Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over NCI CLB-8534 CALGB-8534

Objectives

I.  Determine CR rates and long-term survival of patients with limited small 
cell carcinoma of the lung treated with a combined modality therapeutic 
program consisting of three courses of ACE chemotherapy 
(adriamycin/cyclophosphamide/VP-16213) followed by two courses of PCE 
chemotherapy (cis-platinum/adriamycin/VP-16213) plus primary thoracic and 
prophylactic cranial radiotherapy.
II.  Determine whether the addition of warfarin throughout this combined 
modality regimen improves the response rate and long-term survival of these 
patients.
III.  Evaluate the neuropsychiatric effects of the new combined modality 
program with regard to cognitive functioning and mood in these patients.

Entry Criteria

Disease Characteristics:

Histologically (preferable) or cytologically proven small
cell anaplastic undifferentiated carcinoma of the bronchus

Limited disease required, i.e.:
  Confined to one hemithorax
  With or without mediastinal nodes
  With or without bilateral supraclavicular nodes

No ipsilateral pleural effusions (whether cytologically
positive or not)

Measurable disease required

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy

Surgery:
  No prior surgical resection

Patient Characteristics:

Age:
  18 and over

Performance status:
  CALGB 0-2

Life expectancy:
  More than 2 months

Hematopoietic:
  AGC more than 1,800
  Platelets more than 100,000
  Hgb more than 10 g/dl

Hepatic:
  Bilirubin less than 1.5 mg/dl
  No biliary obstruction
  PT more than 16 seconds for at least 7 days excludes

Renal:
  BUN less than 1.5 x normal
  Creatinine less than 1.8 g/dl
  Creatinine clearance more than 60 ml/min

Cardiovascular:
  No severe uncontrolled cardiovascular disease, i.e.:
     No MI within 6 months prior to entry
     No CHF
     No severe angina
  No severe hypertension (diastolic pressure over 115 mm Hg
  on at least 3 successive occasions)

Other:
  No contraindication to warfarin use, including:
     Active GI bleeding or peptic ulcer within 6 months
     Other internal bleeding
     Prior intracranial hemorrhage
     Any hereditary hemorrhagic disorder
     Acute pancreatitis
     Allergy or idiosyncratic reaction to warfarin
  Adequate nutritional status required
  No other medical indication for warfarin therapy
  No second malignancy except:
     Curatively treated carcinoma in situ of the cervix
     Basal cell carcinoma of the skin
  No pregnant women

Expected Enrollment

The study will require that 370 patients be entered over about 3.75 years.

Outline

Randomized study.  Because of excessive fatal pulmonary toxicity, the 3 
post-radiotherapy courses of chemotherapy that were originally planned for 
this protocol have been deleted.  Patients currently receiving courses 6, 7, 
or 8 should have treatment terminated immediately.
Arm I:  3-Drug Combination Chemotherapy followed by 3-Drug Combination 
Chemotherapy plus Radiotherapy.  ACE:  Adriamycin, ADR, NSC-123127; 
Cyclophosphamide, CTX, NSC-26271; VP-16213, VP-16, NSC-141540; followed by 
PCE:  cis-Platinum, CDDP, NSC-119875; ADR; VP-16; plus irradiation of the 
primary tumor and ipsilateral hilar and mediastinal lymph nodes and 
prophylactic whole-brain radiotherapy using Co60 equipment or accelerator 
beams of 4-10 MeV.
Arm II:  3-Drug Combination Chemotherapy followed by 3-Drug Combination 
Chemotherapy plus Radiotherapy with Continuous Anticoagulation Therapy.  ACE 
followed by PCE plus Radiotherapy as in Arm I; with Warfarin, WARF.

Maurer LH, Herndon JE 2nd, Hollis DR, et al.: Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study. J Clin Oncol 15 (11): 3378-87, 1997.[PUBMED Abstract]

Maurer LH, Herdon JE, Hollis DR, et al.: A randomized trial of chemotherapy (CT) and radiation therapy (RT) with or without warfarin (W) for limited disease (LD) small cell lung cancer (SCLC) - CALGB 8534. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-1119, 335, 1993.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

L. Maurer, MD, Protocol chair(Contact information may not be current)		Ph: 603-653-9000; 800-639-6918