Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma
Abstract
PURPOSE: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. PATIENTS AND METHODS: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. RESULTS: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P =.020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P =.001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P <.0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. CONCLUSION: Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.
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In a single-arm phase II trial of 150 kHz TTFields plus pemetrexed and platinum-based chemotherapy in malignant pleural mesothelioma, median overall survival and progression-free survival were 18.2 months and 7.6 months, respectively, compared with historical controls of 12.1 months and 5.7 months.
“In this single-arm phase II clinical trial, the median OS and PFS were 18.2 months and 7.6 months, respectively [13], compared to corresponding historical controls of 12.1 months and 5.7 months from a 2003 phase III clinical trial evaluating pemetrexed in combination with cisplatin in MPM [14].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [14]
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“The use of surgery in patients with MPM is very limited, the only approved therapy regimen includes pemetrexed plus cisplatin, and there is no standard second-line treatment [3,4].”
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- Authors
- Vogelzang, N. J., Rusthoven, J. J., Symanowski, J., Denham, C., Kaukel, E., Ruffie, P., Gatzemeier, U., Boyer, M., Emri, S., Manegold, C., Niyikiza, C., & Paoletti, P.
- Affiliations
- Eli Lilly (United States) (US)
- From the University of Chicago Cancer Research Center, Chicago, IL; Eli Lilly and Company, Indianapolis, IN; US Oncology, Dallas, TX; Allgemeines Krankenhaus Harburg, Hamburg; Krankenhaus Groβhansdorf, Groβhansdorf; and Thoraxklinik-Rohrbach, Heidelberg, Germany; Institut Gustave Roussy, Villejuif, France; Royal Prince Alfred Hospital, Camperdown, Australia; and Hacettepe University Medical Faculty, Ankara, Turkey.
- Venue
- Journal of Clinical Oncology
- Published
- 2003-07-15
- Volume
- 21
- Issue
- 14
- Pages
- 2636-2644
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2102627969
- Cited by
- 3,060
- References
- 39
- Citations by year
- 2026: 49 · 2025: 88 · 2024: 85 · 2023: 132 · 2022: 164 · 2021: 189 · 2020: 152 · 2019: 137 · 2018: 157 · 2017: 146 · 2016: 145 · 2015: 144 · 2014: 160 · 2013: 131 · 2012: 173
- FWCI
- 88.69
- Type
- journal article
- Language
- en
- Update notices
- new_edition (2023-04-17)
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- malignant pleural mesothelioma, pemetrexed, cisplatin, combination chemotherapy, survival, time to progression, response rate, folic acid, vitamin B12, chemotherapy toxicity, chemotherapy-naive patients
- MeSH terms
- Pemetrexed, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cisplatin, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Glutamates, Guanine, Humans, Male, Mesothelioma, Middle Aged, Neoplasm Staging, Pleural Neoplasms, Probability, Prognosis, Reference Values, Multivariate Analysis, Survival Analysis, Single-Blind Method, Treatment Outcome, Risk Assessment, Maximum Tolerated Dose
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