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

Objectives of study:

1. to compare the response rate of carboplatin and constant rate infusion gemcitabine to the response rate of gemcitabine given in the standard 30-minute infusion
2. to compare the toxicity experience in both arms
3. To compare the time to progression in both study arms, and overall survival
4. To compare the quality of life on both study arms using the EORTC QLQ-C30 and QLQ-LC13.

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)