Skip Navigation

JNCI Journal of the National Cancer Institute 2000 92(12):977-986; doi:10.1093/jnci/92.12.977
© 2000 by Oxford University Press
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by van Zandwijk, N.
Right arrow Articles by van Tinteren, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Zandwijk, N.
Right arrow Articles by van Tinteren, H.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Journal of the National Cancer Institute, Vol. 92, No. 12, 977-986, June 21, 2000
© 2000 Oxford University Press

EUROSCAN, a Randomized Trial of Vitamin A and N-Acetylcysteine in Patients With Head and Neck Cancer or Lung Cancer

Nico van Zandwijk, Otilia Dalesio, Ugo Pastorino, Nico de Vries, Harm van Tinteren, For the European Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups

Affiliations of authors: N. van Zandwijk, O. Dalesio, H. van Tinteren, The Netherlands Cancer Institute, Amsterdam; U. Pastorino, European Institute of Oncology, Milan, Italy; N. de Vries, St. Lucas Hospital, Amsterdam.

Correspondence to: Nico van Zandwijk, M.D., Ph.D., The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (e-mail: zandwijk{at}nki.nl).

Background: Preclinical evidence suggests that retinoids and antioxidants may prevent or delay the occurrence of cancer in the upper or lower airways, but such effects have not been reliably established in clinical studies. To assess the chemopreventive effects of vitamin A (retinyl palmitate) and N-acetylcysteine, we conducted a large randomized intervention study in patients with head and neck cancer or with lung cancer, most of whom had a history of smoking. Methods: From June 1988 through July 1994, a total of 2592 patients (60% with head and neck cancer and 40% with lung cancer) were randomly assigned to receive 1) retinyl palmitate (300000 IU daily for 1 year followed by 150000 IU for a 2nd year), 2) N-acetylcysteine (600 mg daily for 2 years), 3) both compounds, or 4) no intervention. All statistical tests were two-sided. Results: Of the patients, 93.5% had smoked tobacco at sometime in their lives (and 25% continued to smoke after cancer diagnosis). After a median follow-up of 49 months, 916 patients were reported with an event (recurrence, second primary tumor, or death). No statistically significant difference was observed in overall survival or event-free survival between patients who received retinyl palmitate and patients who did not. Similarly, no difference was seen in overall survival or event-free survival between patients who received N-acetylcysteine and patients who did not. There was a lower incidence of second primary tumors in the no intervention arm, but the difference was not statistically significant. Conclusion: A 2-year supplementation of retinyl palmitate and/or N-acetylcysteine resulted in no benefit—in terms of survival, event-free survival, or second primary tumors—for patients with head and neck cancer or with lung cancer, most of whom were previous or current smokers.



Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
Cancer Prevention ResearchHome page
L. J. Wirth, J. F. Krane, Y. Li, M. Othus, A. E. Moran, D. M. Dorfman, C. M. Norris Jr, L. Goguen, M. R. Posner, R. I. Haddad, et al.
A Pilot Surrogate Endpoint Biomarker Study of Celecoxib in Oral Premalignant Lesions
Cancer Prevention Research, October 1, 2008; 1(5): 339 - 348.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
W. N. Hittelman, D. D. Liu, J. M. Kurie, R. Lotan, J. S. Lee, F. Khuri, H. Ibarguen, R. C. Morice, G. Walsh, J. A. Roth, et al.
Proliferative Changes in the Bronchial Epithelium of Former Smokers Treated With Retinoids
J Natl Cancer Inst, November 7, 2007; 99(21): 1603 - 1612.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
J. Gray, J. T. Mao, E. Szabo, M. Kelley, J. Kurie, and G. Bepler
Lung Cancer Chemoprevention: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)
Chest, September 1, 2007; 132(3_suppl): 56S - 68S.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
A. A. Davies, G. Davey Smith, R. Harbord, G. E. Bekkering, J. A. C. Sterne, R. Beynon, and S. Thomas
Nutritional interventions and outcome in patients with cancer or preinvasive lesions: systematic review.
J Natl Cancer Inst, July 19, 2006; 98(14): 961 - 973.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
K. El-Bayoumy, A. Das, B. Narayanan, N. Narayanan, E. S. Fiala, D. Desai, C. V. Rao, S. Amin, and R. Sinha
Molecular targets of the chemopreventive agent 1,4-phenylenebis (methylene)-selenocyanate in human non-small cell lung cancer
Carcinogenesis, July 1, 2006; 27(7): 1369 - 1376.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
G. J. Kelloff, S. M. Lippman, A. J. Dannenberg, C. C. Sigman, H. L. Pearce, B. J. Reid, E. Szabo, V. C. Jordan, M. R. Spitz, G. B. Mills, et al.
Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer--A Plan to Move Forward
Clin. Cancer Res., June 15, 2006; 12(12): 3661 - 3697.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
F. R. Khuri, J. J. Lee, S. M. Lippman, E. S. Kim, J. S. Cooper, S. E. Benner, R. Winn, T. F. Pajak, B. Williams, G. Shenouda, et al.
Randomized Phase III Trial of Low-dose Isotretinoin for Prevention of Second Primary Tumors in Stage I and II Head and Neck Cancer Patients.
J Natl Cancer Inst, April 5, 2006; 98(7): 441 - 450.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
A. L. Sabichi, X. Xu, and S. M. Lippman
RAR{beta}1': Primed To Fight Retinoid Resistance in Lung Carcinogenesis
J Natl Cancer Inst, November 16, 2005; 97(22): 1632 - 1633.
[Full Text] [PDF]


Home page
JCOHome page
F. R. Hirsch and S. M. Lippman
Advances in the Biology of Lung Cancer Chemoprevention
J. Clin. Oncol., May 10, 2005; 23(14): 3186 - 3197.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
E. S. Kim and W. K. Hong
An Apple a Day...Does It Really Keep the Doctor Away? The Current State of Cancer Chemoprevention
J Natl Cancer Inst, April 6, 2005; 97(7): 468 - 470.
[Full Text] [PDF]


Home page
Toxicol SciHome page
H. Witschi
Carcinogenic Activity of Cigarette Smoke Gas Phase and Its Modulation by Beta-Carotene and N-Acetylcysteine
Toxicol. Sci., March 1, 2005; 84(1): 81 - 87.
[Abstract] [Full Text] [PDF]


Home page
Arch Otolaryngol Head Neck SurgHome page
C. F. Perry, M. Stevens, I. Rabie, M.-E. Yarker, J. Cochrane, E. Perry, R. Traficante, and W. Coman
Chemoprevention of Head and Neck Cancer With Retinoids: A Negative Result
Arch Otolaryngol Head Neck Surg, March 1, 2005; 131(3): 198 - 203.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
J.-L. Lefebvre
Current clinical outcomes demand new treatment options for SCCHN
Ann. Onc., January 1, 2005; 16(suppl_6): vi7 - vi12.
[Abstract] [Full Text] [PDF]


Home page
Clin Med ResHome page
J. Sudbo
Novel Management of Oral Cancer: A Paradigm of Predictive Oncology
Clin. Med. Res., November 1, 2004; 2(4): 233 - 242.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
F. R. Khuri and R. Lotan
Retinoids in Lung Cancer: Friend, Foe, or Fellow Traveler?
J. Clin. Oncol., September 1, 2004; 22(17): 3435 - 3437.
[Full Text] [PDF]


Home page
JCOHome page
J. S. Kim, H. Lee, H. Kim, Y. M. Shim, J. Han, J. Park, and D.-H. Kim
Promoter Methylation of Retinoic Acid Receptor Beta 2 and the Development of Second Primary Lung Cancers in Non-Small-Cell Lung Cancer
J. Clin. Oncol., September 1, 2004; 22(17): 3443 - 3450.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
R. L. Keith, Y. E. Miller, T. M. Hudish, C. E. Girod, S. Sotto-Santiago, W. A. Franklin, R. A. Nemenoff, T. H. March, S. P. Nana-Sinkam, and M. W. Geraci
Pulmonary Prostacyclin Synthase Overexpression Chemoprevents Tobacco Smoke Lung Carcinogenesis in Mice
Cancer Res., August 15, 2004; 64(16): 5897 - 5904.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
F. R. Khuri and V. Cohen
Molecularly Targeted Approaches to the Chemoprevention of Lung Cancer
Clin. Cancer Res., June 15, 2004; 10(12): 4249S - 4253S.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
J. C. Rhee, F. R. Khuri, and D. M. Shin
Advances in Chemoprevention of Head and Neck Cancer
Oncologist, June 1, 2004; 9(3): 302 - 311.
[Abstract] [Full Text] [PDF]


Home page
CA Cancer J ClinHome page
A. S. Tsao, E. S. Kim, and W. K. Hong
Chemoprevention of Cancer
CA Cancer J Clin, May 1, 2004; 54(3): 150 - 180.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
R. C. Winterhalder, F. R. Hirsch, G. K. Kotantoulas, W. A. Franklin, and P. A. Bunn Jr
Chemoprevention of lung cancer--from biology to clinical reality
Ann. Onc., February 1, 2004; 15(2): 185 - 196.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
D. G. Pfister, D. H. Johnson, C. G. Azzoli, W. Sause, T. J. Smith, S. Baker Jr, J. Olak, D. Stover, J. R. Strawn, A. T. Turrisi, et al.
American Society of Clinical Oncology Treatment of Unresectable Non-Small-Cell Lung Cancer Guideline: Update 2003
J. Clin. Oncol., January 15, 2004; 22(2): 330 - 353.
[Full Text] [PDF]


Home page
JCOHome page
C. M. Rudin, E. E.W. Cohen, V. A. Papadimitrakopoulou, S. Silverman Jr, W. Recant, A. K. El-Naggar, K. Stenson, S. M. Lippman, W. K. Hong, and E. E. Vokes
An Attenuated Adenovirus, ONYX-015, As Mouthwash Therapy for Premalignant Oral Dysplasia
J. Clin. Oncol., December 15, 2003; 21(24): 4546 - 4552.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
A. M Myhre, M. H Carlsen, S. K Bohn, H. L Wold, P. Laake, and R. Blomhoff
Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations
Am. J. Clinical Nutrition, December 1, 2003; 78(6): 1152 - 1159.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. Means-Markwell, R. I. Linnoila, J. Williams, P. A. Janne, F. Kaye, K. O'Neil, and B. E. Johnson
Prospective Study of the Airways and Pulmonary Parenchyma of Patients at Risk for a Second Lung Cancer
Clin. Cancer Res., December 1, 2003; 9(16): 5915 - 5921.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
S. M. Zhang, W. C. Willett, J. Selhub, J. E. Manson, G. A. Colditz, and S. E. Hankinson
A Prospective Study of Plasma Total Cysteine and Risk of Breast Cancer
Cancer Epidemiol. Biomarkers Prev., November 1, 2003; 12(11): 1188 - 1193.
[Abstract] [Full Text]


Home page
Ann. Thorac. Surg.Home page
D. Rice, H.-W. Kim, A. Sabichi, S. Lippman, J. J. Lee, B. Williams, A. Vaporciyan, W. R. Smythe, S. Swisher, G. Walsh, et al.
The risk of second primary tumors after resection of Stage I nonsmall cell lung cancer
Ann. Thorac. Surg., October 1, 2003; 76(4): 1001 - 1008.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
K.-H. Chun, J. W. Kosmeder II, S. Sun, J. M. Pezzuto, R. Lotan, W. K. Hong, and H.-Y. Lee
Effects of Deguelin on the Phosphatidylinositol 3-Kinase/Akt Pathway and Apoptosis in Premalignant Human Bronchial Epithelial Cells
J Natl Cancer Inst, February 19, 2003; 95(4): 291 - 302.
[Abstract] [Full Text] [PDF]


Home page
Toxicol PatholHome page
A. Nyska, A. Suttie, S. Bakshi, L. Lomnitski, S. Grossman, M. Bergman, V. Ben-Shaul, P. Crocket, J. K. Haseman, G. Moser, et al.
Slowing Tumorigenic Progression in TRAMP Mice and Prostatic Carcinoma Cell Lines Using Natural Anti-Oxidant from Spinach, NAO--A Comparative Study of Three Anti-Oxidants
Toxicol Pathol, January 1, 2003; 31(1): 39 - 51.
[Abstract] [PDF]


Home page
ThoraxHome page
G E Goodman
Lung cancer * 1: Prevention of lung cancer
Thorax, November 1, 2002; 57(11): 994 - 999.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
S. S. Hecht, P. Upadhyaya, M. Wang, R. L. Bliss, E. J. McIntee, and P. M.J. Kenney
Inhibition of lung tumorigenesis in A/J mice by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine and myo-inositol, individually and in combination
Carcinogenesis, September 1, 2002; 23(9): 1455 - 1461.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
H. Witschi, I. Espiritu, S. T. Dance, and M. S. Miller
A Mouse Lung Tumor Model of Tobacco Smoke Carcinogenesis
Toxicol. Sci., August 1, 2002; 68(2): 322 - 330.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
C. Monnerat, S. Faivre, S. Temam, J. Bourhis, and E. Raymond
End points for new agents in induction chemotherapy for locally advanced head and neck cancers
Ann. Onc., July 1, 2002; 13(7): 995 - 1006.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
D. C. Malins, K. E. Hellstrom, K. M. Anderson, P. M. Johnson, and M. A. Vinson
Antioxidant-induced changes in oxidized DNA
PNAS, April 18, 2002; (2002) 82111199.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
F. J. Van Schooten, A. Besarati Nia, S. De Flora, F. D'Agostini, A. Izzotti, A. Camoirano, A. J. M. Balm, J. W. Dallinga, A. Bast, G. R. M. M. Haenen, et al.
Effects of Oral Administration of N-Acetyl-L-cysteine: A Multi-Biomarker Study in Smokers
Cancer Epidemiol. Biomarkers Prev., February 1, 2002; 11(2): 167 - 175.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
H. Witschi, I. Espiritu, M. Suffia, and K. E. Pinkerton
Expression of cyclin D1/2 in the lungs of strain A/J mice fed chemopreventive agents
Carcinogenesis, February 1, 2002; 23(2): 289 - 294.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
S. M. Lippman and M. R. Spitz
Lung Cancer Chemoprevention: An Integrated Approach
J. Clin. Oncol., September 15, 2001; 19(90001): 74s - 82.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
U. Pastorino
Molecular Targeting: the New Challenge in Lung Cancer Prevention
J Natl Cancer Inst, August 15, 2001; 93(16): 1190 - 1191.
[Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
F. R. Khuri, E. S. Kim, J. J. Lee, R. J. Winn, S. E. Benner, S. M. Lippman, K. K. Fu, J. S. Cooper, E. E. Vokes, R. M. Chamberlain, et al.
The Impact of Smoking Status, Disease Stage, and Index Tumor Site on Second Primary Tumor Incidence and Tumor Recurrence in the Head and Neck Retinoid Chemoprevention Trial
Cancer Epidemiol. Biomarkers Prev., August 1, 2001; 10(8): 823 - 829.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
E. Szabo
Lung Epithelial Proliferation: a Biomarker for Chemoprevention Trials?
J Natl Cancer Inst, July 18, 2001; 93(14): 1042 - 1043.
[Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
J. J. Lee, D. Liu, J. S. Lee, J. M. Kurie, F. R. Khuri, H. Ibarguen, R. C. Morice, G. Walsh, J. Y. Ro, A. Broxson, et al.
Long-Term Impact of Smoking on Lung Epithelial Proliferation in Current and Former Smokers
J Natl Cancer Inst, July 18, 2001; 93(14): 1081 - 1088.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
S. De Flora, A. Izzotti, F. D'Agostini, and R. M. Balansky
Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points
Carcinogenesis, July 1, 2001; 22(7): 999 - 1013.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
D. M. Shin, F. R. Khuri, B. Murphy, A. S. Garden, G. Clayman, M. Francisco, D. Liu, B. S. Glisson, L. Ginsberg, V. Papadimitrakopoulou, et al.
Combined Interferon-Alfa, 13-cis-Retinoic Acid, and Alpha-Tocopherol in Locally Advanced Head and Neck Squamous Cell Carcinoma: Novel Bioadjuvant Phase II Trial
J. Clin. Oncol., June 15, 2001; 19(12): 3010 - 3017.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
S. M. Lippman, J. J. Lee, D. D. Karp, E. E. Vokes, S. E. Benner, G. E. Goodman, F. R. Khuri, R. Marks, R. J. Winn, W. Fry, et al.
Randomized Phase III Intergroup Trial of Isotretinoin to Prevent Second Primary Tumors in Stage I Non-Small-Cell Lung Cancer
J Natl Cancer Inst, April 18, 2001; 93(8): 605 - 618.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
F. R. Khuri, J. S. Lee, S. M. Lippman, J. J. Lee, S. Kalapurakal, R. Yu, J. Y. Ro, R. C. Morice, W. K. Hong, and W. N. Hittelman
Modulation of Proliferating Cell Nuclear Antigen in the Bronchial Epithelium of Smokers
Cancer Epidemiol. Biomarkers Prev., April 1, 2001; 10(4): 311 - 318.
[Abstract] [Full Text]


Home page
Cancer Res.Home page
S. T. Mayne, B. Cartmel, M. Baum, G. Shor-Posner, B. G. Fallon, K. Briskin, J. Bean, T. Zheng, D. Cooper, C. Friedman, et al.
Randomized Trial of Supplemental {beta}-Carotene to Prevent Second Head and Neck Cancer
Cancer Res., February 1, 2001; 61(4): 1457 - 1463.
[Abstract] [Full Text]


Home page
JNCI J Natl Cancer InstHome page
G. S. Omenn
Chemoprevention of Lung Cancer Is Proving Difficult and Frustrating, Requiring New Approaches
J Natl Cancer Inst, June 21, 2000; 92(12): 959 - 960.
[Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
D. C. Malins, K. E. Hellstrom, K. M. Anderson, P. M. Johnson, and M. A. Vinson
Antioxidant-induced changes in oxidized DNA
PNAS, April 30, 2002; 99(9): 5937 - 5941.
[Abstract] [Full Text] [PDF]



Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.