Cisplatin Plus One-Day 24-hour Infusion of High-Dose 5-Fluorouracil for Stage IVB, Recurrent or Metastatic Carcinoma of the Uterine Cervix
Condition: Cervical Cancer
MeSH terms: Uterine Cervical Neoplasms
Study type: Observational

Summary: 
      Objectives: To evaluate the effectiveness and toxicity of the combination of infusional
      cisplatin and 24-hour infusion of high-dose fluorouracil plus leucovorin (P-HDFL) repeatedly
      every 21 days for the treatment of stage IVB, recurrent or metastatic carcinoma of cervix.

      Methods: The medical records of all patients with stage IVB, recurrent or metastatic cervical
      cancer who were treated with P-HDFL regimen between January 2005 and December 2009 at
      National Taiwan University Hospital were reviewed.

      Expected results: Investigators will identify the effectiveness and toxicity of the
      combination of infusional cisplatin and 24-hour infusion of high-dose fluorouracil plus
      leucovorin (P-HDFL) repeatedly every 21days for the treatment of stage IVB, recurrent or
      metastatic carcinoma of cervix.
    

Detailed description: 
      The medical records for all patients with advanced, metastatic or recurrent cervical cancer
      who were treated with P-HDFL regimen between January 2005 and December 2009 at National
      Taiwan University Hospital were reviewed. Recurrences were confirmed by histopathologic
      examinations. Cases of recurrent cervical cancer, who undergoing salvage surgery and
      receiving P-HDFL as adjuvant therapy, were excluded from this study. The general principles
      for patients schedule for P-HDFL regimen treatment were as followings: patients must have had
      white cell count > 3000/mm3, platelet count > 100000/mm3, a normal serum creatinine (≦1.5
      mg/dL) or a measured creatinine clearance ([urine creatinine level (mg/dL) X 24-hr urine
      amount (mL)]/[serum creatinine level (mg/dL) X 1,440 min]) of ≧ 40 mL/min [12,15], total
      bilirubin ≦ 2 mg/dL, and transaminase (≦3X the upper normal limits). Also, patients needed to
      have measurable disease by radiographic studies (plain X-ray, CT or MRI scans), no serious
      active underlying medical issues, and Eastern Cooperative Oncology Group (ECOG) performance
      status of 0 to 2. The ethical approval for this retrospective study was obtained from our
      research ethics committee in this hospital.

      The P-HDFL regimen was given as follows: In each 21-day cycle, patients received 24-hour
      infusions of cisplatin at 45 or 50 mg/m2 and 5-FU 2,600mg/m2 plus leucovorin 300 mg/m2
      intravenous 24-hour infusion on Day 1. Normal saline hydration (≧1000 mL), dexamethasone, and
      antiemetics (ondansetron or granisetron) were given prophylactically before each dose of
      cisplatin.

      Physical examination, survey of adverse reactions and hemogram checkup of patients were
      performed before administering each dose of the P-HDFL treatment. Tumor response and toxicity
      were evaluated according to the World Health Organization criteria [16]. A complete response
      (CR) was defined as the disappearance of all measurable disease for at least 4 weeks. A
      partial response (PR) was defined as a 50% or more reduction in the products of each
      measurable lesion for at least 4 weeks. Progressive disease (PD) was defined as a 25% or more
      increase in the size of one or more measurable lesions or the appearance of new lesions.
      Stable disease (SD) was defined as any condition not meeting any the above criteria.

      Progression-free survival was measured from the first date of chemotherapy to the date of
      documented disease progression, death of other causes or last contact. Overall survival was
      measured from the first date of chemotherapy to death or last contact. Progression-free
      survival and overall survival were estimated by using the method of Kaplan-Meier.
    

Intervention name(s): Cisplatin,P-HDFL
Intervention type(s): Drug
Intervention description(s): The P-HDFL regimen was given as follows: In each 21-day cycle, patients received 24-hour infusions of cisplatin at 45 or 50 mg/m2 and 5-FU 2,600mg/m2 plus leucovorin 300 mg/m2 intravenous 24-hour infusion on Day 1. Normal saline hydration (≧1000 mL), dexamethasone, and antiemetics (ondansetron or granisetron) were given prophylactically before each dose of cisplatin.
Other intervention name(s): Abilatin、Platamine、Platinex; fluorouracil
Intervention MeSH terms: Fluorouracil
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        The general principles for patients schedule for P-HDFL regimen treatment were as
        followings: patients must have had white cell count > 3000/mm3, platelet count >
        100000/mm3, a normal serum creatinine (≦1.5 mg/dL) or a measured creatinine clearance
        ([urine creatinine level (mg/dL) X 24-hr urine amount (mL)]/[sereum creatinine level
        (mg/dL) X 1,440 min]) of ≧ 40 mL/min [12,15], total bilirubin ≦ 2 mg/dL, and transaminase
        (≦3X the upper normal limits). Also, patients needed to have measurable disease by
        radiographic studies (plain X-ray, CT or MRI scans), no serious active underlying medical
        issues, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
      
Keywords: cisplatin; Cervical cancer; metastasis; recurrence