RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating advanced non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of three different combination chemotherapy regimens in treating patients who have advanced non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
stage IV non-small cell lung cancer Recurrent Small Cell Lung Cancer stage IIIB non-small cell lung cancer Quality of Life	Drug: cisplatin  Drug: gemcitabine  Drug: paclitaxel	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the overall survival between paclitaxel/cisplatin (arm I), gemcitabine/cisplatin (arm II), and paclitaxel/gemcitabine (arm III) in patients with advanced non-small cell lung cancer.

II. Determine the response rate, duration of response, progression-free survival, toxicity, and quality of life of these patients randomized in these three treatment arms.

PROTOCOL OUTLINE: This is randomized, multicenter study. Patients are stratified according to performance status (0-1 vs 2) and stage of disease (locally advanced vs metastatic).

Patients are randomized to receive paclitaxel IV over 3 hours on day 1 followed by cisplatin IV on day 1 every 3 weeks (arm I), gemcitabine IV over 30-60 minutes on days 1 and 8 and cisplatin IV on day 1 every 3 weeks (arm II), or paclitaxel IV over 3 hours on day 1 followed by gemcitabine IV over 30-60 minutes on days 1 and 8 every 3 weeks (arm III). Patients receive at least 2 courses of treatment. In the absence of unacceptable toxicity and disease progression, patients may receive up to 6 courses of treatment.

Quality of life is assessed before, during, and at the end of treatment, then every 6 weeks until disease progression, and then every 3 months until death.

Patients are followed every 6 weeks until disease progression, then every 3 months until death.

PROJECTED ACCRUAL: A total of 450 patients (150 patients per arm) will be accrued into this study over 36 months.

Ages Eligible for Study:  18 Years   -   75 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed advanced non-small cell lung cancer that is progressive within 2 months prior to study entry
• Stage IIIB due to malignant pleural effusion or supraclavicular lymph node involvement only
• Stage IV
• At least 1 bidimensionally or unidimensionally measurable target lesion
• Brain metastases or leptomeningeal disease that have been treated with radiotherapy, is stable without medications (e.g., steroids), and asymptomatic are allowed

--Prior/Concurrent Therapy--

• Biologic therapy: At least 4 weeks since prior immunotherapy; No concurrent colony stimulating factor except for secondary prophylaxis in case of infection and severe neutropenia; No concurrent immunotherapy
• Chemotherapy: No prior chemotherapy for advanced disease, including intracavitary chemotherapy; At least 1 year since prior neoadjuvant or adjuvant chemotherapy; No concurrent chemotherapy
• Endocrine therapy: See Disease Characteristics; No concurrent hormonal agents (except corticosteroids for antiemetic prophylaxis)
• Radiotherapy: Prior radiotherapy should not include all target lesions for evaluation; At least 4 weeks since prior radiotherapy; Concurrent palliative radiotherapy allowed if indicator lesion is outside of radiation field
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 to 75
• Performance status: WHO 0-2
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 2,000/mm3; Platelet count at least 100,000/mm3; Prothrombin time less than 1.5 times normal
• Hepatic: Bilirubin no greater than 1.25 times upper limit of normal (ULN) (no greater than 2.5 times ULN if due to liver metastases); AST or ALT less than 3 times ULN (no greater than 5 times ULN if due to liver metastases)
• Renal: Creatinine clearance at least 60 mL/min
• Cardiovascular: No uncontrolled cardiac disease, sign of cardiac failure, or rhythm disturbances requiring medication; No myocardial infarction in the past 3 months
• Neurological: No preexisting motor or sensory neurotoxicity of grade 2 or greater
• Other: No active uncontrolled infection; Not a poor medical risk due to nonmalignant disease; No secondary primary malignancy in the past 5 years (excluding melanoma, breast cancer, and hypernephroma) except carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin; No psychological condition that might hamper compliance in this study; Not pregnant; Effective contraception required of all fertile patients during and for 3 months after study

Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
Czech Republic
      University Hospital Bulovka, Krhanice,  257 42,  Czech Republic
Egypt
      National Cancer Institute of Egypt, Cairo,  Egypt
France
      CHRU de Nancy - Hopitaux de Brabois, Vandoeuvre-les-Nancy,  54511,  France
Germany
      Thoraxklinik Rohrbach, Heidelberg,  D-69126,  Germany
Greece
      Hippokration General Hospital of Athens, Athens,  GR-11527,  Greece
Italy
      Ospedale degli Infermi, Biella,  13900,  Italy
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands
      Academisch Ziekenhuis der Vrije Universiteit, Amsterdam,  1117 MB,  Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands
      Academisch Ziekenhuis Utrecht, Utrecht,  3508 GA,  Netherlands
      Arnhems Radiotherapeutisch Instituut, ARNHEM,  6815 AD,  Netherlands
      Catharina Ziekenhuis, Eindhoven,  5602 ZA,  Netherlands
      Elkerliek Ziekenhuis, Helmond,  5707-HA,  Netherlands
      Gelre Ziekenhuizen - Lokatie Lukas, Apeldoorn,  7334 DZ,  Netherlands
      Groot Ziekengasthuis 's-Hertogenbosch, 's-Hertogenbosch,  5211 NL,  Netherlands
      Leiden University Medical Center, Leiden,  2300 ZA,  Netherlands
      Leyenburg Ziekenhuis, 's-Gravenhage (Den Haag, The Hague),  2545 CH,  Netherlands
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands
      Rijnland Ziekenhuis, Leiderdorp,  2350 CC,  Netherlands
      Sint Antonius Ziekenhuis, Nieuwegein,  3435 CM,  Netherlands
      Sophia Ziekehuis, Zwolle,  8000 GK,  Netherlands
      St. Maartens Gasthuis, Venlo,  5900 BX,  Netherlands
      University Hospital - Rotterdam Dijkzigt, Rotterdam,  3000 CA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6252 HB,  Netherlands
      Ziekenhuis de Baronie, Breda,  4810 EV,  Netherlands
      Ziekenhuis de Heel, Zaandam,  1502 DV,  Netherlands
      Ziekenhuis St Jansdal, Harderwijk,  3840 AC,  Netherlands
Poland
      Maritime Hospital, Gdynia,  PL-81--519,  Poland
South Africa
      Medical Oncology Centre of Rosebank, Johannesburg,  2193,  South Africa
Spain
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain
      Hospital Universitario de Getafe, Madrid,  Spain
Switzerland
      Ospedale San Giovanni, Bellinzona,  CH-6500,  Switzerland

Study chairs or principal investigators

Egbert F. Smit,  Study Chair,  EORTC Lung Cancer Cooperative Group   

Study ID Numbers:  CDR0000066658; EORTC-08975
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003589
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08