Effectiveness and safety of combined therapy with pemetrexed and bevacizumab in recurrent and metastatic cervical cancer.
Аннотация
e17532 Background: In Uzbekistan, cervical cancer ranks third among all oncological diseases, with an incidence rate of 5.1 cases per 100,000 population in 2022. Among female malignancies, cervical cancer is second after breast cancer, with an incidence of 10.3 cases per 100,000 population. Pemetrexed, a multi-enzyme inhibitor, blocks the synthesis of purine and pyrimidine nucleotides necessary for tumor cell division and has proven effective in treating rapidly growing malignancies, including non-small cell lung cancer, gastric cancer, and gynecological cancers (ovarian cancer, endometrial cancer, cervical cancer). Methods: In a retrospective study, data from 11 patients with recurrent and metastatic cervical cancer, treated from February 2021 to March 2024, were analyzed. All patients had previously received standard first-line chemotherapy, including platinum derivatives combined with paclitaxel, but due to disease progression, second-line therapy was decided upon. The combined therapy included bevacizumab at a dose of 15 mg/kg and pemetrexed at a dose of 500 mg/m², administered intravenously on day 1 of each 21-day cycle. The treatment included 6 cycles. Prior to therapy, patients underwent standard evaluations, including general and biochemical blood tests, tumor marker assessments (SCC, CA-125), and imaging studies (CT or MRI) to assess stage and extent of disease. Results: Treatment analysis revealed no complete response. A partial response was observed in 3 patients (27.3%), disease stabilization in 7 patients (63.6%), and disease progression in 1 patient (9.1%). The overall objective response rate was 27.3%. Adverse effects included fatigue, nausea, loss of appetite, stomatitis, leukopenia, anemia, thrombocytopenia, skin reactions (rash), proteinuria, increased creatinine levels, and neurotoxicity. Most adverse effects were of grade I–II severity and were successfully managed with symptomatic therapy. Grade III reactions included leukopenia (18.2%), anemia (18.2%), thrombocytopenia (9.1%), hypertension (9.1%), and skin reactions (9.1%). The median progression-free survival (PFS) was 6.2 months (95% CI: 4.1–7.3), and the median overall survival (OS) was 9.7 months (95% CI: 6.7–10.8). Conclusions: Despite significant progress in the treatment of recurrent and metastatic cervical cancer, oncological outcomes remain insufficient to meet clinical needs. Combined therapy with pemetrexed and bevacizumab demonstrates moderate effectiveness and an acceptable safety profile, offering additional therapeutic options for patients with progressive disease.
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