A randomized study comparing two different schedules of administration of cisplatin in combination with gemcitabine in advanced nonsmall cell lung carcinoma

Sergio Ricci, Andrea Antonuzzo, Luca Galli, Carmelo Tibaldi, Maurizio Bertuccelli, Andrea Lopes Pegna, Stefano Petruzzelli, Vittorio Bonifazi, Cinzia Orlandini, Pier Franco Conte

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Abstract

BACKGROUND: This randomized trial was designed to investigate the feasibility, toxicity, and activity of two different schedules of gemcitabine plus cisplatin in previously untreated patients with advanced (International Union Against Cancer (UICC) Stage IIIB-IV) nonsmall cell lung carcinoma (NSCLC). METHODS: From February 1997 to September 1998, 82 patients with advanced NSCLC were entered onto the study and were randomized to gemcitabine 1000 mg/m2 on Days 1, 8, and 15 plus cisplatin 80 mg/m2 on Day 2 (arm A) or Day 15 (arm B) every 28 days. RESULTS: All the patients were assessable for toxicity (arm A/arm B: 151/177 cycles; median, 4 of 5 cycles per patient), and the following Grade 3-4 toxicities were reported (percentage of cycles in arm A vs. arm B): anemia, 7.9% and 2.3% (P <0.05); leukopenia, 6.0% and 6.7%; thrombocytopenia, 15.0% and 1.6% (P <0.01); no World Health Organization (WHO) Grade 3-4 nonhematologic toxicities were observed. These side effects led to gemcitabine dose reductions in 35.1% of courses in arm A and 22.0% of courses in arm B (P <0.05) and to gemcitabine omissions in 28.5% of courses in arm A versus 7.3% of courses in arm B (P <0.01). Dose intensities (DIs) of gemcitabine were 607.5 mg/m2/week in arm A and 711.6 mg/m2/week in arm B (P <0.01); DIs of cisplatin were 18.1 mg/m2/week in arm A and 18.8 mg/m2/week in arm B. The total delivered doses of gemcitabine were 9315.5 mg/m2 in arm A and 12,631.0 mg/m2 in arm B (P <0.01); the total delivered doses of cisplatin were 277.1 mg/m2 in arm A and 333.0 mg/m2 in arm B (P <0.01). Response rates according to intention to treat were 40.4% (95% confidence interval [CI], 25.5-55.3) in arm A and 45% (95% CI, 29.5-60.5) in arm B. The overall median duration of response was 7.4 months; the median time to disease progression was 6 months (95% CI, 3-9) in arm A and 9 months (95% CI, 4-14) in arm B (P <0.02); the median overall survival was 10 months (95% CI, 7.0-12.5) in arm A and 17 months (95% CI, 13.0-21.6) in arm B (P <0.01); the 1-year survival rates were 34% and 63%, respectively. CONCLUSIONS: Our data show that arm B (cisplatin on Day 15) is less toxic than arm A (cisplatin on Day 2) and allows the administration of significantly higher total doses and dose intensities of chemotherapy. No significant differences in response rates were observed between the two schedules; patients on arm B experienced a significantly more prolonged progression free and overall survival; however, the study was not powered to detect differences in these outcomes. (C) 2000 American Cancer Society.

Original languageEnglish
Pages (from-to)1714-1719
Number of pages6
JournalCancer
Volume89
Issue number8
DOIs
Publication statusPublished - Oct 15 2000

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gemcitabine
Cisplatin
Appointments and Schedules
Confidence Intervals
Carcinoma
Lung
Poisons
Leukopenia
Thrombocytopenia
Disease-Free Survival
Disease Progression
Anemia
Survival Rate
Drug Therapy

Keywords

  • Cisplatin
  • Gemcitabine
  • Nonsmall cell lung carcinoma
  • Randomized trial

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A randomized study comparing two different schedules of administration of cisplatin in combination with gemcitabine in advanced nonsmall cell lung carcinoma. / Ricci, Sergio; Antonuzzo, Andrea; Galli, Luca; Tibaldi, Carmelo; Bertuccelli, Maurizio; Pegna, Andrea Lopes; Petruzzelli, Stefano; Bonifazi, Vittorio; Orlandini, Cinzia; Conte, Pier Franco.

In: Cancer, Vol. 89, No. 8, 15.10.2000, p. 1714-1719.

Research output: Contribution to journalArticle

Ricci, Sergio ; Antonuzzo, Andrea ; Galli, Luca ; Tibaldi, Carmelo ; Bertuccelli, Maurizio ; Pegna, Andrea Lopes ; Petruzzelli, Stefano ; Bonifazi, Vittorio ; Orlandini, Cinzia ; Conte, Pier Franco. / A randomized study comparing two different schedules of administration of cisplatin in combination with gemcitabine in advanced nonsmall cell lung carcinoma. In: Cancer. 2000 ; Vol. 89, No. 8. pp. 1714-1719.
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abstract = "BACKGROUND: This randomized trial was designed to investigate the feasibility, toxicity, and activity of two different schedules of gemcitabine plus cisplatin in previously untreated patients with advanced (International Union Against Cancer (UICC) Stage IIIB-IV) nonsmall cell lung carcinoma (NSCLC). METHODS: From February 1997 to September 1998, 82 patients with advanced NSCLC were entered onto the study and were randomized to gemcitabine 1000 mg/m2 on Days 1, 8, and 15 plus cisplatin 80 mg/m2 on Day 2 (arm A) or Day 15 (arm B) every 28 days. RESULTS: All the patients were assessable for toxicity (arm A/arm B: 151/177 cycles; median, 4 of 5 cycles per patient), and the following Grade 3-4 toxicities were reported (percentage of cycles in arm A vs. arm B): anemia, 7.9{\%} and 2.3{\%} (P <0.05); leukopenia, 6.0{\%} and 6.7{\%}; thrombocytopenia, 15.0{\%} and 1.6{\%} (P <0.01); no World Health Organization (WHO) Grade 3-4 nonhematologic toxicities were observed. These side effects led to gemcitabine dose reductions in 35.1{\%} of courses in arm A and 22.0{\%} of courses in arm B (P <0.05) and to gemcitabine omissions in 28.5{\%} of courses in arm A versus 7.3{\%} of courses in arm B (P <0.01). Dose intensities (DIs) of gemcitabine were 607.5 mg/m2/week in arm A and 711.6 mg/m2/week in arm B (P <0.01); DIs of cisplatin were 18.1 mg/m2/week in arm A and 18.8 mg/m2/week in arm B. The total delivered doses of gemcitabine were 9315.5 mg/m2 in arm A and 12,631.0 mg/m2 in arm B (P <0.01); the total delivered doses of cisplatin were 277.1 mg/m2 in arm A and 333.0 mg/m2 in arm B (P <0.01). Response rates according to intention to treat were 40.4{\%} (95{\%} confidence interval [CI], 25.5-55.3) in arm A and 45{\%} (95{\%} CI, 29.5-60.5) in arm B. The overall median duration of response was 7.4 months; the median time to disease progression was 6 months (95{\%} CI, 3-9) in arm A and 9 months (95{\%} CI, 4-14) in arm B (P <0.02); the median overall survival was 10 months (95{\%} CI, 7.0-12.5) in arm A and 17 months (95{\%} CI, 13.0-21.6) in arm B (P <0.01); the 1-year survival rates were 34{\%} and 63{\%}, respectively. CONCLUSIONS: Our data show that arm B (cisplatin on Day 15) is less toxic than arm A (cisplatin on Day 2) and allows the administration of significantly higher total doses and dose intensities of chemotherapy. No significant differences in response rates were observed between the two schedules; patients on arm B experienced a significantly more prolonged progression free and overall survival; however, the study was not powered to detect differences in these outcomes. (C) 2000 American Cancer Society.",
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author = "Sergio Ricci and Andrea Antonuzzo and Luca Galli and Carmelo Tibaldi and Maurizio Bertuccelli and Pegna, {Andrea Lopes} and Stefano Petruzzelli and Vittorio Bonifazi and Cinzia Orlandini and Conte, {Pier Franco}",
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TY - JOUR

T1 - A randomized study comparing two different schedules of administration of cisplatin in combination with gemcitabine in advanced nonsmall cell lung carcinoma

AU - Ricci, Sergio

AU - Antonuzzo, Andrea

AU - Galli, Luca

AU - Tibaldi, Carmelo

AU - Bertuccelli, Maurizio

AU - Pegna, Andrea Lopes

AU - Petruzzelli, Stefano

AU - Bonifazi, Vittorio

AU - Orlandini, Cinzia

AU - Conte, Pier Franco

PY - 2000/10/15

Y1 - 2000/10/15

N2 - BACKGROUND: This randomized trial was designed to investigate the feasibility, toxicity, and activity of two different schedules of gemcitabine plus cisplatin in previously untreated patients with advanced (International Union Against Cancer (UICC) Stage IIIB-IV) nonsmall cell lung carcinoma (NSCLC). METHODS: From February 1997 to September 1998, 82 patients with advanced NSCLC were entered onto the study and were randomized to gemcitabine 1000 mg/m2 on Days 1, 8, and 15 plus cisplatin 80 mg/m2 on Day 2 (arm A) or Day 15 (arm B) every 28 days. RESULTS: All the patients were assessable for toxicity (arm A/arm B: 151/177 cycles; median, 4 of 5 cycles per patient), and the following Grade 3-4 toxicities were reported (percentage of cycles in arm A vs. arm B): anemia, 7.9% and 2.3% (P <0.05); leukopenia, 6.0% and 6.7%; thrombocytopenia, 15.0% and 1.6% (P <0.01); no World Health Organization (WHO) Grade 3-4 nonhematologic toxicities were observed. These side effects led to gemcitabine dose reductions in 35.1% of courses in arm A and 22.0% of courses in arm B (P <0.05) and to gemcitabine omissions in 28.5% of courses in arm A versus 7.3% of courses in arm B (P <0.01). Dose intensities (DIs) of gemcitabine were 607.5 mg/m2/week in arm A and 711.6 mg/m2/week in arm B (P <0.01); DIs of cisplatin were 18.1 mg/m2/week in arm A and 18.8 mg/m2/week in arm B. The total delivered doses of gemcitabine were 9315.5 mg/m2 in arm A and 12,631.0 mg/m2 in arm B (P <0.01); the total delivered doses of cisplatin were 277.1 mg/m2 in arm A and 333.0 mg/m2 in arm B (P <0.01). Response rates according to intention to treat were 40.4% (95% confidence interval [CI], 25.5-55.3) in arm A and 45% (95% CI, 29.5-60.5) in arm B. The overall median duration of response was 7.4 months; the median time to disease progression was 6 months (95% CI, 3-9) in arm A and 9 months (95% CI, 4-14) in arm B (P <0.02); the median overall survival was 10 months (95% CI, 7.0-12.5) in arm A and 17 months (95% CI, 13.0-21.6) in arm B (P <0.01); the 1-year survival rates were 34% and 63%, respectively. CONCLUSIONS: Our data show that arm B (cisplatin on Day 15) is less toxic than arm A (cisplatin on Day 2) and allows the administration of significantly higher total doses and dose intensities of chemotherapy. No significant differences in response rates were observed between the two schedules; patients on arm B experienced a significantly more prolonged progression free and overall survival; however, the study was not powered to detect differences in these outcomes. (C) 2000 American Cancer Society.

AB - BACKGROUND: This randomized trial was designed to investigate the feasibility, toxicity, and activity of two different schedules of gemcitabine plus cisplatin in previously untreated patients with advanced (International Union Against Cancer (UICC) Stage IIIB-IV) nonsmall cell lung carcinoma (NSCLC). METHODS: From February 1997 to September 1998, 82 patients with advanced NSCLC were entered onto the study and were randomized to gemcitabine 1000 mg/m2 on Days 1, 8, and 15 plus cisplatin 80 mg/m2 on Day 2 (arm A) or Day 15 (arm B) every 28 days. RESULTS: All the patients were assessable for toxicity (arm A/arm B: 151/177 cycles; median, 4 of 5 cycles per patient), and the following Grade 3-4 toxicities were reported (percentage of cycles in arm A vs. arm B): anemia, 7.9% and 2.3% (P <0.05); leukopenia, 6.0% and 6.7%; thrombocytopenia, 15.0% and 1.6% (P <0.01); no World Health Organization (WHO) Grade 3-4 nonhematologic toxicities were observed. These side effects led to gemcitabine dose reductions in 35.1% of courses in arm A and 22.0% of courses in arm B (P <0.05) and to gemcitabine omissions in 28.5% of courses in arm A versus 7.3% of courses in arm B (P <0.01). Dose intensities (DIs) of gemcitabine were 607.5 mg/m2/week in arm A and 711.6 mg/m2/week in arm B (P <0.01); DIs of cisplatin were 18.1 mg/m2/week in arm A and 18.8 mg/m2/week in arm B. The total delivered doses of gemcitabine were 9315.5 mg/m2 in arm A and 12,631.0 mg/m2 in arm B (P <0.01); the total delivered doses of cisplatin were 277.1 mg/m2 in arm A and 333.0 mg/m2 in arm B (P <0.01). Response rates according to intention to treat were 40.4% (95% confidence interval [CI], 25.5-55.3) in arm A and 45% (95% CI, 29.5-60.5) in arm B. The overall median duration of response was 7.4 months; the median time to disease progression was 6 months (95% CI, 3-9) in arm A and 9 months (95% CI, 4-14) in arm B (P <0.02); the median overall survival was 10 months (95% CI, 7.0-12.5) in arm A and 17 months (95% CI, 13.0-21.6) in arm B (P <0.01); the 1-year survival rates were 34% and 63%, respectively. CONCLUSIONS: Our data show that arm B (cisplatin on Day 15) is less toxic than arm A (cisplatin on Day 2) and allows the administration of significantly higher total doses and dose intensities of chemotherapy. No significant differences in response rates were observed between the two schedules; patients on arm B experienced a significantly more prolonged progression free and overall survival; however, the study was not powered to detect differences in these outcomes. (C) 2000 American Cancer Society.

KW - Cisplatin

KW - Gemcitabine

KW - Nonsmall cell lung carcinoma

KW - Randomized trial

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