Phase I/II Trial of Infusional Gemcitabine in Combination With Carboplatin in Chemonaive Non-small Cell Carcinoma

Inclusion Criteria:

• • Histologically or cytologically confirmed NSCLC.

  • Stage IIIB unsuitable for radical radiation (eg. with cytologically proven malignant effusion) or stage IV disease as defined by the AJCC criteria (see appendix 1).
  • Karnofsky performance status 70% or higher (see appendix 2).
  • Presence of at least one bidimensionally or unidimensionally measurable, non-CNS, indicator lesion defined by radiologic study or physical examination.
  • No previous chemotherapy for advanced disease. Prior neoadjuvant or adjuvant chemotherapy, or chemotherapy given concurrently with radiotherapy for non-metastatic disease, is allowed if the last dose was given 6 months or more before study entry.
  • Patients with recurrent disease after primary surgery and/or radiotherapy will be eligible.
  • For patients with previous radiotherapy, the indicator lesion(s) must not be within previous radiation field. The last dose of radiotherapy should be at least 3 weeks prior to study entry. The total radiotherapy received should not be more than 30% of the bone marrow.
  • Screening laboratory criteria:

WBC count > 3500/microl Neutrophils > 2000/microl Platelet count > 100,000/microl Hemoglobin > 9 g/dl (transfusion allowed)

Serum creatinine < 133 micromol/l, or Creatinine clearance > 30 ml/min, based on the Cockcroft formula (see section 5.1.1)

Bilirubin < 1.5 x upper limit of normal ALT/AST < 2 x upper limit of normal if liver metastases are absent < 5 x upper limit of normal if liver metastases are present

• Aged 18 years and above.
• Life expectancy > 3 months.
• Written informed consent.

Exclusion Criteria:

• • Patients with only evaluable disease.

  • Active uncontrolled infection.
  • Pregnant or lactating women.
  • Females of childbearing potential who are unwilling to avoid pregnancy, for the duration of the study.
  • Presence of any underlying medical conditions which in the investigators opinion would make the patient unsuitable for treatment.
  • Concomitant malignancies or previous malignancies other than NSCLC within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, carcinoma-in-situ of the cervix, or stage A low grade prostate cancer.
  • Patients with CNS and/or leptomeningeal metastases; unless asymptomatic and not receiving corticosteriod therapy.