In recent years, perioperative strategies and neoadjuvant protocols have achieved significant advantages in terms of overall survival in patients with advanced oesophagogastric cancer. With the exception of one randomised trial
, the proportion of individual localisations remains unclear, because all other trials enrolled patients with adenocarcinoma of the oesophagus, of the oesophagogastric junction and of the stomach. Hence this trial was designed to specifically address the issue of gastroesophageal tumours. In the treatment of gastroesophageal tumours, neoadjuvant RCT can achieve tumour shrinkage, leading to an increase of R0 resection rates, which in turn increases time to overall survival or even chance for cure. At the time this trial was designed, little data were available that assessed oxaliplatin and docetaxel with regards of safety and efficacy. Therefore, the aim of our study was to investigate the safety and tolerability of perioperative RCT with docetaxel and oxaliplatin in patients with tumours of the oesophagogastric junction.
Overall, the treatment regimen using oxaliplatin and docetaxel in combination with radiotherapy was well tolerated, with most frequently observed ≥ CTC grade 3 drug related adverse events being nausea (25%), vomiting (21%) and fatigue (21%). Hematological toxicities of > CTC grade 3 were observed to a lesser extent with thrombopenia in 8% of patients and leukopenia in 4% of patients.
Chemotherapy for GEJ tumours as part of combined RCT was previously based on cisplatin and 5-fluorouracil. Using CF as a neoadjuvant treatment (for 2 cycles prior to surgery and for a total of 6 cycles in case of good tolerability), neutropenia (20.2%) occurred in more than 10% of patients in a trial by Ychou et al.
. In another trial, using CF as sole treatment, neutropenia (57%), stomatitis (27%), and lethargy (14%) were reported for a substantial number of patients
. A study by Cunningham
 has shown that replacing cisplatin for oxaliplatin for treatment of advanced gastric cancer can significantly lower the incidence of toxic side effects. Even it is not possible to directly compare chemotherapy alone with its combination with radiation, docetaxel plus oxaliplatin reported less toxicities and less proportions of deaths due to adverse events than its triple combination with capacitabine in a recent randomized phase II trial
. Despite its inferiority in efficacy, such a double protocol may thus be a better combination partner in RCT. Comparably, the RCT combination of paclitaxel and carboplatin has recently been studied in the CROSS-trial
 randomizing 363 patients to either neoadjuvant radiochemotherapy followed by surgery, or surgery alone. Here, even if esophageal cancers were included mainly, gastroesophagel junctions tumors were also addressed. Toxicities in this study were also low, with hematologic toxicities occurring in 7% of patients and non-hematologic toxicities in less than 5% of patients.
Overall, combinations of taxanes and/or oxaliplatin with concurrent radiotherapy have been investigated only in a limited number of investigations
[20–22]. Spigel et al
 reported nausea and vomiting in 16%, and fatigue in 12% of patients treated with oxaliplatin, docetaxel and capecitabine. They have also found a significant amount of other drug related ≥ CTC grade 3 toxicities (anorexia, dehydration, esophagitis, and pulmonary symptoms). Solomon et al.
 also reported fatigue (25%) and diarrhea (31%) to be the most frequently observed events, along with nausea (6.25%). These toxicity data are comparable with our observations and show that RCT with oxaliplatin and docetaxel can be safely administered with a dose of 20 mg/m2 docetaxel and 50 mg/m2 oxaliplatin as in DL2, but higher doses of docetaxel lead to more haematological and non-hematological toxicities. Comparably, doses of onother preoperative RCT phaseI/II study corresponded to our DL1 for docetaxel and oxaliplatin, however with a lower radiation dose but additionally combined with capecitabine
In our trial, the progression-free survival of 6.5 months was somewhat lower than expected from other trials
[24, 25], while the 16.3 months overall survival compared to the rates reported by others
[7, 8], but was significantly lower than reported for the CROSS trial, where a median overall survival of 49 months in the RCT arm and 26 months in the surgery alone arm was achieved
. It should be noted that no final conclusions can be drawn with respect to treatment efficacy out of our study with a relatively low number of patients and wide confidence intervals. Again, 25% of the patients did not undergo surgery for various reasons (insufficient performance status, concomitant medical conditions and patient request). Even though this rate is substantially higher than the rate observed in the CROSS trial, where only 10% of neoadjuvant RCT treated patients could not be resected, it is comparable to those achieved in other trials