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ABSTRACT: PURPOSE: To report on chronic adverse events (CAE) and quality of life (QOL) after radiochemotherapy (RCT) in patients with anal cancer (AC). PATIENTS AND METHODS: Of 83 patients who had received RCT at our department between 1988 and 2011, 51 accepted the invitation to participate in this QOL study. CAE were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 and QOL was assessed with the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire. RESULTS: CAE could be evaluated in 49 patients. There was a tendency toward a higher rate of grade 3 CAE in female patients, i.e. 18 out of 37 (49 %) vs. 2 out of 12 (17 %) male patients (p = 0.089). The most common grade 3 CAE were dyspareunia and vaginal symptoms (itching, burning and dryness) in 35 and 22 % of female patients, respectively, followed by stool incontinence in 13 % of all patients (6 out of 49). Both FACT-C and CAE information were available for 42 patients, allowing evaluation of the impact of CAE on QOL. The median total FACT-C score was 110 (40-132) out of a possible maximum of 136. The absence of grade 3 CAE (115 vs. 94, p = 0.001); an interval of ≥ 67 months after the end of the treatment (111 vs. 107, p = 0.010), no stool incontinence vs. grade 3 stool incontinence (111 vs. 74, p = 0.009), higher education (114 vs. 107, p = 0.013) and no dyspareunia vs. grade 3 dyspareunia (116 vs. 93, p = 0.012) were significantly associated with a higher median FACT-C score. CONCLUSION: The majority of AC patients treated with RCT have acceptable overall QOL scores, which are comparable to those of the normal population. Patients with grade 3 CAE-particularly dyspareunia and fecal incontinence-have a poorer QOL compared to patients without CAE. In order to improve long-term QOL, future strategies might aim at a reduction in dose to the genitalia and more intensive patient support measures.
Strahlentherapie und Onkologie 05/2013; · 3.56 Impact Factor
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S Lorenzen,
P Thuss-Patience,
S E Al-Batran,
F Lordick,
B Haller, T Schuster,
C Pauligk,
K Luley,
D Bichev,
G Schumacher,
N Homann
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ABSTRACT: Background
The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after neoadjuvant docetaxel/platin/fluoropyrimidine-based chemotherapy.Patients and methodsPatients received at least one cycle of chemotherapy for potentially operable disease. Pretreatment clinicopathologic factors and pCR were investigated. Disease-free survival (DFS), overall survival (OS) and tumor-related death were correlated with pCR.ResultsOne hundred twenty patients were included in this analysis. Eighteen patients (15%) achieved a pCR. Tumor localization in the EGJ was identified as the only significant predictor of pCR (P = 0.019). Median follow-up was 41.1 months. Median DFS and OS for all patients were 24.1 and 48.6 months, respectively. Median DFS for patients with a pCR was not reached versus 22.1 months non-pCR patients (hazard ratio, HR 0.38; 3-year DFS: 71.8% and 37.7%, respectively, P = 0.018). While OS was not significantly different, the risk for tumor-related death was significantly lower for pCR patients compared with non-pCR patients (3-year cumulative incidences of 6.4% and 45.4%, respectively, P = 0.009).ConclusionA pCR following preoperative docetaxel/platin/fluoropyrimidine indicates favorable outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ is associated with a higher pCR rate.
Annals of Oncology 04/2013; · 6.43 Impact Factor
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ABSTRACT: PURPOSE: The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. METHODS: A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). RESULTS: The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. CONCLUSION: New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced techniques in the neoadjuvant treatment of LAEC.
Strahlentherapie und Onkologie 02/2013; · 3.56 Impact Factor
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S Schwarzenböck,
D Sachs,
M Souvatzoglou, T Schuster,
R Nawroth,
G Weirich,
U Treiber,
H-J Wester,
S Ziegler,
M Schwaiger,
R Senekowitsch-Schmidtke,
B J Krause
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ABSTRACT: The aim of this study was to determine whether [11C]choline can be used for docetaxel therapy response assessment in a LNCaP-prostate cancer xenograft mouse model using [11C]choline small-animal PET/CT. Animals, methods: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [11C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [11C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [11C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/muscle (T/M) ratios (ROI T /ROI M = T/M ratio). Results: All LNCaP tumours could be visualized by [11C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [11C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/M mean ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [11C]choline uptake in the control group. Conclusion: Our results show that [11C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.
Nuklearmedizin 02/2013; 52(2). · 1.28 Impact Factor
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ABSTRACT: The goal of the present study was to assess the frequency and impact of replanning triggered solely by soft tissue changes observed on the daily setup mega-voltage CT (MVCT) in head and neck cancer (H&N) helical tomotherapy (HT).
A total of 11 patients underwent adaptive radiotherapy (ART) using MVCT. Preconditions were a soft tissue change > 0.5 cm and a tight mask. The dose–volume histograms (DVHs) derived from the initial planning kVCT (inPlan), the recalculated DVHs of the fraction (fx) when replanning was decided (actSit) and the DVHs of the new plan (adaptPlan) were compared. Assessed were the following: maximum dose (Dmax), minimum dose (Dmin), and mean dose (Dmean) to the planning target volume (PTV) normalized to the prescribed dose; the Dmean/fx to the parotid glands (PG), oral cavity (OC), and larynx (Lx); and the Dmax/fx to the spinal cord (SC) in Gy/fx.
No patient had palpable soft tissue changes. The median weight loss at the moment of replanning was 2.3 kg. The median PTV Dmean was 100% for inPlan, 103% for actSit, and 100% for adaptPlan. The PTV was always covered by the prescribed dose. A statistically significant increase was noted for all organs at risk (OAR) in the actSit. The Dmean to the Lx, the Dmean to the OC and the Dmax to the SC were statistically better in the adaptPlan. No statistically significant improvement was achieved by ART for the PGs. No significant correlations between weight and volume loss or between the volume changes of the organs to each other were observed, except a strong positive correlation of the shrinkage of the PGs (ρ = + 0.77, p = 0.005).
Soft tissue shrinkage without clinical palpable changes will not affect the coverage of the PTV, but translates into a higher delivered dose to the PTV itself and the normal tissue outside the PTV. The gain by ART in individual patients—especially in patients who receive doses close to the tolerance doses of the OAR—could be substantial.
Strahlentherapie und Onkologie 02/2012; 188(3):243-7. · 3.56 Impact Factor
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K Herrmann,
M Erkan,
M Dobritz, T Schuster,
J T Siveke,
A J Beer,
H J Wester,
R M Schmid,
H Friess,
M Schwaiger,
J Kleeff,
A K Buck
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ABSTRACT: Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET) and [(18)F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery.
A total of 46 patients with pancreatic tumours suspicious for malignancy and scheduled for resective surgery were recruited prospectively. In 41 patients, FLT PET and FDG PET/CT scans were performed. A diagnostic CT performed on a routine basis was available in 31 patients. FLT PET and FDG PET/CT emission images were acquired according to standard protocols. Tracer uptake in the tumour [FDG and FLT standardized uptake value (SUV)] was quantified by the region of interest (ROI) technique. For FDG PET/CT analysis, correct ROI placement was ensured via side-by-side reading of corresponding CT images.
Of 41 patients, 33 had malignancy, whereas 8 patients had benign disease. Visual analysis of FDG and FLT PET resulted in sensitivity values of 91% (30/33) and 70% (23/33), respectively. Corresponding specificities were 50% (4/8) for FDG PET and 75% (6/8) for FLT PET. In the subgroup of patients with contrast-enhanced CT (n = 31), sensitivities were 96% (PET/CT), 88% (CT alone), 92% (FDG PET) and 72% (FLT PET), respectively. Mean FLT uptake in all malignant tumours was 3.0 (range SUV(max) 1.1-6.5; mean FDG SUV(max) 7.9, range 3.3-17.8; p < 0.001).
For differentiation of pancreatic tumours, FDG PET and FDG PET/CT showed a higher sensitivity but lower specificity than FLT PET. Interestingly, visual analysis of FLT PET led to two false-positive findings by misinterpreting physiological bowel uptake as pathological FLT uptake in the pancreas. Due to the limited number of patients, the clinical value of adding FLT PET to the diagnostic workup of pancreatic tumours remains to be determined.
European Journal of Nuclear Medicine 01/2012; 39(5):846-51. · 4.53 Impact Factor
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ABSTRACT: The feasibility and effectiveness of radiotherapy in the management of recurrent esophageal carcinoma (REC) is reported.
A consecutive cohort of 54 patients with rcT1-4, rcN0-1, or cM0 recurrent esophageal carcinoma (69% squamous cell carcinoma, 31% adenocarcinoma) was treated between 1988 and 2010. The initial treatment for these patients was definitive radiochemotherapy, surgery alone, or neoadjuvant radiochemotherapy + surgical resection in 8 (15%), 33 (61%), and 13 (24%) patients, respectively. The median time to recurrence from initial treatment was 19 months (range 4-79 months). The site of the recurrence was anastomotic or local, nodal, or both in 63%, 30%, and 7% of patients, respectively. Salvage radio(chemo)therapy was carried out with a median dose of 45 Gy (range 30-68 Gy).
Median follow-up time for surviving patients from the start of R(C)T was 38 months (range 10-105 months). Relief of symptoms was achieved in 19 of 28 symptomatic patients (68%). The median survival time was 12 months (95% confidence interval (CI) 7-17 months) and the median recurrence-free interval was 8 months (95% CI 4-12 months). The survival rates at 1, 2, and 3 years were 55 ± 7%, 29 ± 6%, and 19 ± 5%, respectively. The recurrence-free survival rates at 1, 2, and 3 years were 44 ± 7%, 22 ± 6%, and 15 ± 5%, respectively. A radiation dose ≥ 45 Gy and conformal RT were associated with a better prognosis.
RT is feasible and effective in the management of recurrent esophageal carcinoma, especially for relief of symptoms. Toxicity is in an acceptable range. The outcome of REC is poor; however, long-term survival of patients with recurrent esophageal carcinoma after radiochemotherapy might be possible, even with a previous history of radiotherapy in the initial treatment. If re-irradiation of esophageal carcinoma is contemplated, three-dimensional conformal techniques and a minimum total dose of 45 Gy are recommended.
Strahlentherapie und Onkologie 01/2012; 188(2):136-42. · 3.56 Impact Factor
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ABSTRACT: The purpose of this study was to report the outcome of radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed 163 patients with T1-T4, N0-1, M0 ESCC who were treated between January 1988 and December 2006 at the Technische Universität München. One hundred sixty patients were inoperable due to a poor performance status, comorbidities or locally advanced unresectable disease. External beam radiation therapy (EBRT) was performed with (n= 146) or without (n= 17) systemic chemotherapy. Fifty-four patients received an additional boost with intraluminal brachytherapy (IBT). Surviving patients were followed for a median of 72 months (range 10-173 months). The estimated overall survival (OS) at 2 and 5 years was 27 ± 4% and 11 ± 3%, respectively. Loco-regional recurrence at the primary site was observed in 29% of patients (n= 47). The recurrence-free survival (RFS) at 2 and 5 years was 24 ± 3% and 9 ± 2%, respectively. In multivariate analyses, the ECOG performance status (P= 0.004), 3D conformal (vs conventional) radiotherapy (P= 0.031) and continuous standard fractionation (vs split-course radiotherapy, P= 0.048) were associated with a better OS. Simultaneous chemotherapy (P= 0.49) or IBT (P= 0.31) had no significant impact on survival. Outcome for patients with ESCC is poor. Despite the very unfavorable patient selection (poor performance status, high rate of comorbidities, and advanced disease), long-term survival with radio(chemo)therapy was achieved in about 10% of patients. The introduction of modern treatment techniques/modalities (3D conformal planning/ continuous standard fractionation) might be associated with better outcomes.
Diseases of the Esophagus 09/2011; 25(3):256-62. · 1.81 Impact Factor
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ABSTRACT: The standard treatment for resectable oesophageal squamous cell carcinoma (OSCC) is surgical resection with adequate lymphadenectomy. Most Western patients receive neoadjuvant chemotherapy or chemoradiotherapy (CRT). In recent years some patients have received CRT alone (definitive CRT, dCRT). This meta-analysis sought to clarify the benefits of neoadjuvant and definitive treatment for OSCC.
Eligible randomized controlled trials (RCTs) were identified using the Cochrane database, MEDLINE and Embase. Only RCTs with intention-to-treat analysis, and published hazard ratios (HRs) or estimates from survival data, were included.
Nine RCTs involving neoadjuvant CRT versus surgery, eight involving neoadjuvant chemotherapy versus surgery, and three involving neoadjuvant treatment followed by surgery or surgery alone versus dCRT were identified. The HR for overall survival was 0·81 (95 per cent confidence interval 0·70 to 0·95; P = 0·008) after neoadjuvant CRT and 0·93 (0·81 to 1·08; P = 0·368) after neoadjuvant chemotherapy. The likelihood of R0 resection was significantly higher after neoadjuvant treatment (CRT: HR 1·15, P = 0·043; chemotherapy: HR 1·16, P = 0·006). Morbidity rates were not increased after neoadjuvant CRT (HR 0·94, P = 0·363) but 30-day mortality was non-significantly higher with combined treatment. Morbidity (HR 1·03, P = 0·638) and mortality (HR 1·04, P = 0·810) rates after neoadjuvant chemotherapy and surgery did not differ from those after surgery alone. None of the RCTs reporting outcome after dCRT demonstrated a significant survival benefit, but treatment-related mortality rates were lower (HR 7·60, P = 0·007) than with neoadjuvant treatment followed by surgery or surgery alone.
For patients with resectable OSCC, a significant survival benefit for neoadjuvant CRT was evident, with no increase in morbidity rate. dCRT did not demonstrate any survival benefit over other curative strategies. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
British Journal of Surgery 04/2011; 98(6):768-83. · 4.61 Impact Factor
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F Lordick,
B Luber,
S Lorenzen,
S Hegewisch-Becker,
G Folprecht,
E Wöll,
T Decker,
E Endlicher,
N Röthling, T Schuster,
G Keller,
F Fend,
C Peschel
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ABSTRACT: Cetuximab enhances the efficacy of chemotherapy in several cancer types. This trial assessed the activity of cetuximab and chemotherapy in advanced gastric cancer.
Patients with previously untreated, metastatic, gastric cancer received cetuximab 400 mg m(-2) at first infusion followed by weekly infusions of 250 mg m(-2) combined with FUFOX (oxaliplatin 50 mg m(-2), 5-FU 2000 mg m(-2), and DL-folinic acid 200 mg m(-2) d1, 8, 15 and 22 qd36). The primary endpoint was tumour response.
Overall, 52 patients were enrolled. The most common grade 3/4 toxicities were diarrhoea (33%), and skin toxicity (24%). Efficacy was evaluable in 46 patients who showed a response rate of 65% (CI 95%: 50-79%) including four complete responses. Time to progression (TTP) was 7.6 months (CI 95%: 5.0-10.1 months) and overall survival (OS) was 9.5 months (CI 95%: 7.9-11.1 months). Epidermal growth factor receptor (EGFR) was detectable in 60% of tumours but showed no correlation with treatment outcome. A KRAS mutation was found in only 1 of 32 (3%) tumour samples analysed.
Cetuximab plus FUFOX showed an interesting high response rate in metastatic gastric cancer. Cetuximab plus platinum-fluoropyrimidine chemotherapy is at present being investigated in a phase III randomised controlled trial.
British Journal of Cancer 02/2010; 102(3):500-5. · 5.04 Impact Factor
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S Lorenzen, T Schuster,
R Porschen,
S-E Al-Batran,
R Hofheinz,
P Thuss-Patience,
M Moehler,
P Grabowski,
D Arnold,
T Greten,
L Müller,
N Röthling,
C Peschel,
R Langer,
F Lordick
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ABSTRACT: This study assessed the activity of the mAb cetuximab in combination with cisplatin and 5-fluorouracil (5-FU) in advanced esophageal squamous cell carcinoma.
For a maximum of six 29-day cycles, patients received cisplatin 100 mg/m(2), day 1, plus 5-FU 1000 mg/m(2), days 1-5 (CF), either alone or in combination with cetuximab (CET-CF; 400 mg/m(2) initial dose followed by 250 mg/m(2) weekly thereafter). The primary end point was tumor response. Tumor material was obtained for analysis of KRAS mutation status.
Sixty-two eligible patients were included, 32 receiving CET-CF and 30 CF. Cetuximab did not exacerbate grade 3/4 toxicity, except for rash (6% versus 0%) and diarrhea (16% versus 0%). The overall response rate according to RECIST criteria was 19% and 13% and the disease control rate 75% and 57% for the CET-CF and CF arms, respectively. With a median follow-up of 21.5 months, the median progression-free survival was 5.9 and 3.6 months and median overall survival 9.5 and 5.5 months for CET-CF and CF, respectively. No KRAS codon 12/13 tumor mutations were identified in 37 evaluated samples.
Cetuximab can be safely combined with CF chemotherapy and may increase the efficacy of standard CF chemotherapy.
Annals of Oncology 07/2009; 20(10):1667-73. · 6.43 Impact Factor
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S Lorenzen,
B Brücher,
F Zimmermann,
H Geinitz,
J Riera, T Schuster,
N Roethling,
H Höfler,
K Ott,
C Peschel,
J R Siewert,
M Molls,
F Lordick
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ABSTRACT: Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50 mg m(-2)) and continuous infusional 5-fluorouracil (CI-5FU; 225 mg m(-2)) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4-6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39-82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC.
British Journal of Cancer 10/2008; 99(7):1020-6. · 5.04 Impact Factor
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ABSTRACT: Three-weekly docetaxel is active in patients with advanced esophagogastric cancer but myelosuppression may make this schedule unsuitable for some patient groups such as elderly, pretreated, or poor performance status patients.
Eligible patients were chemonaive with Karnofsky index < or =70% and/or had received prior platinum-based chemotherapy. Docetaxel 35 mg/m(2) was administered on days 1, 8, 15, 22, 29, and 36 of a 49-day cycle. The primary endpoint was disease stabilization rate.
Of 46 patients (median age, 68.5 years; 47% > or =70 years) included, 87% had Karnofsky index < or =70 and 50% had prior treatment. The safety profile was acceptable. Principal grade 3/4 toxicities were leukopenia (9%) and fatigue (14%). Fifteen patients experienced no progression for > or =100 days (disease stabilization rate: 36%). Overall response rate was 9%; median overall survival was 7.0 months.
Weekly docetaxel was well tolerated and achieved disease stabilization in one-third of difficult-to-treat patients.
Critical Reviews in Oncology/Hematology 04/2008; 66(1):84-90. · 4.41 Impact Factor
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ABSTRACT: Epithelial ovarian cancer is the leading cause of death among female genital malignancies. Reduced expression of the cell adhesion molecule E-cadherin was previously shown to be associated with adverse prognostic features. The role of the E-cadherin repressor Snail in ovarian cancer progression remains to be elucidated. We analysed formalin-fixed and paraffin-embedded specimens of 48 primary ovarian tumours and corresponding metastases for expression of E-cadherin and Snail by immunohistochemistry. We found a significant correlation between E-cadherin expression in primary cancers and their corresponding metastases (P<0.001). This correlation was found for Snail expression as well (P<0.001). There was a significant (P=0.008) association of reduced E-cadherin expression in primary ovarian cancer with shorter overall survival. Similarly, Snail expression in corresponding metastases (P=0.047) was associated with reduced overall survival of the patients. Additionally, the group of patients showing reduced E-cadherin and increased Snail immunoreactivity in primary tumours and corresponding metastases, respectively, had a significantly higher risk of death (P=0.002 and 0.022, respectively) when compared to the patient group with the reference expression profile E-cadherin positive and Snail negative. Taken together, the results of our study show that the E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients.
British Journal of Cancer 01/2008; 98(2):489-95. · 5.04 Impact Factor
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ABSTRACT: An increase of the serum PSA-level is a sensitive in vitro marker for recurrent prostate cancer. However, it remains difficult to differentiate between local, regional or distant recurrent disease. The aim of this study was to assess the relationship between the detection rate of [(11)C]Choline-PET/CT and the serum PSA-level in patients with a biochemical recurrence of prostate cancer with the view towards localisation of recurrent disease.
Sixty-three patients (mean age, 68.8 +/- 6.9; range, 45-83 years) with biochemical recurrence after primary therapy for prostate cancer were included in the analysis. Mean PSA-levels were 5.9 +/- 9.7 ng/ml (range, 0.2-39 ng/ml; median, 2.15). Of the 63 patients, 17 were under anti-androgen therapy at the time of [(11)C]Choline PET/CT. Patients underwent a [(11)C]Choline-PET/CT study after injection of 656 +/- 119 MBq [(11)C]Choline on a Sensation 16 Biograph PET/CT scanner.
Of the 63 patients, 35 (56%) showed a pathological [(11)C]Choline uptake. The detection rate of [(11)C]Choline-PET/CT showed a relationship with the serum PSA-level: The detection rate was 36% for a PSA-value <1 ng/ml, 43% for a PSA-value 1-<2 ng/ml, 62% for a PSA-value 2-<3 ng/ml and 73% for a PSA-value >or=3 ng/ml. Anti-androgen therapy did not show a significant effect on the detection rate of [(11)C]Choline-PET/CT (p = 0.374).
As an important result our study shows that even for PSA-values <1.0 ng/ml the detection efficiency of [(11)C]Choline-PET/CT is 36%. Furthermore, the detection rate of [(11)C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [(11)C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy).
European Journal of Nuclear Medicine 01/2008; 35(1):18-23. · 4.53 Impact Factor
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ABSTRACT: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but high rates of hematologic toxicity in advanced gastric cancer. To reduce toxicity while maintaining the efficacy of DCF, we investigated split doses of docetaxel (T), cisplatin (P), leucovorin (L) and fluorouracil (F).
Chemotherapy-naive patients with advanced gastric-/esophageal adenocarcinomas received T 50 mg/m(2) and P 50 mg/m(2) on days 1, 15 and 29 and L 500 mg/m(2) plus F 2000 mg/m(2) weekly, every 8 weeks. Because significant dose reductions to <80% became necessary in 80% of patients, the regimen was amended after the first 15 patients to T 40 mg/m(2), P 40 mg/m(2), L 200 mg/m(2) and F 2000 mg/m(2). The primary endpoint was response rate.
Sixty patients were enrolled: 24 had locally advanced (LA) tumors and 36 had metastatic disease. Grade 3/4 toxicities included neutropenia (22%), febrile neutropenia (5%), diarrhea (20%) and lethargy (18%). The overall response rate was 47%. Twenty-three LA patients underwent secondary surgical resection (96%); complete resection was achieved in 87%. Overall, median time to progression and overall survival were 9.4 and 17.9 months, respectively (8.1 and 15.1 months, respectively, for patients with metastatic disease).
T-PLF regimen is highly active and has a favorable toxicity profile.
Annals of Oncology 10/2007; 18(10):1673-9. · 6.43 Impact Factor