Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer

A report of high response rates and prolonged survival

J. H. Schiller, B. Storer, J. Berlin, J. Wittenkeller, M. Larson, L. Pharo, M. Larson, W. Berry

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Purpose: Based on preclinical and clinical studies that suggested amifostine may potentiate the effects of cytotoxic drugs, we conducted a phase II trial of amifostine, cisplatin, and vinblastine (ACV) in patients with metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-five patients with metastatic NSCLC received amifostine (740 or 910 mg/m2) before 120 mg/m2 of cisplatin on day 1, plus weekly 5 mg/m2 of vinblastine without amifostine. Cycles were repeated every 4 weeks. Patients were required to have good performance status, no prior chemotherapy or biologic therapy, adequate organ function, and measurable disease. Results: Sixteen of 25 assessable patients had an objective response documented by computed tomographic (CT) scan (64%; 95% confidence interval, 45% to 85%). With a median duration of follow-up of 19.2 months, the estimated median survival is 17 months and 1-year survival is 64% (± 10%). Toxicities included grades 3 and 4 neutropenia (8% and 92%, respectively) and nausea and vomiting (32% and 4%, respectively). Reversible grade 3 nephrotoxicity occurred in 12% of patients, although only one of 13 patients (7%) who received ≥ four cycles of therapy had ≥ 40% reduction in creatinine clearance. Grade 3 neuropathy was observed in seven patients at cumulative cisplatin doses that ranged from 324 to 660 mg/m2; grade 3 ototoxicity occurred in three patients at cumulative cisplatin doses that ranged from 390 to 450 mg/m2. Four patients (16%) required early stopping of an amifostine infusion due to hypotension. Conclusion: ACV appears to be a highly active regimen in metastatic NSCLC. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative doses of cisplatin. Although the sample size of this trial is small, the results are significantly encouraging to warrant confirmation in randomized multiinstitutional trials.

Original languageEnglish (US)
Pages (from-to)1913-1921
Number of pages9
JournalJournal of Clinical Oncology
Volume14
Issue number6
StatePublished - Jun 1996

Fingerprint

Amifostine
Vinblastine
Non-Small Cell Lung Carcinoma
Cisplatin
Survival Rate
Biological Therapy
Survival
Neutropenia
Sample Size
Hypotension
Nausea
Vomiting
Renal Insufficiency
Creatinine
Confidence Intervals

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schiller, J. H., Storer, B., Berlin, J., Wittenkeller, J., Larson, M., Pharo, L., ... Berry, W. (1996). Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer: A report of high response rates and prolonged survival. Journal of Clinical Oncology, 14(6), 1913-1921.

Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer : A report of high response rates and prolonged survival. / Schiller, J. H.; Storer, B.; Berlin, J.; Wittenkeller, J.; Larson, M.; Pharo, L.; Larson, M.; Berry, W.

In: Journal of Clinical Oncology, Vol. 14, No. 6, 06.1996, p. 1913-1921.

Research output: Contribution to journalArticle

Schiller, JH, Storer, B, Berlin, J, Wittenkeller, J, Larson, M, Pharo, L, Larson, M & Berry, W 1996, 'Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer: A report of high response rates and prolonged survival', Journal of Clinical Oncology, vol. 14, no. 6, pp. 1913-1921.
Schiller, J. H. ; Storer, B. ; Berlin, J. ; Wittenkeller, J. ; Larson, M. ; Pharo, L. ; Larson, M. ; Berry, W. / Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer : A report of high response rates and prolonged survival. In: Journal of Clinical Oncology. 1996 ; Vol. 14, No. 6. pp. 1913-1921.
@article{242ad9e097994015aa35645e66a51b1d,
title = "Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer: A report of high response rates and prolonged survival",
abstract = "Purpose: Based on preclinical and clinical studies that suggested amifostine may potentiate the effects of cytotoxic drugs, we conducted a phase II trial of amifostine, cisplatin, and vinblastine (ACV) in patients with metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-five patients with metastatic NSCLC received amifostine (740 or 910 mg/m2) before 120 mg/m2 of cisplatin on day 1, plus weekly 5 mg/m2 of vinblastine without amifostine. Cycles were repeated every 4 weeks. Patients were required to have good performance status, no prior chemotherapy or biologic therapy, adequate organ function, and measurable disease. Results: Sixteen of 25 assessable patients had an objective response documented by computed tomographic (CT) scan (64{\%}; 95{\%} confidence interval, 45{\%} to 85{\%}). With a median duration of follow-up of 19.2 months, the estimated median survival is 17 months and 1-year survival is 64{\%} (± 10{\%}). Toxicities included grades 3 and 4 neutropenia (8{\%} and 92{\%}, respectively) and nausea and vomiting (32{\%} and 4{\%}, respectively). Reversible grade 3 nephrotoxicity occurred in 12{\%} of patients, although only one of 13 patients (7{\%}) who received ≥ four cycles of therapy had ≥ 40{\%} reduction in creatinine clearance. Grade 3 neuropathy was observed in seven patients at cumulative cisplatin doses that ranged from 324 to 660 mg/m2; grade 3 ototoxicity occurred in three patients at cumulative cisplatin doses that ranged from 390 to 450 mg/m2. Four patients (16{\%}) required early stopping of an amifostine infusion due to hypotension. Conclusion: ACV appears to be a highly active regimen in metastatic NSCLC. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative doses of cisplatin. Although the sample size of this trial is small, the results are significantly encouraging to warrant confirmation in randomized multiinstitutional trials.",
author = "Schiller, {J. H.} and B. Storer and J. Berlin and J. Wittenkeller and M. Larson and L. Pharo and M. Larson and W. Berry",
year = "1996",
month = "6",
language = "English (US)",
volume = "14",
pages = "1913--1921",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "6",

}

TY - JOUR

T1 - Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer

T2 - A report of high response rates and prolonged survival

AU - Schiller, J. H.

AU - Storer, B.

AU - Berlin, J.

AU - Wittenkeller, J.

AU - Larson, M.

AU - Pharo, L.

AU - Larson, M.

AU - Berry, W.

PY - 1996/6

Y1 - 1996/6

N2 - Purpose: Based on preclinical and clinical studies that suggested amifostine may potentiate the effects of cytotoxic drugs, we conducted a phase II trial of amifostine, cisplatin, and vinblastine (ACV) in patients with metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-five patients with metastatic NSCLC received amifostine (740 or 910 mg/m2) before 120 mg/m2 of cisplatin on day 1, plus weekly 5 mg/m2 of vinblastine without amifostine. Cycles were repeated every 4 weeks. Patients were required to have good performance status, no prior chemotherapy or biologic therapy, adequate organ function, and measurable disease. Results: Sixteen of 25 assessable patients had an objective response documented by computed tomographic (CT) scan (64%; 95% confidence interval, 45% to 85%). With a median duration of follow-up of 19.2 months, the estimated median survival is 17 months and 1-year survival is 64% (± 10%). Toxicities included grades 3 and 4 neutropenia (8% and 92%, respectively) and nausea and vomiting (32% and 4%, respectively). Reversible grade 3 nephrotoxicity occurred in 12% of patients, although only one of 13 patients (7%) who received ≥ four cycles of therapy had ≥ 40% reduction in creatinine clearance. Grade 3 neuropathy was observed in seven patients at cumulative cisplatin doses that ranged from 324 to 660 mg/m2; grade 3 ototoxicity occurred in three patients at cumulative cisplatin doses that ranged from 390 to 450 mg/m2. Four patients (16%) required early stopping of an amifostine infusion due to hypotension. Conclusion: ACV appears to be a highly active regimen in metastatic NSCLC. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative doses of cisplatin. Although the sample size of this trial is small, the results are significantly encouraging to warrant confirmation in randomized multiinstitutional trials.

AB - Purpose: Based on preclinical and clinical studies that suggested amifostine may potentiate the effects of cytotoxic drugs, we conducted a phase II trial of amifostine, cisplatin, and vinblastine (ACV) in patients with metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-five patients with metastatic NSCLC received amifostine (740 or 910 mg/m2) before 120 mg/m2 of cisplatin on day 1, plus weekly 5 mg/m2 of vinblastine without amifostine. Cycles were repeated every 4 weeks. Patients were required to have good performance status, no prior chemotherapy or biologic therapy, adequate organ function, and measurable disease. Results: Sixteen of 25 assessable patients had an objective response documented by computed tomographic (CT) scan (64%; 95% confidence interval, 45% to 85%). With a median duration of follow-up of 19.2 months, the estimated median survival is 17 months and 1-year survival is 64% (± 10%). Toxicities included grades 3 and 4 neutropenia (8% and 92%, respectively) and nausea and vomiting (32% and 4%, respectively). Reversible grade 3 nephrotoxicity occurred in 12% of patients, although only one of 13 patients (7%) who received ≥ four cycles of therapy had ≥ 40% reduction in creatinine clearance. Grade 3 neuropathy was observed in seven patients at cumulative cisplatin doses that ranged from 324 to 660 mg/m2; grade 3 ototoxicity occurred in three patients at cumulative cisplatin doses that ranged from 390 to 450 mg/m2. Four patients (16%) required early stopping of an amifostine infusion due to hypotension. Conclusion: ACV appears to be a highly active regimen in metastatic NSCLC. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative doses of cisplatin. Although the sample size of this trial is small, the results are significantly encouraging to warrant confirmation in randomized multiinstitutional trials.

UR - http://www.scopus.com/inward/record.url?scp=0030013080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030013080&partnerID=8YFLogxK

M3 - Article

VL - 14

SP - 1913

EP - 1921

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 6

ER -