Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: Final report of a phase II trial

George R. Simon, Claire F. Verschraegen, Pasi A. Jänne, Corey J. Langer, Afshin Dowlati, Shirish M. Gadgeel, Karen Kelly, Gregory P. Kalemkerian, Anne M. Traynor, Guangbin Peng, John Gill, Coleman K. Obasaju, Hedy L. Kindler

Research output: Contribution to journalArticle

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Abstract

Purpose: Pemetrexed in combination with cisplatin is approved for the treatment of pleural mesothelioma and is active in malignant peritoneal mesothelioma (MPeM). Pemetrexed and gemcitabine are synergistic in preclinical models, but the activity of this combination in MPeM is unknown. This clinical study assessed safety and efficacy of pemetrexed plus gemcitabine in chemotherapy-naïve patients with MPeM. Patients and Methods: Treatment consisted of gemcitabine 1,250 mg/m2 on days 1 and 8, and pemetrexed 500 mg/m2 on day 8, administered immediately before gemcitabine. Treatment was repeated every 21 days for six cycles or until disease progression. All patients received folic acid, vitamin B12, and dexamethasone supplementation. End points included tumor response, toxicity, time to disease progression (TTPD), and overall survival (OS). Disease control rate (DCR) was also calculated. Results: Twenty patients were enrolled between December 2002 and May 2004. The confirmed response rate was 15% (95% CI, 3.2% to 37.9%), with three patients experiencing a partial response. The DCR was 50% (95% CI, 27.2% to 72.8%). The most common grade 3 to 4 nonhematologic toxicities included fatigue (20%), constipation (10%), vomiting (10%), and dehydration (10%). Hematologic toxicities included grade 3 to 4 neutropenia (60%) and febrile neutropenia (10%). One patient death was attributed to treatment. Median TTPD and OS times were 10.4 months and 26.8 months, respectively. Conclusion: The combination of pemetrexed plus gemcitabine was active in patients with MPeM with a notably high incidence of neutropenia. Median TTPD and OS seem promising. This regimen may provide an alternative to standard therapies, especially for patients who cannot tolerate a platinum-based regimen.

Original languageEnglish (US)
Pages (from-to)3567-3572
Number of pages6
JournalJournal of Clinical Oncology
Volume26
Issue number21
DOIs
StatePublished - 2008
Externally publishedYes

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gemcitabine
Pemetrexed
Mesothelioma
Drug Therapy
Neutropenia
Survival
Disease Progression
Therapeutics
Febrile Neutropenia
Constipation
Vitamin B 12
Platinum
Dehydration
Folic Acid
Dexamethasone
Cisplatin
Vomiting
Fatigue

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Simon, G. R., Verschraegen, C. F., Jänne, P. A., Langer, C. J., Dowlati, A., Gadgeel, S. M., ... Kindler, H. L. (2008). Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: Final report of a phase II trial. Journal of Clinical Oncology, 26(21), 3567-3572. https://doi.org/10.1200/JCO.2007.15.2868

Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma : Final report of a phase II trial. / Simon, George R.; Verschraegen, Claire F.; Jänne, Pasi A.; Langer, Corey J.; Dowlati, Afshin; Gadgeel, Shirish M.; Kelly, Karen; Kalemkerian, Gregory P.; Traynor, Anne M.; Peng, Guangbin; Gill, John; Obasaju, Coleman K.; Kindler, Hedy L.

In: Journal of Clinical Oncology, Vol. 26, No. 21, 2008, p. 3567-3572.

Research output: Contribution to journalArticle

Simon, GR, Verschraegen, CF, Jänne, PA, Langer, CJ, Dowlati, A, Gadgeel, SM, Kelly, K, Kalemkerian, GP, Traynor, AM, Peng, G, Gill, J, Obasaju, CK & Kindler, HL 2008, 'Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: Final report of a phase II trial', Journal of Clinical Oncology, vol. 26, no. 21, pp. 3567-3572. https://doi.org/10.1200/JCO.2007.15.2868
Simon, George R. ; Verschraegen, Claire F. ; Jänne, Pasi A. ; Langer, Corey J. ; Dowlati, Afshin ; Gadgeel, Shirish M. ; Kelly, Karen ; Kalemkerian, Gregory P. ; Traynor, Anne M. ; Peng, Guangbin ; Gill, John ; Obasaju, Coleman K. ; Kindler, Hedy L. / Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma : Final report of a phase II trial. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 21. pp. 3567-3572.
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abstract = "Purpose: Pemetrexed in combination with cisplatin is approved for the treatment of pleural mesothelioma and is active in malignant peritoneal mesothelioma (MPeM). Pemetrexed and gemcitabine are synergistic in preclinical models, but the activity of this combination in MPeM is unknown. This clinical study assessed safety and efficacy of pemetrexed plus gemcitabine in chemotherapy-na{\"i}ve patients with MPeM. Patients and Methods: Treatment consisted of gemcitabine 1,250 mg/m2 on days 1 and 8, and pemetrexed 500 mg/m2 on day 8, administered immediately before gemcitabine. Treatment was repeated every 21 days for six cycles or until disease progression. All patients received folic acid, vitamin B12, and dexamethasone supplementation. End points included tumor response, toxicity, time to disease progression (TTPD), and overall survival (OS). Disease control rate (DCR) was also calculated. Results: Twenty patients were enrolled between December 2002 and May 2004. The confirmed response rate was 15{\%} (95{\%} CI, 3.2{\%} to 37.9{\%}), with three patients experiencing a partial response. The DCR was 50{\%} (95{\%} CI, 27.2{\%} to 72.8{\%}). The most common grade 3 to 4 nonhematologic toxicities included fatigue (20{\%}), constipation (10{\%}), vomiting (10{\%}), and dehydration (10{\%}). Hematologic toxicities included grade 3 to 4 neutropenia (60{\%}) and febrile neutropenia (10{\%}). One patient death was attributed to treatment. Median TTPD and OS times were 10.4 months and 26.8 months, respectively. Conclusion: The combination of pemetrexed plus gemcitabine was active in patients with MPeM with a notably high incidence of neutropenia. Median TTPD and OS seem promising. This regimen may provide an alternative to standard therapies, especially for patients who cannot tolerate a platinum-based regimen.",
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T1 - Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma

T2 - Final report of a phase II trial

AU - Simon, George R.

AU - Verschraegen, Claire F.

AU - Jänne, Pasi A.

AU - Langer, Corey J.

AU - Dowlati, Afshin

AU - Gadgeel, Shirish M.

AU - Kelly, Karen

AU - Kalemkerian, Gregory P.

AU - Traynor, Anne M.

AU - Peng, Guangbin

AU - Gill, John

AU - Obasaju, Coleman K.

AU - Kindler, Hedy L.

PY - 2008

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