Lay Summary: I review otions for metastatic cervical cancer with the focus on the TPF regimen.
Although there have been important advances in the management of women with cervical cancer, the optimal treatment for patients with locally recurrent and metastatic disease is still problematic, and there are relatively few randomized trials to guide treatment decisions. There are a large number of chemotherapeutic agents with "activity" in metastatic cervical cancer. Cisplatin is the single most active agent to treat cervical cancer. In the Gynecologic Oncology Group (GOG) studies, involving approximately 800 patients, cisplatin was associated with a response rate of 29%. The response rate was greater at 31% with 100 mg/m2 compared with 21% at 50 mg/m2, but this was not associated with any significant improvement in progression-free or overall survival. The response rate of other platinum compounds, such as carboplatin, is possibly lower (15%), but the two agents have not been compared in a randomized trial. Cisplatin is associated with response rates of 20%-30% and a median survival of about 7 months. The impact of chemotherapy on palliation and survival is unclear. There have not been any randomized studies comparing chemotherapy with best supportive care or studies that have specifically investigated the impact of chemotherapy on symptom control and quality of life. One study demonstrated that the combination of cisplatin and methotrexate was associated with a significant increase in survival compared with a single inactive agent, hydroxyurea. In another relatively small study of cisplatin-based chemotherapy, it was demonstrated that, while only 30% of patients had an objective response to treatment, 67% had palliation of their pain.
A number of new agents (e.g., paclitaxel, vinorelbine, irinotecan, and gemcitabine) have been combined with cisplatin in phase II studies in patients with either locally advanced and/or recurrent cervical cancer . High response rates have been observed (40%-66%), particularly among patients with locally advanced disease. Similar findings have been observed with older cisplatin-based combinations, and randomized trials are essential before adopting such combinations for routine use outside clinical trials. The preliminary results of a large GOG study comparing cisplatin alone (50 mg/m2) with cisplatin (50 mg/m2) plus paclitaxel (135 mg/m2 over 24 hours) in 280 patients with recurrent or stage IV B squamous cell carcinoma of the cervix were presented at the American Society of Clinical Oncology meeting in May 2001.The combination produced a significantly higher response rate compared with cisplatin alone (36.2% versus 19.4%, p = 0.002). The combination regimen also was associated with higher rates of complete response (20% versus 8%) and partial response (27% versus 18%). These higher response rates translated into a significantly longer progression-free survival (p = 0.001) but no significant difference in overall survival (median 9.7 versus 8.8 months). Interim results suggested that the combination also improved various health-related quality-of-life parameters, but the quality-of-life data were incomplete at the time of presentation. IV carboplatin, Taxol and 5FU (TPF) is a combination used successfully in head and neck squamous cell cancer but there is little support for its use for metastatic cervical cancer. Carboplatin with Taxol is listed by NCCN but not TPF.
Michael Friedlander, Michelle Grogan Guidelines for the Treatment of Recurrent and Metastatic Cervical Cancer The Oncologist, Vol. 7, No. 4, 342–347, August 2002
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