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.