• Overall survival every 3 months [ Designated as safety issue: No ]
  

• Progression-free survival every 3 months [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the overall survival of patients with unresectable stage IIIA or IIIB non-small cell lung cancer treated with induction platinum-based chemotherapy and radiotherapy with or without AE-941 (Neovastat).
• Determine the progression-free survival, tumor response, tumor response duration, and metastasis-free survival of patients treated with these regimens.
• Determine the tolerability of this regimen in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to stage (IIIA vs IIIB), type of platinum-based induction chemotherapy to be received (cisplatin and vinorelbine vs carboplatin and paclitaxel), and gender. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
• Arm II: Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.

All patients receive induction chemotherapy with 1 of the following platinum-based regimens:

• Cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78
• Carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85 All patients receive radiotherapy beginning on day 50 for 6 weeks.

Treatment in both arms continues in the absence of unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 756 patients (378 per treatment arm) will be accrued for this study within 36 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed newly diagnosed, untreated, unresectable stage IIIA or stage IIIB non-small cell lung cancer

  • Squamous cell carcinoma, adenocarcinoma, or large cell carcinoma of the lung
  • Mixed tumors allowed if non-small cell elements identified
  • Contralateral supraclavicular and/or scalene lymph node involvement allowed
  • No disease extending into the cervical region
• At least 1 bidimensionally or unidimensionally measurable lesion
• No pleural effusion unless cytologically negative or too small to safely aspirate
• Not scheduled for curative cancer surgery

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• Hematocrit greater than 30%

Hepatic:

• SGOT or SGPT less than 1.5 times upper limit of normal
• Bilirubin normal

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Other:

• No other major medical or psychiatric illness that would preclude study participation or consent
• No medical condition that interferes with oral medication intake and/or absorption (gastrectomy or major intestinal resection)
• No grade 2 or greater peripheral neuropathy unless secondary to mechanical etiology
• No hypersensitivity to fish products
• No more than 10% weight loss within past 3 months
• No other malignancy within past 3 years except inactive carcinoma in situ of the cervix or nonmelanoma skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 30 days since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics
• Recovered from prior major surgery

Other:

• At least 30 days since prior shark cartilage products
• No other concurrent investigational anticancer agents
• No other concurrent cartilage products
• No other concurrent investigational agents
• No concurrent amifostine or other radioprotectants
• No concurrent enrollment in other clinical trials