Randomized phase II-III trial of combination beta and gamma interferons and etoposide and cisplatin in inoperable non-small cell cancer of the lung

Joan H. Schiller, Barry Storer, Robert Dreicer, Debra Rosenquist, Michael Frontiera, Paul P. Carbone

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Abstract

We observed major responses in two patients with adenocarcinoma of the lung who had received a combination of interferon (IFN)-β and IFN-γ, immediately followed by chemotherapy. To verify these observations, we initiated a prospective randomized phase II-III trial of etoposide and cisplatin, with or without IFN-β and IFN-γ, in patients with inoperable non-small cell lung cancer. Thirty-seven patients were randomized to receive either two cycles of chemotherapy or 6 weeks of IFN-β plus IFN-γ followed by two cycles of chemotherapy. Chemotherapy consisted of 60 mg of cisplation/m2 on day 1 and 120 mg of etoposide/m2 on days 4, 6, and 8, repeated every 21 days. Patients who were randomized to the IFN plus chemotherapy arm received 200 μg of IFN-γ and 30 × 106 U of IFN-β three times per week for 6 weeks, followed by two cycles of chemotherapy. Three of 18 (17%) eligible patients in the chemotherapy arm and two of 18 (11%) patients in the combination arm had partial responses. All responses occurred while patients were receiving chemotherapy. Median survival was 190 days for the chemotherapy arm and 246 days in the combined modality arm, as estimated from Kaplan-Meier curves (P = .35). We observed no significant difference in subjective toxic effects between the two arms. We observed more hematologic toxicity during chemotherapy on the combined modality arm (P = .02). We conclude that pretreatment with IFN-β and IFN-γ does not enhance the efficacy of etoposide and cisplatin in this disease. Although the combined modality arm is relatively well tolerated, it does result in more chemotherapy-associated toxic effects. This study also exemplifies a hybrid phase II-III trial design, which is useful in allowing phase II results to be quickly incorporated into a phase III trial. [J Natl Cancer Inst 81:1739-1743, 1989]

Original languageEnglish (US)
Pages (from-to)1739-1743
Number of pages5
JournalJournal of the National Cancer Institute
Volume81
Issue number22
DOIs
StatePublished - Nov 15 1989

Fingerprint

Interferon-γ
Interferons
Cisplatin
Chemotherapy
Interferon-beta
Etoposide
Lung
Non-Small Cell Lung Carcinoma
Interferon-gamma
Cancer
Drug Therapy
Cell
Modality
Poisons
Cycle
Kaplan-Meier
Lung Cancer
Toxicity
Immediately
Efficacy

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging
  • Oncology
  • Cancer Research

Cite this

Randomized phase II-III trial of combination beta and gamma interferons and etoposide and cisplatin in inoperable non-small cell cancer of the lung. / Schiller, Joan H.; Storer, Barry; Dreicer, Robert; Rosenquist, Debra; Frontiera, Michael; Carbone, Paul P.

In: Journal of the National Cancer Institute, Vol. 81, No. 22, 15.11.1989, p. 1739-1743.

Research output: Contribution to journalArticle

Schiller, Joan H. ; Storer, Barry ; Dreicer, Robert ; Rosenquist, Debra ; Frontiera, Michael ; Carbone, Paul P. / Randomized phase II-III trial of combination beta and gamma interferons and etoposide and cisplatin in inoperable non-small cell cancer of the lung. In: Journal of the National Cancer Institute. 1989 ; Vol. 81, No. 22. pp. 1739-1743.
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AB - We observed major responses in two patients with adenocarcinoma of the lung who had received a combination of interferon (IFN)-β and IFN-γ, immediately followed by chemotherapy. To verify these observations, we initiated a prospective randomized phase II-III trial of etoposide and cisplatin, with or without IFN-β and IFN-γ, in patients with inoperable non-small cell lung cancer. Thirty-seven patients were randomized to receive either two cycles of chemotherapy or 6 weeks of IFN-β plus IFN-γ followed by two cycles of chemotherapy. Chemotherapy consisted of 60 mg of cisplation/m2 on day 1 and 120 mg of etoposide/m2 on days 4, 6, and 8, repeated every 21 days. Patients who were randomized to the IFN plus chemotherapy arm received 200 μg of IFN-γ and 30 × 106 U of IFN-β three times per week for 6 weeks, followed by two cycles of chemotherapy. Three of 18 (17%) eligible patients in the chemotherapy arm and two of 18 (11%) patients in the combination arm had partial responses. All responses occurred while patients were receiving chemotherapy. Median survival was 190 days for the chemotherapy arm and 246 days in the combined modality arm, as estimated from Kaplan-Meier curves (P = .35). We observed no significant difference in subjective toxic effects between the two arms. We observed more hematologic toxicity during chemotherapy on the combined modality arm (P = .02). We conclude that pretreatment with IFN-β and IFN-γ does not enhance the efficacy of etoposide and cisplatin in this disease. Although the combined modality arm is relatively well tolerated, it does result in more chemotherapy-associated toxic effects. This study also exemplifies a hybrid phase II-III trial design, which is useful in allowing phase II results to be quickly incorporated into a phase III trial. [J Natl Cancer Inst 81:1739-1743, 1989]

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