Phase 1/2 dose escalating study of twice-monthly pemetrexed and gemcitabine in patients with advanced cancer and non-small cell lung cancer

Arkadiusz Z. Dudek, Timothy Larson, Michael J. McCleod, Daniel J. Schneider, Jonathan E. Dowell, Tarit K. Banerjee, Kishan J. Pandya, Jane L. Bromund, Ruqin Chen, Matthew J. Monberg, Coleman K. Obasaju

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

INTRODUCTION: Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study. METHODS: The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis. RESULTS: Maximum tolerated dose was gemcitabine 1500 mg/m, followed by pemetrexed 500 mg/m. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108-0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79-6.18), median survival was 10.1 month (95% CI: 5.95-14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%). CONCLUSIONS: Twice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients.

Original languageEnglish (US)
Pages (from-to)394-399
Number of pages6
JournalJournal of Thoracic Oncology
Volume3
Issue number4
DOIs
StatePublished - Apr 2008

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gemcitabine
Pemetrexed
Non-Small Cell Lung Carcinoma
Neoplasms
Survival
Disease Progression
Febrile Neutropenia
Maximum Tolerated Dose
Vitamin B 12
Neutropenia
Folic Acid
Fatigue
Steroids

Keywords

  • Dose escalation
  • Gemcitabine
  • Non-small cell lung cancer
  • Nonplatinum doublet
  • Pemetrexed
  • Twice-monthly

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Phase 1/2 dose escalating study of twice-monthly pemetrexed and gemcitabine in patients with advanced cancer and non-small cell lung cancer. / Dudek, Arkadiusz Z.; Larson, Timothy; McCleod, Michael J.; Schneider, Daniel J.; Dowell, Jonathan E.; Banerjee, Tarit K.; Pandya, Kishan J.; Bromund, Jane L.; Chen, Ruqin; Monberg, Matthew J.; Obasaju, Coleman K.

In: Journal of Thoracic Oncology, Vol. 3, No. 4, 04.2008, p. 394-399.

Research output: Contribution to journalArticle

Dudek, AZ, Larson, T, McCleod, MJ, Schneider, DJ, Dowell, JE, Banerjee, TK, Pandya, KJ, Bromund, JL, Chen, R, Monberg, MJ & Obasaju, CK 2008, 'Phase 1/2 dose escalating study of twice-monthly pemetrexed and gemcitabine in patients with advanced cancer and non-small cell lung cancer', Journal of Thoracic Oncology, vol. 3, no. 4, pp. 394-399. https://doi.org/10.1097/JTO.0b013e318169cdc4
Dudek, Arkadiusz Z. ; Larson, Timothy ; McCleod, Michael J. ; Schneider, Daniel J. ; Dowell, Jonathan E. ; Banerjee, Tarit K. ; Pandya, Kishan J. ; Bromund, Jane L. ; Chen, Ruqin ; Monberg, Matthew J. ; Obasaju, Coleman K. / Phase 1/2 dose escalating study of twice-monthly pemetrexed and gemcitabine in patients with advanced cancer and non-small cell lung cancer. In: Journal of Thoracic Oncology. 2008 ; Vol. 3, No. 4. pp. 394-399.
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abstract = "INTRODUCTION: Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study. METHODS: The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis. RESULTS: Maximum tolerated dose was gemcitabine 1500 mg/m, followed by pemetrexed 500 mg/m. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8{\%} (95{\%} CI: 0.108-0.341), and the clinical benefit rate (CR + PR + SD) was 64.2{\%}. Median time to disease progression was 4.6 months (95{\%} CI: 2.79-6.18), median survival was 10.1 month (95{\%} CI: 5.95-14.09, censorship = 20.75{\%}), and 1-year survival was 41.0{\%}. Common grade 3 or 4 adverse events ({\%} of patients) were neutropenia (28.3{\%}), fatigue (22.6{\%}), and febrile neutropenia (9.4{\%}). CONCLUSIONS: Twice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients.",
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T1 - Phase 1/2 dose escalating study of twice-monthly pemetrexed and gemcitabine in patients with advanced cancer and non-small cell lung cancer

AU - Dudek, Arkadiusz Z.

AU - Larson, Timothy

AU - McCleod, Michael J.

AU - Schneider, Daniel J.

AU - Dowell, Jonathan E.

AU - Banerjee, Tarit K.

AU - Pandya, Kishan J.

AU - Bromund, Jane L.

AU - Chen, Ruqin

AU - Monberg, Matthew J.

AU - Obasaju, Coleman K.

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N2 - INTRODUCTION: Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study. METHODS: The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis. RESULTS: Maximum tolerated dose was gemcitabine 1500 mg/m, followed by pemetrexed 500 mg/m. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108-0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79-6.18), median survival was 10.1 month (95% CI: 5.95-14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%). CONCLUSIONS: Twice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients.

AB - INTRODUCTION: Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study. METHODS: The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis. RESULTS: Maximum tolerated dose was gemcitabine 1500 mg/m, followed by pemetrexed 500 mg/m. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108-0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79-6.18), median survival was 10.1 month (95% CI: 5.95-14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%). CONCLUSIONS: Twice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients.

KW - Dose escalation

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KW - Non-small cell lung cancer

KW - Nonplatinum doublet

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KW - Twice-monthly

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