112 research outputs found
Hypofractionated image-guided breath-hold SABR (Stereotactic Ablative Body Radiotherapy) of liver metastases - clinical results
Purpose: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive therapy option for inoperable liver oligometastases. Outcome and toxicity were retrospectively evaluated in a single-institution patient cohort who had undergone ultrasound-guided breath-hold SABR. Patients and methods: 19 patients with liver metastases of various primary tumors consecutively treated with SABR (image-guidance with stereotactic ultrasound in combination with computer-controlled breath-hold) were analysed regarding overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC), acute and late toxicity. Results: PTV (planning target volume)-size was 108 +/- 109cm(3) (median 67.4 cm(3)). BED2 (Biologically effective dose in 2 Gy fraction) was 83.3 +/- 26.2 Gy (median 78 Gy). Median follow-up and median OS were 12 months. Actuarial 2-year-OS-rate was 31%. Median PFS was 4 months, actuarial 1-year-PFS-rate was 20%. Site of first progression was predominantly distant. Regression of irradiated lesions was observed in 84% (median time to detection of regression was 2 months). Actuarial 6-month-LC-rate was 92%, 1- and 2-years-LC-rate 57%, respectively. BED2 influenced LC. When a cut-off of BED2 = 78 Gy was used, the higher BED2 values resulted in improved local control with a statistical trend to significance (p = 0.0999). Larger PTV-sizes, inversely correlated with applied dose, resulted in lower local control, also with a trend to significance (p-value = 0.08) when a volume cut-off of 67 cm(3) was used. No local relapse was observed at PTV-sizes < 67 cm(3) and BED2 > 78 Gy. No acute clinical toxicity > degrees 2 was observed. Late toxicity was also <= degrees 2 with the exception of one gastrointestinal bleeding-episode 1 year post-SABR. A statistically significant elevation in the acute phase was observed for alkaline-phosphatase; in the chronic phase for alkaline-phosphatase, bilirubine, cholinesterase and C-reactive protein. Conclusions: A trend to statistically significant correlation of local progression was observed for BED2 and PTV-size. Dose-levels BED2 > 78 Gy cannot be reached in large lesions constituting a significant fraction of this series. Image-guided SABR (igSABR) is therefore an effective non-invasive treatment modality with low toxicity in patients with small inoperable liver metastases
Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial
Preclinical data suggest that the anti-tumour activity of capecitabine is enhanced by taxanes and mitomycin C through up-regulation of thymidine phosphorylase (TP). Here, we studied safety and efficacy of the combination of capecitabine with docetaxel and mitomycin C. Two dose levels (DL) were investigated: capecitabine 1000βmgβmβ2 b.i.d. on days 1β14, docetaxel 40βmgβmβ2 i.v. day 1, mitomycin C 4 or 6βmgβmβ2 i.v. day 1 (DL I or II). Cycles were repeated every 3 weeks. The primary aim was to determine the dose-limiting toxicities (DLT) during the first two treatment cycles and the maximum tolerated dose (MTD). A total of 46 patients (pts) refractory to standard therapies were enrolled, of whom the majority had gastrointestinal tumours (n=40). 14 pts had received β©Ύ3 lines of prior chemotherapy. At DL I, one out of six pts experienced DLT. At DL II, two out of six pts had DLT (mucositis grade 3). Thus, DL I was determined as MTD. Among a total of 37 pts treated on DL I the following toxicities were observed during cycles 1 and 2 (number of patients with grade 1/2/3/4 toxicity; NCI-CTC v. 3.0): anaemia 10/8/3/0, leucocytopenia 4/11/1/2, thrombocytopenia 0/1/2/0, diarrhoea 8/1/2/0, stomatitis/mucositis 3/3/1/0, nausea/vomiting 10/2/0/0, and hand-foot skin reaction 5/1/1/0. Of 30 pts who received at least two treatment cycles nine achieved complete or partial remissions, six pts achieved minor remissions, and seven pts had stable disease (tumour control rate 73%). Of note, four out of 10 patients with pancreatic cancer had partial remissions. In conclusion, capecitabine can safely be combined with docetaxel (40βmgβmβ2) and mitomycin C (4βmgβmβ2). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising
Hemolytic uremic syndrome following the infusion of oxaliplatin: case report
BACKGROUND: Oxaliplatin is a platinum derivative, which is used in the treatment of colorectal cancer. A small number of oxaliplatin-related hemolytic and/or thrombocytopenic reactions have been reported. We present a case of hemolytic-uremic syndrome that developed during the 4(th )cycle of combination chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin. CASE PRESENTATION: A 52-year-old-male was administered chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin for a Duke's stage C colorectal carcinoma. Three cycles of chemotherapy had been administered without complications when, at the beginning of the fourth cycle, the patient developed clinical and laboratory abnormalities consistent with the development of the hemolytic-uremic syndrome. Treatment was discontinued; the patient was managed with monitored IV hydration and loop diuretics, high dose corticosteroids and fresh frozen plasma infusions and recovered completely. CONCLUSION: The hemolytic-uremic syndrome may be a rare complication of oxaliplatin-based chemotherapy. Clinicians need to maintain a high index of suspicion to diagnose and treat this life-threatening adverse event
Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial
IMPORTANCE:
Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction.
OBJECTIVE:
To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection.
DESIGN, SETTING, AND PARTICIPANTS:
The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013.
INTERVENTIONS:
Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT.
MAIN OUTCOMES AND MEASURES:
The primary end point was overall survival.
RESULTS:
In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (nβ=β51), 63 (28-79) years in arm B (nβ=β60), and 65 (23-83) years in arm C (nβ=β127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (Pβ<β.001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients.
CONCLUSIONS AND RELEVANCE:
Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials.
TRIAL REGISTRATION:
clinicaltrials.gov identifier: NCT00849615.info:eu-repo/semantics/publishedVersio
Feasibility of Image-Guided Radiotherapy for Elderly Patients with Locally Advanced Rectal Cancer
PURPOSE: The study aims to assess the tolerance of elderly patients (70 years or older) with locally advanced rectal cancers to image-guided radiotherapy (IGRT). A retrospective review of 13 elderly patients with locally advanced rectal cancer who underwent preoperative chemoradiation using IGRT was performed. Grade 3-4 acute toxicities, survival, and long-term complications were compared to 17 younger patients (<70 years) with the same disease stage. RESULTS: Grade 3-4 hematologic toxicities occurred in 7.6% and 0% (pβ=β0.4) and gastrointestinal toxicities, and, in 15.2% and 5% (pβ=β0.5), of elderly and younger patients, respectively. Surgery was aborted in three patients, two in the elderly group and one in the younger group. One patient in the elderly group died after surgery from cardiac arrhythmia. After a median follow-up of 34 months, five patients had died, two in the elderly and three in the younger group. The 3-year survival was 90.9% and 87.5% (pβ=β0.7) for the elderly and younger group respectively. Two patients in the younger group developed ischemic colitis and fecal incontinence. There was no statistically significant difference in acute and late toxicities as well as survival between the two groups. CONCLUSIONS AND CLINICAL RELEVANCE: Elderly patients with locally advanced rectal cancers may tolerate preoperative chemoradiation with IGRT as well as younger patients. Further prospective studies should be performed to investigate the potential of IGRT for possible cure in elderly patients with locally advanced rectal cancer
A phase II study to determine the ability of gefitinib to reverse fluoropyrimidine resistance in metastatic colorectal cancer (the INFORM study)
There are data suggesting that inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase signalling may reverse resistance to fluoropyrimidine treatment. To investigate this further, the INFORM study was an open-label, non-comparative phase II study of gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE, USA) 250βmg daily in combination with 5-fluorouracil (5-FU administered as an intravenous 400βmgβmβ2 bolus injection followed by 2800βmgβmβ2 infusion over 46βh and folinic acid administered as a 350βmg infusion over 2βh) every 2 weeks for up to 12 cycles in 24 patients with metastatic colorectal cancer refractory to previous fluoropyrimidine treatment. There were no objective responses. The stable disease rate was 37.5% (95% CI: 18.80, 59.41), median progression-free survival measured 116 days and overall survival was 226 days. Quality of life was unchanged compared to baseline values, and the commonest toxicities were diarrhoea, rash and fatigue with 7 out of 24 (29%) patients having a grade 3 or 4 toxicity. Gefitinib does not sensitise patients with fluoropyrimidine refractory metastatic colorectal cancer to 5-FU chemotherapy
Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy
<p>Abstract</p> <p>Background</p> <p>For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor <it>(VEGF-R</it>) and Transketolase-like-1 (<it>TKTL1</it>) are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of <it>VEGFR-1</it>, <it>VEGFR-2 </it>and <it>TKTL1 </it>in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab.</p> <p>Methods</p> <p>Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy) were analysed by quantitative PCR.</p> <p>Results</p> <p>Significantly higher expression of <it>VEGFR-1/2 </it>was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High <it>TKTL1 </it>expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers.</p> <p>Conclusion</p> <p>High <it>TKTL-1 </it>expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.</p
Tumour-targeted nanomedicines: principles and practice
Drug targeting systems are nanometre-sized carrier materials designed for improving the biodistribution of systemically applied (chemo)therapeutics. Various different tumour-targeted nanomedicines have been evaluated over the years, and clear evidence is currently available for substantial improvement of the therapeutic index of anticancer agents. Here, we briefly summarise the most important targeting systems and strategies, and discuss recent advances and future directions in the development of tumour-targeted nanomedicines
Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan
Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250βmgβmβ2 twice daily) days 1β14 every 3 weeks and MMC (7βmgβmβ2 IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40β77), and 23 patients (78%) were performance status 0β1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6β6.2). Median overall survival was 9.3 months (95% CI: 6.9β11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule
Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study
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