Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

Abstract

Summary This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m 2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9-20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7-28.1 months; 95% CI: 3.9-7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B 12 supplementation.

Schedule-Dependent Synergistic Effect of Pemetrexed Combined with Gemcitabine against Malignant Pleural Mesothelioma and Non-Small Cell Lung Cancer Cell Lines

“…MTA has shown an antitumor effect against human tumor cells from various histotypes in vitro [4] and has also demonstrated certain clinical activities against a wide variety of human solid tumors, including non-small cell lung cancer (NSCLC) [5] , breast [6,7] , pancreatic [8] , gastric [9,10] , colorectal [10,11] as well as head and neck [12,13] cancers. The involvement of multiple targets may contribute to a broad spectrum of cytotoxic effects exhibited by MTA, and may be important for preventing the development of drug resistance.…”

A Dose Escalation Study of Gemcitabine plus Pemetrexed Administered Biweekly in Patients with Solid Tumors

“…The drug has been recently approved for the treatment of inoperable malignant mesothelioma [3]; moreover, pemetrexed has been registered for the second-line treatment of locally advanced or metastatic non-small cell lung cancer, since it has shown comparable efficacy but a better toxicity profile compared to docetaxel [4]. In addition, pemetrexed has shown significant activity against a broad spectrum of solid tumors [5,6,7,8,9,10,11,12,13]. Pemetrexed has a favorable toxicity profile although its use is associated with myelosuppression, gastrointestinal toxicity, skin rash and mucositis [14, 15].…”

Potential and Toxicity of Intravesical Pemetrexed: a Preclinical Study in Pigs

“…Pemetrexed in its systemic application has shown a broad spectrum of clinical activity in multiple tumor types in phase II and III studies, including mesothelioma (7,12), colorectal (13 -16), breast (17), non -small cell lung (5, 6), pancreatic, head and neck (18), and cervical cancers (19). Several dosing schedules have been tested systemically in phase I studies (3).…”