4 Versus 6 Courses of Adjuvant Chemotherapy in LACC Patients Previously Treated With NACT Plus Radical Surgery
Condition: Uterine Cervical Neoplasms
MeSH terms: Uterine Cervical Neoplasms
Study type: Interventional

Summary: 
      The investigators primary outcome was to evaluate the effectiveness in term of Overall
      Survival (OS) and disease free interval (DFI) of two different platinum-based chemotherapic
      regimen (3 and 6 cycles) for treatment of Locally Advanced Cervical Cancer (LACC) (IB2-IIB)
      previously treated with Neoadjuvant Chemotherapy Plus Radical Surgery (NACT+RS).

      The secondary outcome was to evaluate and compare safety, in term of toxicity profile, of the
      two treatment options.
    

Detailed description: 
      Between February 2007 to January 2013, all patients with diagnosis of LAAC referred to the
      Division of Gynecologic Oncology of the Campus Bio-Medico University of Rome, were eligible
      for this protocol. The institutional internal review board approved the study. Inclusion
      criteria were: I) Patients with squamous cell, adenosquamous or adenocarcinoma of the cervix;
      II) Stage IB2-IIB according to the International Federation of Gynecology and Obstetrics
      (FIGO); III) age between 18 and 75 years; IV) Eastern Cooperative Oncology Group (ECOG)
      performance status 0-2; V) normal cardiac and respiratory functions; VI) absence of secondary
      malignancies; VII) no previous surgical, chemotherapic and/or radiotherapic treatment for
      secondary malignancies VIII) informed consent obtained from the patient.Exclusion criteria
      included: I) histological confirmation of papillary serous, mucinous, clear cell, squamous
      cell, mixed and undifferentiated carcinoma of the uterus; II) abnormal hepatic function
      (transaminases > 2.5 x upper limit, serum bilirubin > 1,5 x upper limit); III) abnormal renal
      function (creatinine clearance <60 mL/min and/or serum creatinine>2.0 mg/100 mL) function;
      IV) abnormal bone marrow function (absolute neutrophil count <1,5 x 109/L or platelet count <
      100 x 109/L or hemoglobin < 9 g/dL; V) severe or uncontrolled infection, other systemic
      diseases or mental illness; and VI) pregnant women. Clinical staging was performed according
      to the NCCN criteria, and included pelvic examination, cervical biopsy, abdomen-pelvis
      Computed Tomography, chest X-ray; examination under anesthesia, cystoscopy and/or proctoscopy
      if clinically indicated (National Comprehensive Cancer Network, Clinical Practicw Guidelines
      in Oncology. Cervical Cancer, Version 2.2015) All patients who met inclusion and exclusion
      criteria were enrolled and received 3 cycles of neoadjuvant chemotherapy (NACT) every three
      weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.

      Complete response was defined as complete disappearance of all clinically detect able
      disease, determined by 2 observations not less than 4 weeks apart. Partial response was
      recorded as ≥50% reduction in total tumor size, determined by 2 observations not less than 4
      weeks apart. No response or stable disease was defined as <50% decrease in tumor size or <25%
      increase in the size of one or more measurable lesions. Progressive disease was defined >25%
      increase in size or the appearance of new lesions.

      After NACT all patients with stable or progressive disease were excluded from the protocol,
      all others were underwent to bilateral systematic pelvic lymph node dissection, classical
      radical hysterectomy and bilateral salpingo-oophorectomy. Aortic lymphadenectomy, up to the
      level of the inferior mesenteric artery, was reserved to patients with pelvic node disease at
      intraoperative examination or finding of bulky aortic nodes at the time of surgery. In case
      of positive aortic nodes, hysterectomy was not performed, patients were excluded from the
      protocol and referred to radiation oncologists. Similarly patients who presented positive
      surgical margins or close vaginal margins (<0.5 mm) at final pathology, were excluded from
      the study and referred to radiotherapist. After surgery were randomly allocated to undergo 4
      or 6 cycles of chemotherapy by using a predetermined computer-generated randomisation code.
      In Group A, all patients received 4 cycles of adjuvant chemotherapy every three weeks
      according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.In Group B, all patients
      received instead 6 cycles of adjuvant chemotherapy every three weeks according to the same
      chemotherapic regimen. Adjuvant chemotherapy started within 28 days after surgery. Follow-up
      procedures included physical examination and vaginal cytology every 3 months for 2 years,
      then every 6 months until the 5th year according the NCCN 2015 and total body CT.

      Therefore in all patients in whom there was suspicion of relapse, the total body CT was
      anticipated.

      To assess the sample size, in agreement with the investigators experience, the investigators
      estimated a 20% reduction of the toxicity profile for patients who received 4 cycles of
      adjuvant chemotherapy compared to those who received 6 cycles (11; 19). Considering a power
      of 80%, to detect a statistically significant difference (alpha = 0.5; P = 0.05 Long Rank
      Test), 100 patients were necessary for each treatment arm.

      OS and DFS curves were estimated using the Kaplan-Meier method and differences were compared
      by use of the log-rank test.

      The comparison of other variables between two groups was evaluated using the Mann-Whitney
      test, the chi-square test, Fisher test. Statistical significance was set at p <0.05.

      DFS, OS and recurrence rate were analyzed only in those patients who completed the study
      protocol; toxicity profile of the two treatment groups, however, were statistically analyzed
      considering all patients randomized and enrolled in the study protocol after treatment with
      NACT + RS.
    

Intervention name(s): Group A adjuvant chemotherapy; Group B adjuvant chemotherapy; Cisplatin; Paclitaxel
Intervention type(s): Procedure; Procedure; Drug; Drug
Intervention description(s): In Group A, all patients received 4 cycles of adjuvant chemotherapy every three weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.; In Group B, all patients received 6 cycles of adjuvant chemotherapy every three weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.
Other intervention name(s): 4 cycles
Intervention MeSH terms: Paclitaxel; Cisplatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adjuvant chemotherapy