Biweekly Schedule of Docetaxel and Cisplatin in High Risk Patients With Unresectable Non-small Cell Lung Cancer (NSCLC)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Docetaxel and Cisplatin
Intervention description: splitted administration of docetaxel and cisplatin.
Intervention MeSH terms: Cisplatin; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: biweekly; docetaxel; cisplatin; non-small cell lung cancer

Summary:

      The rationale of phase II study of biweekly docetaxel and cisplatin in patients with
      unresectable NSCLC are follows:

      First, the optimal dose and schedule of combination with docetaxel and cisplatin are still
      controversial (3 weekly versus weekly).

      Platinum-based combination chemotherapy improves the survival of patients with advanced
      non-small cell lung cancer (NSCLC) in the first-line setting.

      Combination chemotherapy with docetaxel and cisplatin is one of the standard platinum-based
      regimens for treating NSCLC. However, usual standard 3 weekly regimen with docetaxel and
      cisplatin have consistently produced frequent Grade 3-4 neutropenia, and febrile neutropenia.

      Although weekly docetaxel and cisplatin is better tolerated than chemotherapy every 3 weeks,
      especially in the first line setting in terms of myelosuppression, the optimal dose and
      schedule for administration of the two drugs has not yet been determined.

      Both 3-weekly docetaxel plus cisplatin and weekly schedule showed similar response rates but
      had different toxicity profiles. The most frequent grade 3 or 4 toxicities were neutropenia
      in the 3 weekly schedule and fatigue or asthenia in the weekly schedule.

      Second, docetaxel and cisplatin have different action and mechanism. Docetaxel showed
      characteristic early bone marrow suppression 5-7 days after infusion compared with usual 14
      days after infusion of cisplatin. Thus, nadir period is not overlapped when the investigators
      administered both drugs concomittantly.

      Third, there are many feasible reports of biweekly administration of docetaxel in patients
      with NSCLC, breast cancer, stomach cancer, and ovarian cancer with better safety profiles.

      Therefore,the investigators designed this phase II study to evaluate the efficacy and
      toxicity of biweekly schedule of docetaxel and cisplatin in patients with unresectable NSCLC
      and test the hypothesis that biweekly schedule of docetaxel and cisplatin is better tolerated
      than both standard 3 week and weekly schedule in terms of hematologic (neutropenia) and
      non-hematologic toxicities (asthenia, interstitial pneumonitis. Additionally the
      investigators will evaluate polymorphism associated with this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  patients who were≥ 65 years of age and they had an Easten Cooperative Oncology Group
             (ECOG) performance status (PS) of 0-2, or the patients who were < 65 years of age and
             they had an ECOG PS 2

          -  histologically confirmed non-small cell carcinoma

          -  stages IIIB-IV disease

          -  adequate hematologic parameters (hemoglobin concentration of at least 9.0 g/dL,
             absolute neutrophil count ≥1,500/mm3, and platelet count ≥100,000/mm3), renal function
             (serum creatinine ≤1.5 mg/dL), and liver function (total bilirubin ≤1.5 mg/dL and
             serum transaminase level less than twice the upper limit of normal)

          -  at least one bi-dimensionally measurable lesion, according to the Response Evaluation
             Criteria In Solid Tumors (RECIST) version 1.1

        Exclusion Criteria:

          -  Active infection

          -  Prior chemotherapy, radiotherapy or surgery for their disease,

          -  A history of myocardial infarction in the last 3 months before entry to the study

          -  Uncontrolled congestive heart failure or hypertension

          -  Uncontrolled diabetes mellitus, pregnancy, lactation or a prior second primary cancer
             except for cervix cancer in situ or skin cancer

          -  All the patients provided written informed consent before they entered the study