Phase II Study of Neoadjuvant Therapy with Docetaxel, Cisplatin, Panitumumab Plus Radiation Therapy Followed by Surgery in Patients with Locally Advanced Adenocarcinoma of the Distal Esophagus (ACOSOG Z4051)
Mené sur 65 patients atteints d'un adénocarcinome localement avancé de la partie distale de l'œsophage traité entre 2009 et 2011 (durée médiane de suivi : 26,3 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse pathologique complète, et la toxicité d'un traitement par docétaxel-cisplatine-panitumumab et radiothérapie avant une intervention chirurgicale
Purpose : Preoperative chemoradiotherapy (CRT) improves outcomes in patients with locally advanced but resectable adenocarcinoma of the esophagus. ACOSOG Z4051 evaluated CRT with docetaxel, cisplatin, and panitumumab (DCP) in this patient group with a primary endpoint of a pathologic complete response (pCR)≥35%. Patients and Methods : From 01/15/09 to 07/22/11, 70 patients with locally advanced but resectable distal esophageal adenocarcinoma were enrolled. Patients received docetaxel (40 mg/m2), cisplatin (40 mg/m2), and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7 and 9 with RT (5040 cGy, 180 cGy/day x 28d) beginning week 5. Resection was planned after completing CRT. PCR was defined as no viable residual tumor cells. Secondary objectives included near-pCR (≤ 10% viable cancer cells), toxicity, and overall and disease-free survival. Adverse events were graded using the CTCAE Version 3.0. Results : Five of 70 patients were ineligible. Of 65 eligible patients (59 M; median age 61), 11 did not undergo surgery, leaving 54 evaluable. PCR rate was 33.3% and near-pCR was 20.4%. 73% of patients completed DCP (n=70) and 92% completed RT. 48.5% had toxicity≥grade 4. Lymphopenia (43%) was most common. Operative mortality was 3.7%. ARDS was encountered in 2 pts (3.7%). At median follow-up of 26.3 months, median overall survival was 19.4 months and 3-yr overall survival was 38.6% (95% CI 24.5% to 60.8%). Conclusions : Neoadjuvant CRT with DCP is active (pCR+near-pCR=53.7%) but toxicity is significant. Further evaluation of this regimen in an unselected population is not recommended.