Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix
Alfonso Dueñas-González, Firuza Patel, Helen Barraclough, Juan C. Alcedo, Juan J. Zarbá, Julie M. Blair, Luis Casanova, Mauro Orlando*, Semir Beslija, Shahid Hameed, พิทยา ภมรเวชวรรณ
Eli Lilly Interamerica, Tronador 4890, Piso 12, Buenos Aires 1430, Argentina; e-mail: mauro@lilly.com
บทคัดย่อ
Purpose: To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.
Patients and Methods: Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score 70 were randomly assigned to arm A (cisplatin 40 mg/m2 and gemcitabine 125 mg/m2 weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m2 on day 1, plus gemcitabine, 1,000 mg/m2 on days 1 and 8) or to armB (cisplatin and concurrent XRT followed by BCT only; dosing same as for armA).
Results: BetweenMay 2002 andMarch 2004, 515 patients were enrolled (arm A, n= 259; arm B, n =256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P= .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A.
Conclusion: Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.
ที่มา
Journal of Clinical Oncology ปี 2554, May ปีที่: 13 ฉบับที่ 29 หน้า 1678-1685