NEW YORK (Reuters Health) - Gemcitabine plus cisplatin prolongs progression-free survival in patients with recurrent or metastatic nasopharyngeal carcinoma, researchers report.
"The prognosis of recurrent or metastatic nasopharyngeal carcinoma is very poor, with a median overall survival of around 20 months," Dr. Li Zhang of the Sun Yat-sen University Cancer Center in Guangzhou, China told Reuters Health by email.
"For decades, the platinum doublet of 5-fluorouracil and cisplatin (has) reigned as the undisputed first-line chemotherapeutic combination. However, this regimen is limited by its common mucositis, the requirement of deep vein catheterization, and the relatively short duration of response," he explained.
"Recently, some efforts have been made to explore other novel agents such as gemcitabine, paclitaxel, docetaxel, vinorelbine, pemetrexed, and molecular-targeted therapies. However, no large head-to-head clinical trials are available to determine the most efficacious regimens," he said.
To investigate, Dr. Zhang and colleagues conducted a phase III trial in 22 hospitals in China comparing gemcitabine (1 g/m2 IV on days one and eight) and cisplatin (80 mg/m2 IV on day one) versus fluorouracil (4 g/m2 in continuous IV infusion over 96 hours) and cisplatin (80 mg/m2 IV on day one). Patients in both groups were treated once every three weeks for up to six cycles.
As reported online August 23 in The Lancet, 181 patients received the gemcitabine regimen and 181 received the fluorouracil regimen.
The average overall survival was 29.1 months for gemcitabine plus cisplatin compared with 20.9 months for fluorouracil plus cisplatin (hazard ratio, 0.62). Progression-free survival averaged 7.0 months in the gemcitabine group compared with 5.6 months for the fluorouracil group (HR, 0.55).
The safety analysis included 180 patients in the gemcitabine group and 173 patients in the fluorouracil group. The gemcitabine group experienced significantly more treatment-related grade 3 or 4 adverse events, including leukopenia (29% in the gemcitabine group versus 9% in the fluorouracil group); neutropenia (23% versus 13%); and thrombocytopenia (13% versus 2%).
By contrast, mucosal inflammation was greater for the fluorouracil group (14% versus 0% for gemcitabine). In addition, serious treatment-related adverse events occurred in 4% of patients in the gemcitabine group compared with 6% in the fluorouracil group. Three percent of patients in the gemcitabine group and 8% in the fluorouracil group discontinued treatment because of drug-related adverse events.
Dr. Zhang concluded, "Undoubtedly, the current study establishes GP as the new standard of first-line treatment of choice in recurrent or metastatic nasopharyngeal carcinoma."
Dr. Melvin Chua Lee Kiang of the National Cancer Institute Singapore, coauthor of a related editorial, commented to Reuters Health, "This is a seminal study for two main reasons - foremost, this is the first-ever randomized controlled phase III trial in metastatic nasopharyngeal carcinoma; and secondly, it was more than 10 years in the making since the first clinical reports suggesting that perhaps gemcitabine was a very effective drug in nasopharyngeal carcinoma."
"Because of this study, we now have a new standard first-line treatment in patients with metastatic disease," he wrote in an email.
"Looking ahead, we eagerly await the results of two ongoing clinical trials that will reveal if gemcitabine is equally efficacious in the non-metastatic curative setting," Dr. Kiang continued. "On the metastatic disease front, the most pertinent question in the current climate of cancer immunotherapy is whether immunotherapy offers synergism with gemcitabine to further improve first-line treatment responses."
Dr. Marc Cohen of Memorial Sloan Kettering Cancer Center in New York City, commented, "The management of recurrent or metastatic nasopharyngeal carcinoma is challenging. While the next frontier in patient care will be individualized care based on biomarkers and targeted therapy, this study gives compelling controlled data that cisplatin plus gemcitabine results in better progression-free survival than cisplatin plus fluorouracil . . . (and) should inspire physicians who use cisplatin and fluorouracil . . . to rethink their treatment strategy."
"However," he added, "clinicians in the U.S. and Europe should interpret the data with caution as (the) study was performed in China, a region where nasopharyngeal cancer is endemic. The epidemiology of the disease is distinct in the U.S. and Europe; therefore, further investigation in the U.S. and Europe should commence to address these questions."
Eli Lilly provided the gemcitabine used in the trial. Dr. Chang reported research support from Eli Lilly and other pharmaceutical companies.
SOURCE: http://bit.ly/2c58GQy and http://bit.ly/2caOqju
Lancet 2016.
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