- Title
- Preoperative cisplatin, fluorouracil, and docetaxel with or without radiotherapy after poor early response to cisplatin and fluorouracil for resectable oesophageal adenocarcinoma (AGITG DOCTOR): results from a multicentre, randomised controlled phase II trial
- Creator
- Barbour, A. P.; Walpole, E. T.; Mai, G. T.; Barnes, E. H.; Watson, D. I.; Ackland, S. P.; Martin, J. M.; Burge, M.; Finch, R.; Karapetis, C. S.; Shannon, J.; Nott, L. M.; Varma, S.; Marx, G.; Falk, G. L.; Gebski, V.; Oostendorp, M.; Wilson, K.; Thomas, J.; Lampe, G.
- Relation
- NHMRC.1011782 http://purl.org/au-research/grants/nhmrc/1011782
- Relation
- Annals of Oncology Vol. 31, Issue 2, p. 236-245
- Publisher Link
- http://dx.doi.org/10.1016/j.annonc.2019.10.019
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2020
- Description
- Background: Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. Patients and methods: Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) =35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1: 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). Results: Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. Conclusions: EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy.
- Subject
- chemotherapy; gastro-oesophageal junction adenocarcinoma; metabolic response; neoadjuvant therapy; oesophageal adenocarcinoma; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1439081
- Identifier
- uon:40816
- Identifier
- ISSN:0923-7534
- Language
- eng
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