Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer

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/m 2 ; n ¼ 398) or placebo plus cisplatin (75 mg/m 2 ; n ¼ 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 placebocisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P ¼ .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 ¼ .166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n ¼ 347) led to longer OS and PFS than placebo-cisplatin (n ¼ 343; 8.4 vs 6.7 months; HR, 0.83; P ¼ .026; 4.0 vs 3.0 months; HR, 0.84; P ¼ .044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n ¼ 86) resulted in longer OS and PFS than placebo-cisplatin (n ¼ 106; 9.9 vs 6.1 months; HR, 0.59; P ¼ .002; 4.0 vs 3.4 months; HR, 0.73; P ¼ .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 intentto-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. Cancer 2012;118:4694-705.

To treat or not to treat: balancing therapeutic outcomes, toxicity and quality of life in patients with recurrent and/or metastatic head and neck cancer

“…Finally, a recent phase III, randomized trial compared cisplatin and pemetrexed to cisplatin plus placebo as a first-line treatment for M/RHNC patients. 12 The study failed to meet its primary endpoint of OS, and analysis of QOL as a secondary endpoint revealed no significant changes from baseline, or in any individual symptoms, as assessed by FACT-H&N.…”

“…Finally, randomized trials comparing monotherapy versus combination therapy have been unable to confirm the superiority of any one regimen versus another (Figures B and C). [6][7][8][9][10][11][12] In fact, although RRs for cisplatin combined with 5-fluorouracil (5-FU) were consistently superior to other combinations and single agents in randomized trials, median survival durations did not significantly improve in a corresponding manner ( Table 1). Emergence of taxanes did little to advance the therapeutic landscape: a randomized phase III study revealed no differences in either response or survival between the standard cisplatin/ 5-FU regimen and cisplatin/paclitaxel ( Figure C).…”

“…Similarly, in a placebocontrolled trial, cisplatin and pemetrexed failed to demonstrate a statistically significant improvement in survival when compared to cisplatin in an intent-to-treat population; moreover, the RR and median overall survival (OS) were numerically lower than historical data with cisplatin/5-FU. 12 Options for second-line treatment for patients with M/RHNC are very limited. Due to poor performance status and high symptom burden, many patients receive only BSC after failure of first-line therapy.…”

Cisplatin-Based Chemotherapy Options for Recurrent and/or Metastatic Squamous Cell Cancer of the Head and Neck

“…Further analysis demonstrated that patients with a performance status (PS) (a measure of activity and ability to self-care developed by ECOG,) 6 of 0 or 1 exhibited significant improvement of OS vs. patients with a PS of 2. 27 …”

Comparison of pemetrexed plus cisplatin with gemcitabine plus docetaxel in refractory/metastatic osteosarcoma: Clinical outcomes from a retrospective database monitored in a single institute

“…A phase II study has demonstrated that approximately one-third of patients with relapsed osteosarcoma survived for at least 1 year after pemetrexed treatment ( 32 ). Furthermore, several studies have demonstrated that in head/neck cancer and malignant pleural mesothelioma, pemetrexed plus cisplatin combination treatment may prolong survival times in certain patients compared with treatment with pemetrexed or cisplatin alone ( 33 – 35 ). Since cisplatin is one of the most active and widely used drugs in the treatment of high-grade osteosarcoma, the pemetrexed plus cisplatin combination may have improved efficacy compared with cisplatin alone.…”