Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer

Russell F. DeVore, David H. Johnson, Jeffrey Crawford, Jennifer Garst, Isaiah W. Dimery, John Eckardt, S. Gail Eckhardt, Gary L. Elfring, Larry J. Schaaf, Cristy K. Hanover, Langdon L. Miller

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Abstract

Purpose: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small- cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. Patients and Methods: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m2) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m2) after CPT-11 administration on day 1. Results: Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1- year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32.7%) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to ≤ 40 mg/m2 in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. Conclusion: CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.

Original languageEnglish (US)
Pages (from-to)2710-2720
Number of pages11
JournalJournal of Clinical Oncology
Volume17
Issue number9
StatePublished - Sep 1999

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irinotecan
Non-Small Cell Lung Carcinoma
Cisplatin
Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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DeVore, R. F., Johnson, D. H., Crawford, J., Garst, J., Dimery, I. W., Eckardt, J., ... Miller, L. L. (1999). Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer. Journal of Clinical Oncology, 17(9), 2710-2720.

Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer. / DeVore, Russell F.; Johnson, David H.; Crawford, Jeffrey; Garst, Jennifer; Dimery, Isaiah W.; Eckardt, John; Eckhardt, S. Gail; Elfring, Gary L.; Schaaf, Larry J.; Hanover, Cristy K.; Miller, Langdon L.

In: Journal of Clinical Oncology, Vol. 17, No. 9, 09.1999, p. 2710-2720.

Research output: Contribution to journalArticle

DeVore, RF, Johnson, DH, Crawford, J, Garst, J, Dimery, IW, Eckardt, J, Eckhardt, SG, Elfring, GL, Schaaf, LJ, Hanover, CK & Miller, LL 1999, 'Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer', Journal of Clinical Oncology, vol. 17, no. 9, pp. 2710-2720.
DeVore, Russell F. ; Johnson, David H. ; Crawford, Jeffrey ; Garst, Jennifer ; Dimery, Isaiah W. ; Eckardt, John ; Eckhardt, S. Gail ; Elfring, Gary L. ; Schaaf, Larry J. ; Hanover, Cristy K. ; Miller, Langdon L. / Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer. In: Journal of Clinical Oncology. 1999 ; Vol. 17, No. 9. pp. 2710-2720.
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abstract = "Purpose: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small- cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. Patients and Methods: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m2) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m2) after CPT-11 administration on day 1. Results: Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8{\%} of patients (15 of 52; 95{\%} confidence interval, 16.5{\%} to 41.2{\%}). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1- year survival rate was 37{\%}. Grade 3/4 adverse events consisted primarily of nausea (32.7{\%}) or vomiting (13.5{\%}), late-onset diarrhea (17.3{\%}), and neutropenia (46.1{\%}). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to ≤ 40 mg/m2 in the majority of patients (31 of 52; 60{\%}), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. Conclusion: CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.",
author = "DeVore, {Russell F.} and Johnson, {David H.} and Jeffrey Crawford and Jennifer Garst and Dimery, {Isaiah W.} and John Eckardt and Eckhardt, {S. Gail} and Elfring, {Gary L.} and Schaaf, {Larry J.} and Hanover, {Cristy K.} and Miller, {Langdon L.}",
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T1 - Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer

AU - DeVore, Russell F.

AU - Johnson, David H.

AU - Crawford, Jeffrey

AU - Garst, Jennifer

AU - Dimery, Isaiah W.

AU - Eckardt, John

AU - Eckhardt, S. Gail

AU - Elfring, Gary L.

AU - Schaaf, Larry J.

AU - Hanover, Cristy K.

AU - Miller, Langdon L.

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N2 - Purpose: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small- cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. Patients and Methods: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m2) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m2) after CPT-11 administration on day 1. Results: Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1- year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32.7%) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to ≤ 40 mg/m2 in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. Conclusion: CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.

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