Introduction Despite many efforts to develop new chemotherapies for metastatic upper gastrointestinal (GI) cancer, overall prognosis continues to be fatal, particularly in gastric and pancreatic cancer. Many of these patients deserve second-or third-line treatment after failure of first-line chemotherapy. Therefore, we analysed toxicity and response rate of weekly docetaxel after failed upfront regimes in these upper GI cancer patients. Patients and Methods Between 2001 and 2006, 18 patients received docetaxel based regimes (35 mg/m 2 weekly) after informed consent. Response rates were determined using RECIST criteria or tumor progression if clinically evident. Toxicities were graded based on NCI CTC criteria (version 2). Most patients had gastric cancer (13/18). The remaining entities comprised of bilio-pancreatic cancer (5/18). Results Docetaxel was administered as 2nd line therapy in 28% (5/18), 3rd line therapy in 56% (10/18) and 4th or 5th line therapy in 17% (3/18). The average docetaxel dose was 38 mg/m 2 (Median: 35 mg/m 2 ) once weekly. Over a treatment duration of 14.7 weeks, the average dosage was 58 gr per patient and week. Overall, docetaxel was well tolerated with only few chemotherapy-associated toxicities (Grade 3/4), including nausea (17%), polyneuropathy (17%), anorexia (11%), neutropenia (6%) and leukopenia (17%). Docetaxel administration did not achieve any complete responses (CR) and one (5.6%) partial response (PR) was seen (1/18). In addition 5 patients (27.8%) had stable disease (SD), thus inducing a tumor control rate of 33.3% (6/18). Median progression-free survival was 2.4 months for all patients, 2.1 months in the gastric-cancer and 2.4 months in the bilio-pancreatic cancer subgroups respectively. After first docetaxel administration median survival for all patients was 4.5 months, patients with gastric cancer survived for 4.9 months whereas patients suffering from bilio-pancreatic carcinoma survived for 4.2 months. However, taken together 27% (5/18) had a remarkable overall survival of more than 2.5 years. Discussion In severely pretreated patients, with documented chemoresistant GI tumors, weekly docetaxel was well tolerated, presented good tumor control rate and overall survival. Therefore, this regimen may be used as salvage treatment in individual patients with upper GI cancers.