Bone Marrow-Sparing Intensity Modulated Radiation Therapy with Concurrent Cisplatin for Stage Ib-Iva Cervical Cancer : An International Multi-Center Phase II Clinical Trial (Intertecc-2)
Mené sur 83 patientes atteintes d'un carcinome du col de l'utérus de stade IB-IVA (durée médiane de suivi : 26 mois), cet essai international de phase II évalue, par rapport à un traitement standard et du point de vue de la réduction de la toxicité gastro-intestinale et hématologique, l'intérêt d'un traitement combinant de façon concomitante une chimiothérapie par cisplatine et une radiothérapie avec modulation d'intensité et guidage à l'aide d'une tomographie numérique par émission de positrons
Purpose : To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. Methods : We enrolled patients with stage IB-IVA cervical carcinoma on a single-arm phase II trial involving eight centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy as indicated. The primary endpoint was the occurrence of either acute grade ≥ 3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiotherapy. A pre-planned subgroup analysis tested the hypothesis that positron emission tomography (PET)-based image-guided IMRT (IG-IMRT) lowers the risk of acute neutropenia. We also longitudinally assessed changes in quality of life. Results : From October 2011 to April 2015, 83 patients met eligibility criteria and initiated protocol therapy. Median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% CI, 18.2-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (p=0.012). The incidences of grade ≥ 3 neutropenia and clinically significant GI toxicity were 19.3% (95% CI, 12.2-29.0%) and 12.0% (95% CI, 6.7-20.8%), respectively. Compared to patients treated without IG-IMRT (N=48), patients treated with IG-IMRT (N=35) had significantly lower grade ≥ 3 neutropenia (8.6% vs. 27.1%, 2-sided chi-square p=0.035), and non-significantly lower grade ≥ 3 leukopenia (25.7% vs. 41.7%, p=0.13) and any grade ≥ 3 hematologic toxicity (31.4% vs. 43.8%, p=0.25). Conclusion : IMRT reduces acute hematologic and GI toxicity compared to standard treatment, with promising therapeutic outcomes. PET-guided IMRT reduces acute neutropenia.