title: Phase I Dose-Escalation Study of Weekly Paclitaxel and Cisplatin Followed by Radical Hysterectomy in Stages IB2 and IIA2 Cervical Cancer.
abstract: OBJECTIVE
  To define the optimal dose of paclitaxel combining cisplatin, as weekly neoadjuvant chemotherapy (NAC) for early-stage bulky squamous cell carcinoma of the uterine cervix.
  
  
  METHODS
  A prospective trial was conducted for International Federation of Gynecology and Obstetrics stages IB2 and IIA2 cervical squamous cell carcinoma patients with magnetic resonance imaging or positron emission tomography-defined lymph node negative. Weekly fixed-dose cisplatin (40 mg/m) and 4-level dose escalation of paclitaxel (50, 60, 70, 80 mg/m) for 3 courses was given and followed by radical hysterectomy and pelvic lymph node dissection (RH-PLND) 14 to 28 days later. Postoperative adjuvant therapy was tailored according to pathologic response.
  
  
  RESULTS
  No dose-limiting toxicity occurred. Twelve subjects were enrolled without reaching maximum tolerated dose, nor was any RH-PLND procedure delayed for >2 weeks. Pathologic response rate was 50% (complete in 2 and partial in 4). Paclitaxel dose level seemed unrelated to pathologic response. No subjects had grade ≥3 acute adverse events. Seven patients (58.3%) received postoperative radiotherapy or chemoradiation. Patients with human papillomavirus 16-negative tumor and aged 55 years and older had marginally higher risk (100%) of adjuvant radiotherapy or chemoradiation after NAC than those with human papillomavirus 16-positive or age less than 55 (P=0.081). With a median follow-up of 45.5 months, all 12 patients remained alive without disease.
  
  
  CONCLUSIONS
  Weekly paclitaxel and cisplatin NAC for 3 courses can be tolerated with excellent short-term outcome. With the caveat of small number of patients, this study supports future phase II trials of weekly paclitaxel and cisplatin NAC for 4 to 5 cycles.
authors.affiliation: Departments of *Obstetrics and Gynecology ∥Pathology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine §Clinical Trial Center †Gynecologic Cancer Research Center, Chang Gung Memorial Hospital Departments of ¶Nuclear Medicine #Medical Imaging and Intervention, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan ‡Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hung-Hsueh
authors.initials: HH
authors.lastname: Chou
authors.forename: Huei-Jean
authors.initials: HJ
authors.lastname: Huang
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.forename: Lan-Yan
authors.initials: LY
authors.lastname: Yang
authors.forename: Swei
authors.initials: S
authors.lastname: Hsueh
authors.forename: Feng-Yuan
authors.initials: FY
authors.lastname: Liu
authors.forename: Yen-Lyin
authors.initials: YL
authors.lastname: Liou
authors.forename: Jui-Der
authors.initials: JD
authors.lastname: Liou
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Chen
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.forename: Gigin
authors.initials: G
authors.lastname: Lin
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Chang
authors.forename: Chyong-Huey
authors.initials: CH
authors.lastname: Lai
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy* / Q000821:virology; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D007044:Hysterectomy; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D010388:Pelvis; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy* / Q000821:virology
chemical_list: D017239:Paclitaxel; D002945:Cisplatin