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

L. Herbert Maurer, James E. Herndon, Donna R. Hollis, Joseph Aisner, Robert W. Carey, Arthur T. Skarin, Michael C. Perry, Walter L. Eaton, Leo L. Zacharski, Susan Hammond, Mark R. Green

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Abstract

Purpose: Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of Warfarin to chemotherapy might enhance response and/or survival in small- cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. Patients and Methods: Patients were randomized to receive warfarin ar no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. Results: There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin- treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with ≤ 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P =.103). Conclusion: Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.

Original languageEnglish (US)
Pages (from-to)3378-3387
Number of pages10
JournalJournal of Clinical Oncology
Volume15
Issue number11
DOIs
StatePublished - Jan 1 1997

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Small Cell Lung Carcinoma
Warfarin
Leukemia
Radiotherapy
Drug Therapy
Neoplasms
Survival
Etoposide
Cyclophosphamide
United States Department of Veterans Affairs
Therapeutics
Doxorubicin
Anticoagulants
Cisplatin
Population
Disease-Free Survival
Survival Rate
Recurrence
Lung
Control Groups

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Maurer, L. Herbert ; Herndon, James E. ; Hollis, Donna R. ; Aisner, Joseph ; Carey, Robert W. ; Skarin, Arthur T. ; Perry, Michael C. ; Eaton, Walter L. ; Zacharski, Leo L. ; Hammond, Susan ; Green, Mark R. / 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. In: Journal of Clinical Oncology. 1997 ; Vol. 15, No. 11. pp. 3378-3387.
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title = "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",
abstract = "Purpose: Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of Warfarin to chemotherapy might enhance response and/or survival in small- cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. Patients and Methods: Patients were randomized to receive warfarin ar no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. Results: There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin- treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with ≤ 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P =.103). Conclusion: Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.",
author = "Maurer, {L. Herbert} and Herndon, {James E.} and Hollis, {Donna R.} and Joseph Aisner and Carey, {Robert W.} and Skarin, {Arthur T.} and Perry, {Michael C.} and Eaton, {Walter L.} and Zacharski, {Leo L.} and Susan Hammond and Green, {Mark R.}",
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Maurer, LH, Herndon, JE, Hollis, DR, Aisner, J, Carey, RW, Skarin, AT, Perry, MC, Eaton, WL, Zacharski, LL, Hammond, S & Green, MR 1997, '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', Journal of Clinical Oncology, vol. 15, no. 11, pp. 3378-3387. https://doi.org/10.1200/JCO.1997.15.11.3378

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. / Maurer, L. Herbert; Herndon, James E.; Hollis, Donna R.; Aisner, Joseph; Carey, Robert W.; Skarin, Arthur T.; Perry, Michael C.; Eaton, Walter L.; Zacharski, Leo L.; Hammond, Susan; Green, Mark R.

In: Journal of Clinical Oncology, Vol. 15, No. 11, 01.01.1997, p. 3378-3387.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized trial of chemotherapy and radiation therapy with or without Warfarin for limited-stage small-cell lung cancer

T2 - A cancer and leukemia group B study

AU - Maurer, L. Herbert

AU - Herndon, James E.

AU - Hollis, Donna R.

AU - Aisner, Joseph

AU - Carey, Robert W.

AU - Skarin, Arthur T.

AU - Perry, Michael C.

AU - Eaton, Walter L.

AU - Zacharski, Leo L.

AU - Hammond, Susan

AU - Green, Mark R.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Purpose: Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of Warfarin to chemotherapy might enhance response and/or survival in small- cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. Patients and Methods: Patients were randomized to receive warfarin ar no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. Results: There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin- treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with ≤ 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P =.103). Conclusion: Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.

AB - Purpose: Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of Warfarin to chemotherapy might enhance response and/or survival in small- cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. Patients and Methods: Patients were randomized to receive warfarin ar no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. Results: There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin- treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with ≤ 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P =.103). Conclusion: Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.

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