A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer

A preliminary report from the Okayama Lung Cancer Study Group

Y. Segawa, H. Ueoka, Katsuyuki Kiura, H. Kamei, Masahiro Tabata, K. Sakae, Y. Hiraki, S. Kawahara, K. Eguchi, S. Hiraki, M. Harada

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status ≤ 2, age ≤ 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m-2, days 1-5) and 5-fluorouracil (5-FU) (500 mg m-2, days 1-5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily with a 6-h interfraction interval; total radiation dose, 62.5-70 Gy). Of the 50 patients entered, 37 (74%) responded to this chemoradiotherapy, including two (4%) with complete response. By a median follow-up time of 41.0 months, 35 patients had died and 15 were still alive. The median time to progression for responding patients was 14.1 months (range, 2.6-51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0% at 1 year, 46.0% at 2 years and 27.6% at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for NO-2 disease (n = 37) vs 10.7 months for N3 disease (n = 13); P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (≥ Grade 3, 58% and 60% respectively). Other toxicities of ≥ Grade 3 included thrombocytopenia (26%), anaemia (26%), nausea/vomiting (16%) and radiation oesophagitis (6%). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC.

Original languageEnglish
Pages (from-to)104-111
Number of pages8
JournalBritish Journal of Cancer
Volume82
Issue number1
Publication statusPublished - 2000

Fingerprint

Non-Small Cell Lung Carcinoma
Fluorouracil
Cisplatin
Lung Neoplasms
Thorax
Radiation
Chemoradiotherapy
Survival
Radiation Dosage
Esophagitis
Leukopenia
Drug Combinations
Therapeutics
Neutropenia
Platinum
Nausea
Vomiting
Meta-Analysis
Anemia
Survival Rate

Keywords

  • 5-Fluorouracil
  • Cisplatin
  • Combined chemoradiotherapy
  • Hyperfractionated thoracic radiation
  • Non-small-cell lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer : A preliminary report from the Okayama Lung Cancer Study Group. / Segawa, Y.; Ueoka, H.; Kiura, Katsuyuki; Kamei, H.; Tabata, Masahiro; Sakae, K.; Hiraki, Y.; Kawahara, S.; Eguchi, K.; Hiraki, S.; Harada, M.

In: British Journal of Cancer, Vol. 82, No. 1, 2000, p. 104-111.

Research output: Contribution to journalArticle

@article{319378fa741c40f4a27c61fe115dec74,
title = "A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer: A preliminary report from the Okayama Lung Cancer Study Group",
abstract = "A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status ≤ 2, age ≤ 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m-2, days 1-5) and 5-fluorouracil (5-FU) (500 mg m-2, days 1-5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily with a 6-h interfraction interval; total radiation dose, 62.5-70 Gy). Of the 50 patients entered, 37 (74{\%}) responded to this chemoradiotherapy, including two (4{\%}) with complete response. By a median follow-up time of 41.0 months, 35 patients had died and 15 were still alive. The median time to progression for responding patients was 14.1 months (range, 2.6-51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0{\%} at 1 year, 46.0{\%} at 2 years and 27.6{\%} at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for NO-2 disease (n = 37) vs 10.7 months for N3 disease (n = 13); P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (≥ Grade 3, 58{\%} and 60{\%} respectively). Other toxicities of ≥ Grade 3 included thrombocytopenia (26{\%}), anaemia (26{\%}), nausea/vomiting (16{\%}) and radiation oesophagitis (6{\%}). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC.",
keywords = "5-Fluorouracil, Cisplatin, Combined chemoradiotherapy, Hyperfractionated thoracic radiation, Non-small-cell lung cancer",
author = "Y. Segawa and H. Ueoka and Katsuyuki Kiura and H. Kamei and Masahiro Tabata and K. Sakae and Y. Hiraki and S. Kawahara and K. Eguchi and S. Hiraki and M. Harada",
year = "2000",
language = "English",
volume = "82",
pages = "104--111",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer

T2 - A preliminary report from the Okayama Lung Cancer Study Group

AU - Segawa, Y.

AU - Ueoka, H.

AU - Kiura, Katsuyuki

AU - Kamei, H.

AU - Tabata, Masahiro

AU - Sakae, K.

AU - Hiraki, Y.

AU - Kawahara, S.

AU - Eguchi, K.

AU - Hiraki, S.

AU - Harada, M.

PY - 2000

Y1 - 2000

N2 - A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status ≤ 2, age ≤ 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m-2, days 1-5) and 5-fluorouracil (5-FU) (500 mg m-2, days 1-5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily with a 6-h interfraction interval; total radiation dose, 62.5-70 Gy). Of the 50 patients entered, 37 (74%) responded to this chemoradiotherapy, including two (4%) with complete response. By a median follow-up time of 41.0 months, 35 patients had died and 15 were still alive. The median time to progression for responding patients was 14.1 months (range, 2.6-51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0% at 1 year, 46.0% at 2 years and 27.6% at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for NO-2 disease (n = 37) vs 10.7 months for N3 disease (n = 13); P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (≥ Grade 3, 58% and 60% respectively). Other toxicities of ≥ Grade 3 included thrombocytopenia (26%), anaemia (26%), nausea/vomiting (16%) and radiation oesophagitis (6%). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC.

AB - A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status ≤ 2, age ≤ 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m-2, days 1-5) and 5-fluorouracil (5-FU) (500 mg m-2, days 1-5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily with a 6-h interfraction interval; total radiation dose, 62.5-70 Gy). Of the 50 patients entered, 37 (74%) responded to this chemoradiotherapy, including two (4%) with complete response. By a median follow-up time of 41.0 months, 35 patients had died and 15 were still alive. The median time to progression for responding patients was 14.1 months (range, 2.6-51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0% at 1 year, 46.0% at 2 years and 27.6% at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for NO-2 disease (n = 37) vs 10.7 months for N3 disease (n = 13); P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (≥ Grade 3, 58% and 60% respectively). Other toxicities of ≥ Grade 3 included thrombocytopenia (26%), anaemia (26%), nausea/vomiting (16%) and radiation oesophagitis (6%). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC.

KW - 5-Fluorouracil

KW - Cisplatin

KW - Combined chemoradiotherapy

KW - Hyperfractionated thoracic radiation

KW - Non-small-cell lung cancer

UR - http://www.scopus.com/inward/record.url?scp=0033989705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033989705&partnerID=8YFLogxK

M3 - Article

VL - 82

SP - 104

EP - 111

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 1

ER -