Background
Phase III RCT (GOG 109). 268 patients enrolled, 243 assessable. Stage IA2, IB, or IIA cervical carcinoma initially treated with radical hysterectomy and pelvic lymphadenectomy, with high-risk features: positive pelvic lymph nodes, positive surgical margins, or microscopic parametrial involvement. Enrolled 1991–1996.
Interventions and follow up
Arm A: Adjuvant pelvic RT 49.3 Gy in 29 fractions (standard pelvic field)
Arm B: Pelvic RT 49.3 Gy + concurrent cisplatin 70 mg/m² IV bolus + 5-FU 1,000 mg/m²/d × 96-hour infusion q3wk × 4 cycles (cycles 1–2 concurrent with RT)
Primary endpoint: Progression-free survival and overall survival
mFollow up: Median ~42 month
Arm B: Pelvic RT 49.3 Gy + concurrent cisplatin 70 mg/m² IV bolus + 5-FU 1,000 mg/m²/d × 96-hour infusion q3wk × 4 cycles (cycles 1–2 concurrent with RT)
Primary endpoint: Progression-free survival and overall survival
mFollow up: Median ~42 month
Results
4-year PFS: 63% RT alone vs 80% RT + CT, HR 2.01 for RT alone vs RT+CT, P=.003
4-year OS: 71% RT alone vs 81% RT + CT, HR 1.96, P=.007
4-year OS: 71% RT alone vs 81% RT + CT, HR 1.96, P=.007
Adverse events
Main adverse events: Grade 3–4 hematologic toxicity significantly higher with concurrent CT (23% vs 2%). Grade 3–4 GI toxicity more frequent with CT (23% vs 13%). No significant difference in late GU/GI toxicity. No treatment-related deaths.
Conclusions
Concurrent cisplatin-based chemoradiation significantly improves PFS and OS compared with pelvic radiotherapy alone in high-risk post-hysterectomy cervical cancer. This trial, along with concurrent RTOG 9001 and GOG 120, triggered a 1999 NCI Clinical Announcement recommending cisplatin-based concurrent chemoradiotherapy as standard for most cervical cancer patients requiring RT.
Key Limitations
Key Limitations: 5-FU infusion is logistically burdensome; weekly cisplatin alone (as in GOG 120) is now the preferred regimen in most centers. The trial did not compare different chemotherapy regimens. High-risk criteria (LN+, margin+, parametrial+) is now routinely treated with concurrent weekly cisplatin 40 mg/m² and IMRT, extrapolated from this trial. No quality-of-life data were reported.
Clinical Context
GOG 109 (Peters et al) is the landmark trial establishing concurrent chemoradiation as standard of care for high-risk post-hysterectomy cervical cancer. Combined with RTOG 9001 and GOG 120, it prompted a paradigm shift: simultaneous with the 1999 NCI Clinical Announcement that all women with locally advanced cervical cancer receiving RT should also receive cisplatin-based chemotherapy. Modern practice uses weekly cisplatin 40 mg/m² with IMRT, achieving equivalent efficacy with reduced toxicity vs the original bolus cisplatin+5-FU regimen.
References
References: Peters WA et al, J Clin Oncol 2000 (GOG 109)