title: A phase I study of concurrent weekly carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy as an adjuvant treatment for early-stage cervical cancer patients with positive pelvic lymph nodes.
abstract: OBJECTIVE
  The objective of this study was to determine the maximum tolerated dose (MTD) and acute dose-limiting toxicities (DLTs) of intravenous carboplatin plus paclitaxel combined with intensity-modulated pelvic radiotherapy (pelvic IMRT) as an adjuvant treatment for early-stage cervical cancer patients with positive pelvic lymph nodes.
  
  
  METHODS
  Women with uterine cervical cancer who were treated with radical hysterectomy and pelvic lymphadenectomy and displayed positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic IMRT (50.4 Gy). The concurrent weekly chemotherapy consisted of carboplatin (area under the curve [AUC], 2) and paclitaxel (starting at 35 mg/m² and escalating by 5 mg/m² in 3 patient cohorts). The primary end point of the escalation study was acute DLT that occurred within 30 days of the completion of radiation therapy.
  
  
  RESULTS
  Nine patients were enrolled and treated at 2 dose levels until DLT occurred. The median age of the patients was 47 years (range, 28-66 years). The median radiotherapy treatment time was 39.5 days (range, 38-64 days). At dose level I (35 mg/m² paclitaxel), 2 grade 3 leukopenia and a neutropenia were observed, but no DLT occurred. At dose level II (40 mg/m² paclitaxel), the first patient experienced a grade 2 hypersensitive reaction, which resulted in discontinuation of planned treatment. Thus, 2 more patients were evaluated at this dose level. Of these, 1 patient experienced febrile neutropenia, which was considered to be a DLT, and the other patient experienced long-lasting grade 3 leukopenia and grade 3 neutropenia, which resulted in the discontinuation of chemotherapy for 2 weeks (a DLT). We then evaluated 3 more patients at dose level 1, but no DLT occurred. The MTD of paclitaxel and carboplatin was thus defined as 35 mg/m² and an AUC of 2.0, respectively.
  
  
  CONCLUSIONS
  Weekly paclitaxel/carboplatin and pelvic IMRT is a reasonable adjuvant treatment regimen for cervical cancer patients after radical hysterectomy. The MTD of paclitaxel and carboplatin for future phase II trials of this regimen is 35 mg/m² and an AUC of 2.0, respectively.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan. smabuchi@gyne.med.osaka-u.ac.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Mabuchi
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takahashi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Isohashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoi
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Ito
authors.forename: Tateki
authors.initials: T
authors.lastname: Tsutui
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ogata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D010386:Pelvic Neoplasms / Q000556:secondary / Q000628:therapy*; D011379:Prognosis; D050397:Radiotherapy, Intensity-Modulated; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D016190:Carboplatin; D017239:Paclitaxel