Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer

Daniel C. Ihde, James L. Mulshine, Barnett S. Kramer, Seth M. Steinberg, R. Ilona Linnoila, Adi F. Gazdar, Margaret Edison, Ruby M. Phelps, May Lesar, John C. Phares, Jane Grayson, John D. Minna, Bruce E. Johnson

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

Purpose: We performed a prospective randomized clinical trial to determine whether higher doses of etoposide and cisplatin (EP) yield more complete responses or longer survival in small-cell lung cancer (SCLC) patients. Patients and Methods: Ninety patients with previously untreated extensive- stage SCLC fulfilled criteria for randomization to standard-dose versus high- dose EP. Another 25 patients at risk of excessive toxicity from high-dose treatment were given standard-dose therapy. During cycles 1 and 2 of EP, patients on standard-dose treatment received intravenous etoposide 80 mg/m2 on days 1 to 3 and cisplatin 80 mg/m2 on day 1 every 3 weeks; high-dose treatment consisted of etoposide 80 mg/m2 on days 1 to 5 and cisplatin 27 mg/m2 on days 1 to 5 every 3 weeks. All patients received standard-dose EP in cycles 3 and 4. In cycles 5 through 8, completely responding patients continued standard-dose EP; all other patients received either cyclophosphamide, doxorubicin, and vincristine, or (if possible) a combination drug program based on in vitro drug sensitivity testing of tumor- cell lines established from individual patients. Results: Despite 68% higher doses and a 46% higher dose-rate intensity actually given to patients randomized to receive high-dose relative to those randomized to receive standard-dose EP, complete response rates (23% v 22%; P = .99) and median survival durations (10.7 and 11.4 months, respectively; P = .68) were virtually identical. Complete responses occurred in 4% of patients and the median survival duration was 5.8 months in nonrandomized patients. Leukopenia (P < .0001), thrombocytopenia (P < .0001), febrile neutropenia (P = .01), and weight loss (P = .02) were significantly more common in patients randomized to receive high-dose compared with standard-dose EP. Conclusion: No therapeutic benefits resulted from increasing planned doses by 67% for the first two cycles of EP in patients with extensive-stage SCLC. Higher doses were associated with substantially worse toxicities.

Original languageEnglish (US)
Pages (from-to)2022-2034
Number of pages13
JournalJournal of Clinical Oncology
Volume12
Issue number10
Publication statusPublished - Oct 1994

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ihde, D. C., Mulshine, J. L., Kramer, B. S., Steinberg, S. M., Linnoila, R. I., Gazdar, A. F., ... Johnson, B. E. (1994). Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. Journal of Clinical Oncology, 12(10), 2022-2034.