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 II, Phase I Treatment Closed over 21 NCI CLB-8532 CALGB-8532

Objectives

I.  Determine whether combined modality therapy with 3 courses of ACE 
(adriamycin/cyclophosphamide/VP-16213) followed by PCE 
(cis-platinum/cyclophosphamide/VP-16213) administered concomitantly with local 
chest irradiation and prophylactic cranial irradiation followed by 3 courses 
of ACE is technically feasible in terms of toxicity, local complications, and 
an acceptable CR rate in patients with limited small cell lung cancer.
II.  Determine whether warfarin can be given concomitantly with the above 
therapy.
III.  Assess the toxicity of PCE chemotherapy combined with chest irradiation 
after 3 courses of ACE in these patients.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients over the age of 21 years 
with measurable or evaluable, histologically (preferred) or cytologically 
confirmed small cell anaplastic, undifferentiated bronchogenic carcinoma 
provided that disease is limited to one hemithorax with or without mediastinal 
nodes or with or without bilateral supraclavicular node involvement.  The 
presence of a pleural effusion, whether cytologically positive or negative, 
excludes.  Patients must not have received prior surgical resection, 
chemotherapy, or radiotherapy, and there must have been no antecedent 
indication for current warfarin therapy.  There must be laboratory evidence of 
adequate liver, kidney, and bone marrow function, and patients must have 
adequate nutritional status, a performance status of 0-2, and a life 
expectancy of greater than 2 months.  Aside from curatively treated carcinoma 
in situ of the cervix and basal cell skin cancer, there may be no previous or 
concurrent second malignancy.  Patients must be free from uncontrolled or 
severe cardiovascular disease including myocardial infarction within 6 months, 
congestive heart failure, and severe angina (patients with persistent EKG 
abnormalities from a myocardial infarction more than 6 months prior to 
admission are eligible).  The following contraindications to anticoagulant 
therapy exclude:  active GI bleeding or peptic ulcer within 6 months, other 
internal bleeding, prior intracranial hemorrhage, hereditary hemorrhagic 
disorder, acute pancreatitis, biliary obstruction, severe hypertension, 
allergy or idiosyncratic reaction to warfarin, and PT of greater than 16 
seconds for at least 7 days.  Pregnancy excludes.

Expected Enrollment

65 patients will be entered over about 8 months.  Per April 1985 activation 
amendment, this study will initially be piloted at a limited number of 
institutions.  20 patients will be entered initially.  When 10 of these 
patients have completed Regimen B, the data will be reviewed; if toxicity is 
acceptable, the study will then be opened to group-wide participation and will 
accrue an additional 45-50 patients for a total of 65 entries.

Outline

Nonrandomized study.  After 3 courses of Induction therapy, responders and 
those with stable disease enter Regimen B; those with objective evidence of 
response also receive prophylactic cranial irradiation on Regimen C 
concurrently and then return to Regimen A for 3 courses.
Regimen A:  Induction.  3-Drug Combination Chemotherapy plus Anticoagulant 
Therapy.  ACE:  Adriamycin, ADR, NSC-123127; Cyclophosphamide, CTX, NSC-26271; 
VP-16213, VP-16, NSC-141540; plus Warfarin, NSC-59813.
Regimen B:  3-Drug Combination Chemotherapy plus Radiotherapy followed by 
3-Drug Combination Chemotherapy plus Anticoagulant Therapy.  PCE:  
cis-Platinum, CACP, NSC-119875; CTX; VP-16; plus involved-field chest 
irradiation using Co60 or accelerator beams with nominal energy of 4-10 MeV; 
followed by ACE; plus Warfarin.
Regimen C:  Radiotherapy.  Prophylactic whole-brain irradiation using Co60 or 
accelerator beams of 4-10 MeV.

Aisner J, Propert K, Perry M, et al.: Aggressive combination chemotherapy, chest and brain irradiation, and warfarin for the treatment of limited disease small cell lung cancer (SCLC). [Abstract] Proceedings of the American Society of Clinical Oncology 6: A-707, 179, 1987.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Joseph Aisner, MD, Protocol chair		Ph: 732-235-7401 Email: aisnerjo@umdnj.edu