title: Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix carcinoma.
abstract: OBJECTIVE
  Although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer.
  
  
  METHODS
  24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m2/week was increased in 5-mg/m2 increments to two levels. The standard dose of CDDP was 20-25 mg/m2/week.
  
  
  RESULTS
  Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m2/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6).
  
  
  CONCLUSIONS
  
  
  
  CONCLUSIONS
  The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m2/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising.
authors.affiliation: Department of Radiotherapy and Oncology, Medical School of Crete University, Iraclion University Hospital, Greece. varveris@med.uoc.gr
authors.forename: Haralambos
authors.initials: H
authors.lastname: Varveris
authors.forename: Stefanos
authors.initials: S
authors.lastname: Kachris
authors.forename: Michael
authors.initials: M
authors.lastname: Mazonakis
authors.forename: Efrossini
authors.initials: E
authors.lastname: Lyraraki
authors.forename: Effie
authors.initials: E
authors.lastname: Petineli
authors.forename: Antonios
authors.initials: A
authors.lastname: Varveris
authors.forename: Anastasia
authors.initials: A
authors.lastname: Fasoulaki
authors.forename: Antonios
authors.initials: A
authors.lastname: Tzedakis
authors.forename: Vasilis
authors.initials: V
authors.lastname: Kouloulias
authors.forename: Angeliki
authors.initials: A
authors.lastname: Zolindaki
authors.forename: Maria
authors.initials: M
authors.lastname: Vlachaki
mesh_terms: D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000627:therapeutic use* / Q000633:toxicity; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D004317:Doxorubicin; D002945:Cisplatin