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Competing Interests: Rupert Bartsch: advisory role in Astra-Zeneca, Celgene, Daiichi, Eisai, Eli-Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Puma, Roche, and Samsung; lecture honoraria from Accord, Astra-Zeneca, BMS, Celgene, Eli-Lilly, Novartis, Pfizer, Pierre-Fabre, Roche, and Sandoz; and research support from Daiichi, MSD, Novartis, and Roche. Veronique Dieras: consultant/advisory board for Roche/Genentech, Novartis, Lilly, Pfizer, AstraZeneca, Eisai, AbbVie, MSD, Daiichi Sankyo, and Seattle Genetics. Javier Cortes: consulting/advisor for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, and Kyowa Kirin; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, and Daiichi Sankyo; research funding to the institution from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffmann-La Roche, Guardanth Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma C, and Queen Mary University of London; and stock, patents, and intellectual property from MedSIR. Volkmar Müller: consultant for Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Tesaro, and Seattle Genetics and Nektar; and institutional research support from Novartis, Roche, Seattle Genetics, and Genentech. Thomas Ruhstaller: consultant/advisory boards for Roche/Genentech, Novartis, Lilly, and AstraZeneca.

Background: A phase I multicentre trial was conducted to define the recommended dose of capecitabine in combination with oxaliplatin and irinotecan (OCX) in metastatic colorectal cancer., Patients and Methods: Patients with performance status (PS) < 2 and adequate haematological, renal and liver function received oxaliplatin 70 mg/m(2) on days 1 and 15, irinotecan 100 mg/m(2) on days 8 and 22 and one of five dose levels (DL 1-5, between 800 and 1,600 mg/ m(2)) of capecitabine on days 1-29 every 5 weeks., Results: 23 patients received a median of 3 cycles. 3 dose-limiting toxicities occurred (DL 1: grade 3 (G3) elevated alkaline phosphatase; DL 5: 1 patient G4 hyperglycaemia/G3 diarrhoea and 1 sudden death). The most common severe adverse event was G3 diarrhoea (13%). Severe haematotoxicity was rare. Therapy was stopped mainly due to metastasectomy or tumour progression (7 patients each). 8 patients reached a partial response. Median time to progression and overall survival (OS) were 8.0 and 21.9 months, respectively., Conclusions: The recommended capecitabine dose in this schedule is 1,400 mg/m(2) daily. The OCX regimen is well tolerated. The response rate was surprisingly low with progression-free survival (PFS) and OS within the range of a triple combination. Further studies in combination with targeted agents are warranted.

Background: There is no standard treatment for patients with locally advanced esophageal carcinoma without systemic metastasis in whom surgery is no longer considered a reasonable option., Patients and Methods: Patients with cervical esophageal tumors, locally very advanced stage (T4 and/or M1a) or locally advanced (T3 and/or N+) with comorbidities were included., Therapy: 2 cycles of induction chemotherapy (cisplatin and docetaxel, both 75 mg/m(2) 3-weekly) followed by chemoradiation therapy (CRT) comprising a total radiation dose of 59.4 Gy together with docetaxel 15 mg/m(2) and cisplatin 25 mg/m(2) (5 weekly doses). Primary endpoint: Histologically proven freedom from local failure 6 months after CRT completion., Results: 21 patients were included: 12 had locally very advanced tumors, 3 had cervical esophagus tumors, and 6 were medically unfit for surgery. 18 patients completed therapy per protocol. Grade 3/4 toxicities during CRT were thrombopenia (10%) and dysphagia (15%). 1 patient died due to herpes simplex infection. The primary endpoint was achieved by 4 patients, 6 were alive after median follow-up of 34 months, and median survival was 16 months. Most patients experienced lasting improvement of dysphagia following induction chemotherapy., Conclusions: This regimen is feasible, showed clinically meaningful, long-lasting improvements in quality of life and resulted in long-term survival in 29% of the patients., (Copyright 2010 S. Karger AG, Basel.)

Background: Only responding patients benefit from preoperative therapy for locally advanced esophageal carcinoma. Early detection of non-responders may avoid futile treatment and delayed surgery., Patients and Methods: In a multi-center phase ll trial, patients with resectable, locally advanced esophageal carcinoma were treated with 2 cycles of induction chemotherapy followed by chemoradiotherapy (CRT) and surgery. Positron emission tomography with 2[fluorine-18]fluoro-2-deoxy-d-glucose (FDG-PET) was performed at baseline and after induction chemotherapy. The metabolic response was correlated with tumor regression grade (TRG). A decrease in FDG tumor uptake of less than 40% was prospectively hypothesized as a predictor for histopathological non-response (TRG > 2) after CRT., Results: 45 patients were included. The median decrease in FDG tumor uptake after chemotherapy correlated well with TRG after completion of CRT (p = 0.021). For an individual patient, less than 40% decrease in FDG tumor uptake after induction chemotherapy predicted histopathological non-response after completion of CRT, with a sensitivity of 68% and a specificity of 52% (positive predictive value 58%, negative predictive value 63%)., Conclusions: Metabolic response correlated with histopathology after preoperative therapy. However, FDG-PET did not predict non-response after induction chemotherapy with sufficient clinical accuracy to justify withdrawal of subsequent CRT and selection of patients to proceed directly to surgery., (Copyright 2009 S. Karger AG, Basel.)

Objectives: The purpose of this investigation was firstly to assess the overall frequency of subjectively experienced symptoms self-reported by patients receiving endocrine therapy and secondly to compare these symptoms with side effects assessed by clinicians in pivotal trials., Methods: Unselected patients with early and advanced breast cancer receiving endocrine therapy were approached consecutively during a routine outpatient visit. They received a questionnaire called Checklist for Patients with Endocrine Therapy (C-PET), a validated self-assessment tool to determine prespecified symptoms associated with endocrine therapy. Data on toxicity were also obtained from previously published trials., Results: 405 patients were approached and 373 agreed to participate in this study. Some symptoms were significantly more often recorded by the women in the adjuvant setting completing the C-PET than by physicians' reports in pivotal trials: hot flushes/sweats (C-PET 70%, ATAC 40% and BIG1-98 38%), low energy (C-PET 45%, ATAC 15% and BIG1-98 9%), fluid retention (C-PET 22% and BIG1-98 7%) and vaginal dryness (C-PET 30% and BIG1-98 3%). Similar differences were observed in the metastatic and adjuvant setting., Conclusions: A simple tool like the C-PET questionnaire is able to reflect the treatment burden of endocrine therapies and may be helpful to improve communication between patients and care providers. Some symptoms were significantly more often reported by the women in the C-PET than by physicians in pivotal trials.

Background: Herpes simplex virus (HSV) infections are frequent. However, HSV hepatitis is rare and may lead to a life-threatening condition., Case Report: A 68-year-old patient with a locally advanced and inoperable esophageal carcinoma was treated with induction chemotherapy and combined chemoradiation. After a total of 9 weeks of treatment, he developed fulminant liver failure of unknown origin and died a few days later. Surprisingly, the post mortem examination revealed an HSV infection of the esophagus and an HSV-associated necrotisizing hepatitis., Conclusion: In this immunocompromised patient, we postulate an HSV-associated esophagitis that led to viremia and fulminant hepatitis. Especially in immunocompromised hosts, HSV hepatitis should be considered in the differential diagnosis in patients with anicteric hepatitis and marked elevation of transaminases. A liver biopsy is the quickest and most definitive diagnostic tool to diagnose HSV hepatitis. If this is not possible because of severe coagulopathy, polymerase chain reaction for HSV DNA should be performed. Awaiting diagnosis, a prompt empirical treatment with acyclovir has to be discussed in case of a characteristic biochemical profile.

Objectives: Pegylated liposomal doxorubicin (PLD) has improved therapy options significantly, as it causes less myelosuppression, nausea, vomiting, and alopecia than conventional doxorubicin, while maintaining efficacy. The goal of this survey was to determine whether the use of PLD in a community-based patient group is comparable regarding chemotherapeutic doses and side effects to preselected study patients., Methods: 100 questionnaires were randomly sent to Swiss oncologists in private practices, general hospitals and university hospitals., Results: The patient cohort was heterogeneous with respect to prior treatments. PLD was an active agent in metastatic breast cancer and was well tolerated by the majority of patients. The most common non-hematological side effects were hand-foot syndrome (HFS) and mucositis while only patients receiving a dose of 50 mg/m(2) (recommended dose) experienced grade 4 HFS. The reported mean dose of PLD was 38.5 mg/m(2)., Conclusions: This community-based observational study supports previous reports indicating that PLD at a median dose of < or =40 mg/m(2) every 4 weeks is an active, well-tolerated agent in non-selected, pretreated patients with metastatic breast cancer., ((c) 2007 S. Karger AG, Basel)

Background: Skin metastases from gastric cancer are rare and generally occur at a very late stage in the course of the disease., Case Report: A 60-year-old patient with localized adenocarcinoma of the cardia (stage II) was primarily treated with extended total gastrectomy with transhiatal resection of the distal esophagus. 6 isolated skin metastases occurred on the head and on the thigh 2 years later. These lesions where all surgically removed. Morphologically and according to an extensive immunohistochemical comparison the skin lesions and the primary tumor were identical. The patient presented with dysphagia more than 6 years after the primary diagnosis, and a local recurrence was diagnosed. Again a surgical procedure was chosen and a transthoracal esophagectomy with intrathoracic esophagojejunostomy was performed. This patient remains free of symptoms and is clinically in complete remission 7.5 years after the primary diagnosis., Conclusion: We report a long-term disease-free survival of a patient with isolated cutaneous metastases of a gastric cancer. Usually the prognosis after occurrence of metastases to the skin is poor, but long-term survival after systemic therapy has been reported. This patient is clinically in remission more than 5 years after surgical resection of several cutaneous metastases and after successful resection of a local recurrence more than 1 year ago. One should be aware of such unusual clinical courses of a disease, and that the prognosis can deviate significantly from the average when the pattern of metastasis is unusual.