RATIONALE: Drugs used in chemotherapy, such as docetaxel and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving chemotherapy with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known if chemotherapy plus radiation therapy is more effective than chemotherapy alone before surgery in treating non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying docetaxel and cisplatin with or without radiation therapy to see how well they work when given before surgery in treating patients with stage IIIA non-small cell lung cancer that has spread to lymph nodes in the chest.
The main objective of this trial is to compare feasibility and efficacy of sequential neoadjuvant chemoradiotherapy with 44 Gy concomitant boost to neoadjuvant chemotherapy alone. Secondary objectives are to assess the value of PET in predicting pathological response and eventfree survival in stage IIIA NSCLC, and a health economic analysis of the two regimens. Further to compare the amount of serum DNA in patients with stage IIIA, pN2 NSCLC before chemotherapy, before surgery and at the second follow-up visit (i.e. four months after surgery or treatment failure for patients who can not be operated) in patients randomized into the trial SAKK 16/00 and to correlate the DNA variation with tumor response, remission duration and overall survival. OUTLINE: This is a prospective randomized phase III trial. Patients are stratified according to mediastinal bulk (5 cm or more vs less than 5 cm), weight loss in the past 6 months (5% or more vs less than 5%), and participating center. Patients are randomized to 1 of 2 treatment arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
232
Docetaxel (Taxotere®) 85 mg/m2 1 hour iv infusion d1 Cisplatin 100 mg/m2 1 hour iv infusion d1 Schedule: 3 cycles repeated every 21 days
Radiotherapy (3 weeks after last chemotherapy administration) 44 Gy in 22 fractions concomitant boost technique in 3 weeks
3-4 weeks after termination of radiotherapy
Klinik Loewenstein gGmbH
Löwenstein, Germany
Klinikum der Stadt Mannheim
Mannheim, Germany
Institut za plucne bolesti
Kamenitz, Serbia
Institute of Oncology
Kamenitz, Serbia
Kantonsspital Aarau
Aarau, Switzerland
Kantonsspital Baden
Baden, Switzerland
Kantonsspital
Baden, Switzerland
Saint Claraspital AG
Basel, Switzerland
Universitaetsspital-Basel
Basel, Switzerland
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
Bellinzona, Switzerland
...and 15 more locations
Event-free survival
Time from randomization to relapse/progression/second tumor/death, whichever occurs first (for all randomized patients). If no event is observed, the patients will be censored at the last time they were known to be alive.
Time frame: 1 month after surgery
Postoperative mortality assessed
All deaths occurring within 30 days of the thoracic surgery to remove the primary tumor
Time frame: 1 month after surgery
Toxicity (hematological, renal and neurological toxicities, nausea and vomiting, weight changes as well as esophageal toxicities)
Assessed according to the NCIC-CTG Expanded Common Toxicity Criteria grading. Special attention shall be given to hematological, renal and neurological toxicities, nausea and vomiting, weight changes as well as esophageal toxicities.
Time frame: During treatment
Complete resection rate after surgery
Assessed according to the NCIC-CTG Expanded Common Toxicity Criteria grading.
Time frame: 1 month after surgery
Objective response rate measured after completion of chemoradiotherapy
Response rate will be evaluated according to the 1. WHO response criteria 2. TNM classification after surgery.
Time frame: 43 days
Operability
Patients who are able to undergo radical resection of their lung cancer after neoadjuvant therapy, as assessed by the thoracic surgeon.
Time frame: 1 month after chemo
Overall survival
Calculated from randomization to the date of death from any cause. Patients not experiencing an event will be censored at the last time they were known to be alive.
Time frame: Life-long follow-up until death of patient (up to 30 years)
Failure pattern
Defined as location of first tumor progression or relapse. Failure can be local relapse (area of primary tumor or mediastinum), distant relapse (all others) or the combination thereof.
Time frame: Life-long follow-up until death of patient (up to 30 years)
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