planning target volume (PTV) defined as the CTV (clinical target volume) plus 8 mm. The CTV was defined as follows: gross tumor volume, upper half of the vagina (if not involved) or the whole vagina (if clinically involved), uterus, obturator nodes, external iliac nodes, internal iliac nodes, and the presacral nodes (cranial to S2). The prescribed dose to the PTV was 50 Gy, 2 Gy/fraction (ICRU 62) delivered in 25 fractions with a 2-week break at 20Gy and 40 Gy (split-course technique). Early and late toxicity was assessed according to the RTOG and RTOG/EORTC toxicity scales. Perioperative toxicity was evaluated according to the Chassagne classification of surgical complications.
  
  
  RESULTS
  A total of 25 patients were included in this study. Median age was 52 years (range, 28-69). Clinical stage was: IB2-II: 19 patients (76%), III-IVA: 6 patients (24%). All patients completed the prescribed dose of chemoradiation and were evaluated 4 weeks after the end of treatment. Complete and partial clinical local response was observed in 4 and 19 patients, respectively (totaling 92% of clinical responses). About 32% of patients experienced grade 3 to 4 toxicity, in particular, grade 3 or 4 hematological toxicity was observed in 7 patients and 1 patient developed grade 3 genitourinary toxicity. No patients developed grade 3 gastrointestinal toxicity or skin toxicity. Of total, 22 patients (88%) underwent radical hysterectomy. Seven patients (28%) showed a complete response (CR) to treatment, and 7 patients (28%) showed microscopic residual disease (μPR), totaling 14 patients (56%) complete/partial microscopic responses. Perioperative morbidity was higher than reported in historical controls especially in terms of tissue fibrosis (64%) and perioperative urinary toxicity (14%). Actuarial 2-year local control, disease-free survival, and overall survival were 65.5%, 61.8%, and 80.8%, respectively.
  
  
  CONCLUSIONS
  A prolonged treatment with more chemotherapy courses does not improve tumor response and increases the risk of perioperative complication. This treatment regimen, considering the low incidence of acute gastrointestinal toxicity, might be tested in the adjuvant setting.
authors.affiliation: "John Paul II" Center for High Technology Research and Education in Biomedical Sciences, Catholic University, 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: Legge
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.forename: Valeria
authors.initials: V
authors.lastname: Ruggieri
authors.forename: Domenica
authors.initials: D
authors.lastname: Lorusso
authors.forename: Gilbert D A
authors.initials: GD
authors.lastname: Padula
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 / Q000008:administration & dosage* / Q000009:adverse effects; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007044:Hysterectomy / Q000379:methods; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011300:Preoperative Care; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*