Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: Final results of a randomized, double-blind, placebo-controlled, phase 3 study
Journal
Cancer
Journal Volume
118
Journal Issue
19
Pages
4694-4705
Date Issued
2012
Author(s)
Urba S.
Van Herpen C.M.L.
Sahoo T.P.
Shin D.M.
Licitra L.
Mezei K.
Reuter C.
Hitt R.
Russo F.
Chang S.-C.
Hossain A.M.
Frimodt-Moller B.
Koustenis A.
Abstract
BACKGROUND: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed-cisplatin for SCCHN. METHODS: In a double-blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m 2) plus cisplatin (75 mg/m2; n = 398) or placebo plus cisplatin (75 mg/m2; n = 397) to assess overall survival (OS) and secondary endpoints. RESULTS: Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P =.082). Median progression-free survival (PFS, months) was similar in both treatment arms (pemetrexed-cisplatin, 3.6; placebo-cisplatin, 2.8; HR, 0.88; 95% CI, 0.76-1.03; P =.166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n = 347) led to longer OS and PFS than placebo-cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P =.026; 4.0 vs 3.0 months; HR, 0.84; P =.044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n = 86) resulted in longer OS and PFS than placebo-cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P =.002; 4.0 vs 3.4 months; HR, 0.73; P =.047, respectively). Pemetrexed-cisplatin toxicity was consistent with studies in other tumors. CONCLUSIONS: Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-To-Treat population. However, in a prespecified subgroup analysis, pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers. ? 2012 American Cancer Society.
Subjects
cisplatin; clinical trial; head and neck cancer; pemetrexed; phase 3
Other Subjects
analgesic agent; antiinfective agent; cisplatin; erythropoietin; granulocyte colony stimulating factor; granulocyte macrophage colony stimulating factor; pemetrexed; placebo; adult; aged; anemia; anorexia; article; cancer combination chemotherapy; cancer patient; confidence interval; controlled study; diarrhea; double blind procedure; drug efficacy; fatigue; febrile neutropenia; female; hazard ratio; head and neck squamous cell carcinoma; human; intention to treat analysis; Karnofsky Performance Status; kidney failure; leukopenia; major clinical study; male; metastasis; monotherapy; multiple cycle treatment; nausea; neutropenia; oropharynx cancer; overall survival; phase 3 clinical trial; priority journal; progression free survival; randomized controlled trial; recurrent cancer; thrombocytopenia; vomiting; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Double-Blind Method; Female; Glutamates; Guanine; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Treatment Outcome
Type
journal article