Neoadjuvant or Adjuvant Chemotherapy in Patients With Operable Non-small-cell Lung Cancer

Randomized Trial of Surgery With or Without Paclitaxel Plus Carboplatin as Neoadjuvant or Adjuvant Chemotherapy in Patients With Operable, Non-small-cell Lung Cancer

Open-label multicenter randomized Phase III trial.

Randomized trial of surgery with or without Paclitaxel (taxol) plus Carboplatin as neoadjuvant or adjuvant chemotherapy in patients with operable, non-small-cell lung cancer.

Inclusion Criteria:

• The patients eligible for the study are those with a diagnosis, histologically or cytologically proven, of NSCLC without metastases at stages IB, IIA, IIB and IIIA (not N2) of the disease. Patients with stage IA and tumor size >2cm will be eligible as well.
• Patients aged > 18 years.
• Tumor considered resectable by the attending surgeon.
• The patient must have an ECOG *2 or Karnofsky >60%.
• The patients need to have adequate hematological, renal and hepatic function defined as:

Absolute neutrophil counts (ANC*) *1.5 x 109/L Platelet counts *100 x 109/L Total bilirubin *1.25 x upper limit of normal distribution Serum creatinine <120 umol/L (<1.5 mg/dl) Creatinine clearance >60 ml/min

• ANC = segmented neutrophils + banded neutrophils

  • The patients should have recovered from any serious surgical sequellae.
  • Informed consent must be obtained from the patient in accordance with the requirements of the IRB/EC.
  • If female, the patient must not be pregnant or breast-feeding. Women of child bearing potential need to have a pregnancy test performed and to take appropriate contraceptive action during the period of the study.
  • Operability criteria: Lung function test will be performed so as to confirm a predictive postoperative value of FEV-1 >-800 ml, i.e. correct homeostasis. A carbon monoxide diffusion test is to be conducted and, when applicable, repeated following the induction treatment while taking into account the sensitivity of post-chemotherapy pulmonary toxicity detection.

Exclusion Criteria:

• Patients who have previously been treated with chemotherapy and/or radiotherapy.
• History of significant cardiovascular disease such as non-controlled hypertension, unstable angina or congestive heart failure even if these are controlled by medication. Documented history of acute myocardial infarction in the previous year, ventricular arrhythmias that required medication or 2nd or 3rd atrial-ventricular blocks.
• Pre-existing sensory or motor neurotoxicity grade >2 based on the WHO criteria.
• Active infection or other clinical state that could seriously reduce the patient's capacity to tolerate the treatment protocol, including previous allergic reactions to products containing Cremophor (e.g. cyclosporin or vitamin K).
• Previous or concomitant malignant tumor (with the exception of in situ cervical carcinoma, baso-cellular carcinoma, squamous cell skin carcinoma or urothelial superficial carcinoma) which are considered potentially curable with oncological treatment and have a disease free survival (DFS) greater than 5 years EXCEPTING breast cancer, melanoma and hypernephroma
• Marked psychoses or senility