Combination Chemotherapy and Computer-Planned Radiation Therapy in Treating Patients With Unresectable Stage III Non-Small Cell Lung Cancer

• Overall Survival [ Time Frame: 6 years post treatment ] [ Designated as safety issue: No ]
• Toxicity [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
  Toxicity will be assessed during treatment

RATIONALE: Drugs used in chemotherapy 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. Computer systems that allow doctors to create a 3-dimensional picture of the tumor to plan treatment may result in more effective radiation therapy. It is not yet known which chemotherapy and/or radiation therapy regimen is more effective in treating non-small cell lung cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of different combination chemotherapy regimens and 3-dimensional radiation therapy in treating patients who have unresectable stage III non-small cell lung cancer.

OBJECTIVES:

• Compare the overall response rate, failure-free survival, and survival of patients with inoperable stage IIIA or IIIB non-small cell lung cancer treated with paclitaxel and carboplatin with concurrent 3-dimensional conformal radiotherapy (3-D XRT) vs gemcitabine and carboplatin with concurrent 3-D XRT.
• Compare the toxicity of these regimens in these patients.
• Compare the pattern of failure (locoregional vs distant failure) in patients treated with these regimens.
• Determine the feasibility of delivering 3-D XRT to patients in this multicenter study.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive paclitaxel IV over 1 hour followed by carboplatin IV over 30 minutes once weekly and 3-dimensional conformal radiotherapy (3-D XRT) once daily 5 days a week. Treatment repeats weekly for 7 courses.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive gemcitabine IV over 30 minutes twice weekly and 3-D XRT as in arm I. Treatment repeats weekly for 7 courses.

In both arms, treatment continues in the absence of disease progression.

Patients are followed every 2 months for 2 years, every 4 months for 2 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 82 patients (41 per treatment arm) will be accrued for this study within 9 months.

• Drug: carboplatin
  Arm A: AUC=6 IV over 30 min for 2 cycles then AUC=2 IV over 30 min q wk for 7 wks Arm B: AUC=5 IV over 30 min for 2 cycles
• Drug: gemcitabine hydrochloride
  1000 mg/sq m IV over 30 min days 1 & 8 repeat q 21 days for 2 cycles; then 35 mg/sq m IV over 30 min 2X wk for 7 wks
• Drug: paclitaxel
  225 mg/sq m IV over 3 hrs q 21 days for 2 cycles, then 45 mg/sq m IV over 1 hr q wk for 7 wks
• Radiation: radiation therapy
  3-D XRT 7400 cGy total after induction (during cycles 3-9)

• Experimental: Paclitaxel + Carboplatin
  Paclitaxel and carboplatin induction (2 cycles)followed by chemotherapy with the addition of radiotherapy for 7 cycles
  Interventions:

  • Drug: carboplatin
  • Drug: paclitaxel
  • Radiation: radiation therapy
• Experimental: Gemcitabine + Carboplatin
  Gemcitabine and carboplatin induction (2cycles) followed by chemotherapy with the addition of radiotherapy for 7 cycles
  Interventions:

  • Drug: carboplatin
  • Drug: gemcitabine hydrochloride
  • Radiation: radiation therapy

• Socinski MA, Blackstock AW, Bogart JA, Wang X, Munley M, Rosenman J, Gu L, Masters GA, Ungaro P, Sleeper A, Green M, Miller AA, Vokes EE. Randomized phase II trial of induction chemotherapy followed by concurrent chemotherapy and dose-escalated thoracic conformal radiotherapy (74 Gy) in stage III non-small-cell lung cancer: CALGB 30105. J Clin Oncol. 2008 May 20;26(15):2457-63.
• Blackstock AW, Socinski MA, Bogart J, et al.: Induction (Ind) plus concurrent (Con) chemotherapy with high-dose (74 Gy) 3-dimensional (3-D) thoracic radiotherapy (TRT) in stage III non-small cell lung cancer (NSCLC): preliminary report of Cancer and Leukemia Group B (CALGB) 30105. [Abstract] J Clin Oncol 24 (Suppl 18): A-7042, 374s, 2006.
• Blackstock AW, Socinski MA, Gu L, et al.: Initial pulmonary toxicity evaluation of chemoradiotherapy (CRT) utilizing 74 Gy 3-dimensional (3-D) thoracic radiation in stage III non-small cell lung cancer (NSCLC): a Cancer and Leukemia Group B (CALGB) randomized phase II trial. [Abstract] J Clin Oncol 23 (Suppl 16): A-7060, 635s, 2005.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  • Squamous cell carcinoma
  • Adenocarcinoma, including bronchoalveolar cell carcinoma
  • Large cell anaplastic carcinoma, including giant and clear cell carcinoma
• Inoperable stage IIIA or IIIB disease

• No direct invasion of vertebral body

  • Tumors adjacent to a vertebral body without bone invasion allowed if all gross disease can be encompassed in radiotherapy boost field
• Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in radiotherapy boost field
• No scalene, supraclavicular, or contralateral hilar node involvement

• Transudate, cytologically negative, non-bloody pleural effusion allowed if it can be encompassed in radiotherapy field

  • No exudative, bloody, or cytologically malignant pleural effusion
  • Evidence of pleural effusion by chest CT scan but not chest x-ray that is too small to tap allowed

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR
  • At least 10 mm by spiral CT scan

  • The following are not considered measurable disease:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
    • Tumor lesions in a previously irradiated field

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• AST less than 2 times upper limit of normal

Renal:

• Creatinine clearance 20-130 mL/min for females
• Creatinine clearance 20-150 mL/min for males

Pulmonary:

• FEV1 at least 1.2 L

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other currently active malignancy (defined as completed prior therapy and considered to be at less than 30% risk of relapse) except non-melanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except steroids for adrenal failure or septic shock, hormones for non-disease-related conditions (e.g., insulin for diabetes), or glucocorticosteroids as antiemetics

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy for NSCLC

Surgery:

• At least 2 weeks since prior exploratory thoracotomy