Objective: Cisplatin (Cp) plus topotecan (Tc) is the first combination chemotherapy to demonstrate a survival advantage over cisplatin alone in advanced cervical cancer. Combining Cp and Tc with an epidermal growth factor receptor (EGFR) inhibitor such as cetuximab (Ce) may increase the activity of chemotherapy.
Methods: Patients with advanced cervical squamous cell cancer or adenocarcinoma and at least one measurable target received intravenous Cp 50 mg/m(2) on day 1 plus Tc 0.75 mg/m(2)/day from days 1 to 3 every 3 weeks combined with Ce (initial dose of 400 mg/m(2) followed by subsequent weekly dose of 250 mg/m(2)). Objective response rate according to RECIST criteria was the primary end point; safety, progression free survival (PFS) and overall survival (OS) were secondary end points.
Results: Between April and July 2007, 19 out of the 44 planned patients were accrued before the study was stopped early due to excessive toxicity. The most frequent adverse event was severe myelosuppression with grades 3-4 neutropenia (72%), grades 3-4 thrombocytopenia (61%), and grade 3 anemia (44.5%). The main grades 3-4 non-hematologic toxicities were infection (39%) and febrile neutropenia (28%), skin reactions (22%), renal toxicity (11%), and pulmonary embolism (11%). Five (28%) patients died during the treatment including 3 deaths related to treatment toxicity. Six (32%) evaluable patients achieved a partial response. The median times of PFS and OS were 172 and 220 days, respectively.
Conclusion: In this phase II trial, the combination Cp-Tc-Ce induced a high rate of serious adverse and/or fatal events at standard dose and schedule. Cetuximab plus platinum-based combination chemotherapy should be further explored with caution in the future in advanced cervix cancer.