Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non–Small-Cell Lung Cancer Previously Treated With Chemotherapy
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PURPOSE: To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. PATIENTS AND METHODS: Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m(2) intravenously (i.v.) day 1 with vitamin B(12), folic acid, and dexamethasone or docetaxel 75 mg/m(2) i.v. day 1 with dexamethasone every 21 days. The primary end point was overall survival. RESULTS: Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance P =.105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months (P = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% v 5.3%; P <.001), febrile neutropenia (12.7% v 1.9%; P <.001), neutropenia with infections (3.3% v 0.0%; P =.004), hospitalizations for neutropenic fever (13.4% v 1.5%; P <.001), hospitalizations due to other drug related adverse events (10.5% v 6.4%; P =.092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P <.001) and all grade alopecia (37.7% v 6.4%; P <.001) compared with patients receiving pemetrexed. CONCLUSION: Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available.
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In a phase III second-line study, pemetrexed was non-inferior to docetaxel for OS (8.3 versus 7.9 months, HR 0.99, 95% CI 0.8-1.2) and had a better toxicity profile with lower neutropaenia, alopecia and gastrointestinal adverse events.
“A phase III second-line study demonstrated non-inferiority for OS between pemetrexed and docetaxel (8.3 versus 7.9 months, HR 0.99, 95% CI: 0.8-1.2).However, pemetrexed showed a better toxicity profile with a significantly lower rate of neutropaenia and alopaecia as well as lower rates of gastrointestinal AEs [86].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [86]
Comparable second-line options include pemetrexed for non-squamous cell carcinoma only, or docetaxel.
“Comparable options in the second line consist of pemetrexed (for NSCC only) [86] or docetaxel [I, B] [87].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [86]
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- Authors
- Hanna, N., Shepherd, F. A., Fossella, F. V., Pereira, J. R., De Marinis, F., von Pawel, J., Gatzemeier, U., Tsao, T. C. Y., Pless, M., Muller, T., Lim, H.-L., Desch, C., Szondy, K., Gervais, R., Shaharyar, Manegold, C., Paul, S., Paoletti, P., Einhorn, L., & Bunn, P. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- From Indiana University and the Hoosier Oncology Group; Eli Lilly and Company, Indianapolis, IN; The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of Colorado Cancer Center, Denver, CO; Virginia Cancer Institute, Richmond, VA; Princess Margaret Hospital and the University of Toronto, Toronto, Ontario, Canada; Instituto Arnaldo Vieira de Carvalho, Sao Paolo, Brazil; San Camillo-Forlanini Hospitals, Rome, Italy; Chang Gung Memorial Hospital, Taoyuan, Taiwan; University Hospital...
- Venue
- Journal of Clinical Oncology
- Published
- 2004-05-01
- Volume
- 22
- Issue
- 9
- Pages
- 1589-1597
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2134667653
- Cited by
- 2,426
- References
- 2
- Citations by year
- 2026: 17 · 2025: 30 · 2024: 25 · 2023: 45 · 2022: 62 · 2021: 42 · 2020: 60 · 2019: 63 · 2018: 88 · 2017: 109 · 2016: 121 · 2015: 152 · 2014: 175 · 2013: 171 · 2012: 159
- FWCI
- 110.67
- Type
- journal article
- Language
- en
- Update notices
- new_edition (2023-05-17)
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- pemetrexed, docetaxel, non-small cell lung cancer, second-line chemotherapy, overall survival, neutropenia, febrile neutropenia, hair loss, treatment toxicity, granulocyte colony-stimulating factor, progression-free survival, overall response rate, previously treated patients, dexamethasone
- MeSH terms
- Pemetrexed, Docetaxel, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Antineoplastic Agents, Phytogenic, Carcinoma, Non-Small-Cell Lung, Female, Glutamates, Guanine, Humans, Lung Neoplasms, Male, Middle Aged, Neutropenia, Survival Analysis, Treatment Outcome, Taxoids
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