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February 27, 1981, Vol 245, No. 8 >
ARTICLE | February 27, 1981

Effect of Warfarin on Survival in Small Cell Carcinoma of the Lung: Title and subTitle BreakVeterans Administration Study No. 75 FREE

Leo R. Zacharski, MD; William G. Henderson, PhD; Frederick R. Rickles, MD; Walter B. Forman, MD; C. J. Cornell, Jr, MD; R. Jackson Forcier, MD; Richard Edwards, MD; Elwood Headley, MD; Sang-Hee Kim, MD; Joseph R. O'Donnell, MD; Robert O'Dell, MD; Karl Tornyos, MD; Hau C. Kwaan, MD
[+] Author Affiliations

Reprint requests to Veterans Administration Medical Center, White River Junction, VT 05001 (Dr Zacharski).


JAMA. 1981;245(8):831-835. doi:10.1001/jama.1981.03310330021017
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References

In a controlled, randomized study, survival of patients with small cell carcinoma of the lung (SCCL) was prolonged on addition of warfarin sodium to combination chemotherapy plus radiation therapy. Median survival for 25 control patients was 24 weeks and for 25 warfarin-treated patients was 50 weeks. This difference could not be accounted for by differences between groups in performance status, extent of disease, age, or sex. The survival advantage associated with warfarin administration was observed both for patients with extensive disease and for those who failed to achieve complete or partial remission. The warfarin-treated group also demonstrated a significantly increased time to first evidence of disease progression. These results suggest that warfarin may be useful in the treatment of SCCL and also support the hypothesis that the blood coagulation mechanism may be involved in the growth and spread of cancer in man.

(JAMA 1981;245:831-835)

REFERENCES

1 +
Zacharski LR, Henderson WG, Rickles FR, et al:  Rationale and experimental design for the VA Cooperative Study of anticoagulation (warfarin) in the treatment of cancer . Cancer 1979;; 44:732-741.
2 +
Eagan RT, Maurer LH, Forcier RJ, et al:  Small cell carcinoma of the lung: Staging, paraneoplastic syndromes, treatment and survival . Cancer 1974;;33:527-532.
3 +
Maurer LH, Tulloh M, Weiss RB, et al:  A randomized combined modality trial in small cell carcinoma of the lung . Cancer 1980;;45:30-39.
4 +
Kaplan EL, Meier P:  Non-parametric estimation from incomplete observations . J Am Stat Assoc 1958;;53:457-482.
5 +
Gehan EA:  A generalized Wilcoxon test for comparing arbitrarily singly-censored samples . Biometrika 1965;;52:203-223.
6 +
Kreyberg L: Histologic Typing of Lung Tumors . Geneva, World Health Organization, Geneva, 1967;.
7 +
Matthews MJ:  Morphologic classification of bronchiogenic carcinoma . Cancer Chemother Rep 1973;;4:299-301.
8 +
Zacharski LR:  Anticoagulation in the treatment of cancer in man , in Donati M, Davidson JF, Garattini S (eds): Malignancy and the Hemostatic System . New York, Raven Press, 1981;.
9 +
Stanford CF:  Anticoagulants in the treatment of small cell carcinoma of the bronchus . Thorax 1979;;34:113-116.
10 +
Bunn PA Jr, Cohen MH, Ihde DC, et al:  Review of therapeutic trials in small cell bronchogenic carcinoma of the lung , in Muggia F, Rozencweig M (eds): Lung Cancer: Progress in Therapeutic Research . New York, Raven Press, 1979;.
11 +
Hagmar B:  Cell surface change and metastasis formation . Acta Path Microbiol Scand 1972;;80:357-366.
12 +
Jamieson GG, Angove RC:  Heparinized chemotherapy in the treatment of disseminated lung cancer . Aust NZ J Med 1979;;9:381-384.
13 +
Ghosh BC, Cliffton EE:  Malignant tumors with superior vena cava obstruction . NY St J Med 1973;;73:281-286.
14 +
Jackson DV Jr, Richards F II, Cooper MR, et al:  Prophylactic cranial irradiation in small cell carcinoma of the lung: A randomized study . JAMA 1977;;237:2730-2733.
15 +
Livingston RB, Moore TN, Heilbrun L, et al:  Small cell carcinoma of the lung: Combined chemotherapy and radiation . Ann Intern Med 1978;;88:194-199.
16 +
Poggi A, Mussoni L, Kornblihtt L, et al:  Warfarin enantiomers, anticoagulation and experimental tumor metastasis . Lancet 1978;;1:163-164.
17 +
Brown JM:  A study of the mechanism by which anticoagulation with warfarin inhibits blood-borne metastases . Cancer Res 1973;; 33:1217-1224.
18 +
Zacharski LR, Rosenstein R:  Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy . Blood 1979;;53:366-374.
19 +
Wood S Jr:  Mechanism of establishment of tumor metastases , in Ioachim HL (ed): Pathobiology Annual . New York, Appleton-Century-Crofts, 1971;, pp 281-308.
20 +
Wattenberg LW, Lam LKT, Fladmoe AV:  Inhibition of chemical carcinogen-induced neoplasia by coumarins and α-angelica-lactone . Cancer Res 1979;;38:1651-1654.
21 +
Egilsson V:  Differentiation of malignant neuroblastoma cells: Evidence for a mitochondrial role . Cell Biol Int Rep 1977;;1:435-438.
22 +
Lowenbraun S, Bartolucci A, Smalley RV, et al:  The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma . Cancer 1979;;44:406-413.
23 +
Holyoke PY, Samuels ML, Smith T, et al:  Chemoimmunotherapy of small cell bronchiogenic carcinoma . Cancer 1978;;42:34-40.
24 +
Minna JD, Brereton HD, Cohen MH, et al.  The treatment of small cell carcinoma of the lung: Prospects for cure , in Muggia F, Rozencweig M (eds): Lung Cancer: Progress in Therapeutic Research . New York, Raven Press, 1979;.
25 +
Greco FA, Oldham RK:  Current concepts in cancer: Small-cell lung cancer . N Engl J Med 1979;;301:355-357.

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1 +
Zacharski LR, Henderson WG, Rickles FR, et al:  Rationale and experimental design for the VA Cooperative Study of anticoagulation (warfarin) in the treatment of cancer . Cancer 1979;; 44:732-741.
2 +
Eagan RT, Maurer LH, Forcier RJ, et al:  Small cell carcinoma of the lung: Staging, paraneoplastic syndromes, treatment and survival . Cancer 1974;;33:527-532.
3 +
Maurer LH, Tulloh M, Weiss RB, et al:  A randomized combined modality trial in small cell carcinoma of the lung . Cancer 1980;;45:30-39.
4 +
Kaplan EL, Meier P:  Non-parametric estimation from incomplete observations . J Am Stat Assoc 1958;;53:457-482.
5 +
Gehan EA:  A generalized Wilcoxon test for comparing arbitrarily singly-censored samples . Biometrika 1965;;52:203-223.
6 +
Kreyberg L: Histologic Typing of Lung Tumors . Geneva, World Health Organization, Geneva, 1967;.
7 +
Matthews MJ:  Morphologic classification of bronchiogenic carcinoma . Cancer Chemother Rep 1973;;4:299-301.
8 +
Zacharski LR:  Anticoagulation in the treatment of cancer in man , in Donati M, Davidson JF, Garattini S (eds): Malignancy and the Hemostatic System . New York, Raven Press, 1981;.
9 +
Stanford CF:  Anticoagulants in the treatment of small cell carcinoma of the bronchus . Thorax 1979;;34:113-116.
10 +
Bunn PA Jr, Cohen MH, Ihde DC, et al:  Review of therapeutic trials in small cell bronchogenic carcinoma of the lung , in Muggia F, Rozencweig M (eds): Lung Cancer: Progress in Therapeutic Research . New York, Raven Press, 1979;.
11 +
Hagmar B:  Cell surface change and metastasis formation . Acta Path Microbiol Scand 1972;;80:357-366.
12 +
Jamieson GG, Angove RC:  Heparinized chemotherapy in the treatment of disseminated lung cancer . Aust NZ J Med 1979;;9:381-384.
13 +
Ghosh BC, Cliffton EE:  Malignant tumors with superior vena cava obstruction . NY St J Med 1973;;73:281-286.
14 +
Jackson DV Jr, Richards F II, Cooper MR, et al:  Prophylactic cranial irradiation in small cell carcinoma of the lung: A randomized study . JAMA 1977;;237:2730-2733.
15 +
Livingston RB, Moore TN, Heilbrun L, et al:  Small cell carcinoma of the lung: Combined chemotherapy and radiation . Ann Intern Med 1978;;88:194-199.
16 +
Poggi A, Mussoni L, Kornblihtt L, et al:  Warfarin enantiomers, anticoagulation and experimental tumor metastasis . Lancet 1978;;1:163-164.
17 +
Brown JM:  A study of the mechanism by which anticoagulation with warfarin inhibits blood-borne metastases . Cancer Res 1973;; 33:1217-1224.
18 +
Zacharski LR, Rosenstein R:  Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy . Blood 1979;;53:366-374.
19 +
Wood S Jr:  Mechanism of establishment of tumor metastases , in Ioachim HL (ed): Pathobiology Annual . New York, Appleton-Century-Crofts, 1971;, pp 281-308.
20 +
Wattenberg LW, Lam LKT, Fladmoe AV:  Inhibition of chemical carcinogen-induced neoplasia by coumarins and α-angelica-lactone . Cancer Res 1979;;38:1651-1654.
21 +
Egilsson V:  Differentiation of malignant neuroblastoma cells: Evidence for a mitochondrial role . Cell Biol Int Rep 1977;;1:435-438.
22 +
Lowenbraun S, Bartolucci A, Smalley RV, et al:  The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma . Cancer 1979;;44:406-413.
23 +
Holyoke PY, Samuels ML, Smith T, et al:  Chemoimmunotherapy of small cell bronchiogenic carcinoma . Cancer 1978;;42:34-40.
24 +
Minna JD, Brereton HD, Cohen MH, et al.  The treatment of small cell carcinoma of the lung: Prospects for cure , in Muggia F, Rozencweig M (eds): Lung Cancer: Progress in Therapeutic Research . New York, Raven Press, 1979;.
25 +
Greco FA, Oldham RK:  Current concepts in cancer: Small-cell lung cancer . N Engl J Med 1979;;301:355-357.

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