Summary Single-agent therapy with paclitaxel is effective against both squamous cell carcinoma and adenocarcinoma of the oesophagus. However, only limited data are available on the combination of paclitaxel with other cytotoxic drugs in this entity. Patients with unresectable stage l1l, recurrent or metastatic tumours were treated in a multicentre setting with paclitaxel 90 mg m-2 given over 3 h intravenously, followed by cisplatin 50 mg m-2. The courses were repeated every 14 days. Twenty patients with squamous cell carcinoma or adenocarcinoma of the oesophagus were evaluable for response. The overall remission rate was 40% (8/20), including 15% (3/20) clinically complete responses. Clinical benefit response, defined as relief of dysphagia and/or significant gain in weight, was achieved in 70% of the patients. Neutropenia of CTC grade 3 occurred only in 10% of the patients; no grade 4 neutropenia and no severe thrombocytopenia was encountered. CTC grade 4 neurotoxicity was seen in 5% of patients. Cisplatin/paclitaxel administered every 14 days, was effective in patients with poor prognosis oesophageal cancer and toxicity was acceptable.Keywords: paclitaxel; cisplatin; oesophageal cancer Several chemotherapeutic agents have been adequately investigated in patients with oesophageal cancer, predominantly with squamous cell histology. The most active drugs, with a response rate of at least 20%, are bleomycin, cisplatin, 5-fluorouracil, methotrexate, mitomycin-C and vindesine (Ajani, 1994). Currently, the combination of 5-fluorouracil and cisplatin is considered th6 standard treatment for squamous cell carcinoma of the oesophagus, with 50% of the patients responding to the treatment. Paclitaxel has demonstrated significant clinical activity against a variety of tumours. After a 24-h continuous infusion of 250 mg m-2 paclitaxel, Ajani et al (1994) achieved either a complete or partial response in 32% of oesophageal cancer patients.Only limited data are available on the combination of paclitaxel with other cytotoxic drugs in oesophageal cancer. Ajani et al (1995) have reported the preliminary results of a regimen combining paclitaxel with cisplatin and a continuous infusion of 5-fluorouracil. The overall remission rate was 44%. Gelmon and colleagues (Gelmon et al, 1996) established the maximum tolerated dose of paclitaxel in combination with cisplatin, repeated biweekly, in patients with metastatic breast cancer. The objective of our trial was to evaluate the response rate and the toxic effects of cisplatin/paclitaxel, repeated biweekly, in previously untreated patients with unresectable, recurrent or metastatic carcinoma of the oesophagus.
e16055 Background: In patients with mCRC, dynamics of response and disease progression may play a critical role in the understanding of long-term outcome. Depth of response (DpR), time to DpR and post-DpR survival represent innovative endpoints to evaluate response and disease dynamics. Methods: We evaluated DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR image to tumor progression or death), and post-DpR overall survival (pOS = DpR image to death) with special focus on BRAF mutational status in 66 patients. Results: BRAF wildtype (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (-57.6% vs. -40.8%, p = 0.013) with a comparable time to DpR (BRAF-WT 4.0 (95% CI 3.1-4.4) months vs. BRAF-MT 3.9 months (95% CI 2.5-5.5), p = 0.8852). pPFS was 6.5 (95% CI 4.7-8.4) versus 2.6 (95% CI 1.0-3.9) months in favor of BRAF-WT patients (HR: 0.24 (95% CI 0.11-0.53; p < 0.001). This also transferred into a significant difference in pOS (33.6 (95% CI 30.0-42.1) versus 5.4 (95% CI 4.7-16.1) months, HR: 0.27 (95% CI 0.13- 0.55); p < 0.001). Further data including primary tumor site will be presented at the meeting. Conclusions: BRAF-MT patients treated within the VOLFI-trial derive a less profound response to treatment as compared to BRAF-WT patients. The substantial difference in outcome according to BRAF status is evident after achievement of deepest response with BRAF-MT patients hardly deriving any further disease control beyond DpR. This is reflected by pPFS and pOS. Our observations hint towards aggressive tumor evolution in patients with BRAF-MT-tumors which may already be molecularly detectable at time of DpR. These findings somehow challenge the currently practiced aggressive treatment strategy of FOLFOXIRI-based 1st-line regimens as they may stimulate treatment resistance and suggest that close monitoring of BRAF-MT patients may include the continuous monitoring of clonal evolution.
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