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Superiority of Alternating Non-Cross-Resistant Chemotherapy in Extensive Small Cell Lung Cancer: A Multicenter, Randomized Clinical Trial by the National Cancer Institute of Canada

W. K. EVANS, M.D.; R. FELD, M.D.; N. MURRAY, M.D.; A. WILLAN, Ph.D., M.D.; D. OSOBA, M.D.; F. A. SHEPHERD, M.D.; D. A. CLARK, M.D., Ph.D.; M. LEVITT, M.Sc., M.D.; A. MacDONALD, M.D.; K. WILSON, M.B.; W. SHELLEY, M.D.; and J. PATER, M.Sc
[+] Article and Author Information

Grant support: The National Cancer Institute of Canada.

▸Requests for reprints should be addressed to W. K. Evans, M.D.; Ottawa Regional Cancer Centre, 190 Melrose Ave., Ottawa, Ontario, Canada K1Y 4K7.


Kingston, Ontario, Canada


Ann Intern Med. 1987;107(4):451-458. doi:10.7326/0003-4819-107-4-451
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The National Cancer Institute of Canada Clinical Trials Group conducted a prospective randomized study comparing standard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer. "Standard" treatment consisted of cyclophosphamide (1000 mg/m2 body surface area); doxorubicin (50 mg/m2), and vincristine (2 mg) every 3 weeks for six courses. Alternating chemotherapy was cyclophosphamide, doxorubicin, and vincristine alternating with etoposide (100 mg/m2 on days 1 to 3) and cisplatin (25 mg/m2 on days 1 to 3) every 3 weeks for six treatment cycles. Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival. Best response was higher in patients on alternating chemotherapy (complete plus partial response, 80% compared with 63.2%p < 0.002). Progression-free survival for patients on alternating chemotherapy was superior (p < 0.0001) as was overall survival (p = 0.03). Major toxicities were equally frequent in both treatment groups. These results show a modest superiority of alternating chemotherapy over standard therapy in extensive small cell lung cancer.

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