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Addition of tirapazamine to cisplatin chemoradiotherapy did not improve PFS in cervical cancer
The addition of the hypoxic cell sensitizer tirapazamine to a cisplatin chemoradiotherapy regimen did not improve PFS in patients with cervix cancer compared with cisplatin chemoradiotherapy alone, according to study results.
The prospective, randomized phase 3 trial — conducted by the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group — evaluated 402 patients with stage IB2 or IIA (tumor size >4 cm) or IIB, IIIB or IVA cervical carcinoma restricted to the pelvis.
Researchers randomly assigned patients to one of two regimens:
- Cisplatin 40 mg/m2 on days 1, 8, 15, 22, 29 and 36; or
- Tirapazamine 290 mg/m2 and cisplatin 75 mg/m2 on days 1, 15, and 29, and tirapazamine 220 mg/m2 on days 8, 10, 12, 22, 24 and 26 of chemoradiotherapy.
PFS served as the primary outcome measure. OS and treatment-related toxicity were secondary endpoints.
Of 402 enrolled patients, 379 were eligible for the intent-to-treat analysis. Enrollment was closed on Sept. 9, 2009, due to lack of the study drug.
Median follow-up was 28.3 months. At 3 years, PFS was 63% for the tirapazamine/cisplatin radiotherapy group and 64.4% for the cisplatin radiotherapy group (P=.7869). Also at 3 years, OS was 70.5% in the tirapazamine/cisplatin chemoradiotherapy arm and 70.6% in the cisplatin radiotherapy arm (P=.8333).
An interim safety analysis revealed a statistically significant increase in grade 3/grade 4 leukopenia, as well as gastrointestinal toxicities, in the tirapazamine/cisplatin radiotherapy arm. A subsequent dose reduction in the experimental arm eliminated this disparity in toxicity between the groups.
“For women with locally advanced cervical cancer, no regimen has been shown to be superior to cisplatin chemoradiotherapy,” the researchers wrote. “Despite theoretic advantages of adding tirapazamine to cisplatin in this patient population, this trial did not demonstrate the superiority of the tirapazamine/cisplatin regimen compared with cisplatin chemoradiotherapy.”
Disclosure: The researchers report no relevant financial disclosures.