Influence of the department on the resection rate in palliative treatment of metastatic colorectal cancer (CRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13528-13528
Author(s):  
A. Wein ◽  
T. Liersch ◽  
R. Hofheinz ◽  
J. Fahlke ◽  
J. Wilke ◽  
...  
Keyword(s):  
Palliative Treatment ◽  
Distant Metastases ◽  
Phase Iii ◽  
Concomitant Treatment ◽  
Resection Rate ◽  
Treatment Groups ◽  
Tumour Extension ◽  
Prospective Phase ◽  
Palliative Situation ◽  
Adenocarcinoma Of The Colon

13528 Background: During the last years due to the application of Irinotecan, Oxaliplatin and “biologicals” for the first- and secondline treatment of CRC in palliative situation the efficacy of palliative treatment has considerably improved with an acceptable toxicity. The achievements of secondary metastatic resection after downsizing by palliative treatment have increasingly become the focus of interest in palliative patients and opened up new ways in terms of curative options (Folprecht et al. 2005; Wein et al. 2001). Here, we analyse the influence of different departments on the resection rate after palliative treatment. Methods: A prospective phase III trial in metastatic CRC with systemic treatment by 5-FU/sodium FA as a 24h-infusion (AIO) versus AIO plus Oxaliplatin followed by secondary metastatic resection. Trial start: 2000; end of trial: 2005. Randomized patients: n = 240 by 5 centers experienced in clinical trials. In order to achieve a homogeneous patient group, non-resectability of distant metastases was required according to pre-defined criteria. Stratification characteristics: In accordance to the participating departments; ECOG index 0.1 vs 2. Involvement of the hepatic tumour extension 25% vs other localisation; organ manifestation 1 vs > 1. Inclusion criteria: Definitively non-resectable metastases. Palliative first-line treatment: Histologically proven adenocarcinoma of the colon or rectum, unambiguous enlargement of metastatic masses in objective imaging procedures. At least one bidimensionally measurable tumour lesion. Age: > 18, < 75 years. Exclusion criteria: Concomitant treatment with other anti-neoplastic substances. Sensoric neuropathy. Results: Resected/randomized patients of 176 currently evaluable patients, both treatment groups combined: department (dep.) 01: 0/26 (0%), dep. 02: 10/27 (37.0%), dep. 03: 21/68 (30.9%), dep. 04: 8/43 (18.6%), dep. 05: 1/12 (8.3%), total: 40/176 (22.7%). Although in the total population, a remarkable resection rate could be achieved, the variation between the departments is high (p=.0043 for differences between departments). Conclusions: The resection rate after palliative CRC treatment essentially depends on the department. No significant financial relationships to disclose.

Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study.

1988 ◽  
Vol 6 (9) ◽  
pp. 1401-1410 ◽  
Author(s):  
A Rossi ◽  
R Molinari ◽  
P Boracchi ◽  
M Del Vecchio ◽  
E Marubini ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Randomized Study ◽  
Nasopharyngeal Cancer ◽  
Distant Metastases ◽  
Undifferentiated Carcinoma ◽  
Treatment Groups ◽  
Distant Failure ◽  
Curative Radiotherapy ◽  
Significant Difference ◽  
Base Of The Skull

To evaluate the effect of adjuvant chemotherapy in patients with local-regional nasopharyngeal carcinoma (NPC) (squamous or undifferentiated) in complete remission at the end of curative radiotherapy (RT) 229 patients were randomized from 1979 to 1983 in a multicenter study to no further therapy (116 patients) or a combination of vincristine, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (VCA) for six monthly cycles (113 patients). The RT and RT + VCA groups were well balanced for median age (50 v 49 years), histology (undifferentiated carcinoma, 73% v 70%), tumor extent (tumor limited to nasopharynx, 57% v 57%), and nodal extent (negative nodes 26% v 24%, nodes in the lower cervical levels, 17% v 16%). RT was delivered to the nasopharynx, the base of the skull, and bilateral cervical nodes using a split course technique over 10 weeks up to the dose of 60 to 70 Gy in involved sites and 50 Gy to negative nodes. Response to RT was evaluated within 65 days post-RT treatment. Analysis at 48 months did not show significant difference between the two treatment groups in terms of relapse-free survival (RT, 55.8%, RT + VCA, 57.7%, P = .45) and overall survival (RT, 67.3%, RT + VCA, 58.5%, P = .13). The pattern of relapse was similar in the two treatment arms. Distant metastases were the cause of treatment failure in about 50% of relapsing patients. Although the results of the present study did not show any benefit from VCA administered after curative RT, combined systemic chemotherapy should be further explored due to the high incidence of local and distant failure after intensive RT.

Abstract 5063: Cardiovascular Effects of Transdermal Testosterone in Postmenopausal Women

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
C Vitale ◽  
P Collins ◽  
G Marazzi ◽  
G Caminiti ◽  
I Lodhi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Hormone Replacement ◽  
Cardiovascular Effects ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Double Blind ◽  
Treatment Groups ◽  
Clinical Program ◽  
Large Phase

Testosterone Transdermal Patch (TTP) has been developed for the treatment of postmeno-pausal women (PMW) with hypoactive sexual desire disorder (HSDD). Since the cardiovascular (CV) effects of testosterone in women are still unclear we conducted a pooled analysis of the large phase III clinical program to evaluate the efficacy and safety of 300 μg/day TTP, alone or in association with hormone replacement therapy (HRT), versus placebo in surgical or natural PMW. Design & Methods: A total of 2795 women aged between 26 –70 years (mean age 52(SD=6.8) years) were included in 5 phase III randomized, double-blind, placebo-controlled clinical trials (treatment duration range 24 – 52 weeks) as part of the TTP Clinical program. 4 studies included PMW (natural and surgical, two each respectively) receiving HRT while 1 study was conducted without HRT, in either surgical or natural PMW. Women with known CV disorders were excluded from the studies. Changes from baseline in standard metabolic and CV risk factors were compared. The incidence of stroke, myocardial infarction (MI) and venous thromboembolism (VTE) alone or as a composite CV endpoint was assessed. Results: The 2795 PMW were randomized to receive either placebo (n=1297) or TTP (n=1498). Baseline mean BMI was 27 kg/m2 (SD=5.3 kg/m2) and 56% were naturally menopausal. The demographic and baseline parameters were similar among the treatment groups. No significant changes in CV risk factors (Total Cholesterol, Triglycerides, Insulin, Glucose, Systolic and Diastolic Blood Pressure) were detected during the study period, apart from a blunting of the increases in HDL-C by TTP at 24 and 52 weeks (Placebo 52-week mean change 2.59 mg/dl vs. TTP 52-week mean change 1.20 mg/dl, p<0.005) and of the decrease in LDL-C by TTP at 24 (p<0.05), but not at 52 weeks. During the double-blind (24 weeks), placebo-controlled period of the combined studies, 4 major CV events (2 MIs and 2 strokes) were reported in placebo patients and 3 (2 MIs and 1 stroke) in those receiving TTP. One VTE occurred in a patient receiving TTP and HRT. Conclusion: TTP therapy in these clinical trials did not adversely affect CV risk profile and did not change the risk of major CV events in these surgical and naturally PMW with or without concomitant HRT.

scholarly journals Neoadjuvant Chemotherapy Compared With Surgery Alone for Locally Advanced Cancer of the Stomach and Cardia: European Organisation for Research and Treatment of Cancer Randomized Trial 40954

2010 ◽  
Vol 28 (35) ◽  
pp. 5210-5218 ◽  
Author(s):  
Christoph Schuhmacher ◽  
Stephan Gretschel ◽  
Florian Lordick ◽  
Peter Reichardt ◽  
Werner Hohenberger ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Neoadjuvant Chemotherapy ◽  
Preoperative Chemotherapy ◽  
Survival Benefit ◽  
Locally Advanced ◽  
Postoperative Chemotherapy ◽  
Phase Iii ◽  
R0 Resection ◽  
Resection Rate

PurposePatients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.Patients and MethodsPatients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.ResultsThis trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).ConclusionThis trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).

scholarly journals MRI and Dose Selection in a Phase II Trial of Baricitinib with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis

2019 ◽  
Vol 46 (8) ◽  
pp. 887-895 ◽  
Author(s):  
Charles Peterfy ◽  
Julie DiCarlo ◽  
Paul Emery ◽  
Mark C. Genovese ◽  
Edward C. Keystone ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Joint Damage ◽  
Phase Iii ◽  
Cartilage Loss ◽  
Dose Selection ◽  
Mri Findings ◽  
Clinical Trial Registration ◽  
Treatment Groups ◽  
Link Type ◽  
Registration Number

Objective.Magnetic resonance imaging (MRI) was used in a phase IIb study of baricitinib in patients with RA to support dose selection for the phase III program.Methods.Three hundred one patients with active RA who were taking stable methotrexate were randomized 2:1:1:1:1 to placebo or once-daily baricitinib (1, 2, 4, or 8 mg) for up to 24 weeks. One hundred fifty-four patients with definitive radiographic erosion had MRI of the hand/wrist at baseline and at weeks 12 and 24. Two expert radiologists, blinded to treatment and visit order, scored images for synovitis, osteitis, bone erosion, and cartilage loss. Combined inflammation (osteitis + 3× synovitis score) and total joint damage (erosion + 2.5× cartilage loss score) scores were calculated. Treatment groups were compared using ANCOVA adjusting for baseline scores.Results.Mean changes from baseline to Week 12 for synovitis were −0.10, −1.50, and −1.60 for patients treated with placebo, baricitinib 4 mg, and baricitinib 8 mg, respectively (p = 0.003 vs placebo for baricitinib 4 and 8 mg). Mean changes for osteitis were 0.00, −3.20, and −2.10 (p = 0.001 vs placebo for baricitinib 4 mg and p = 0.037 for 8 mg), respectively. Mean changes for bone erosion were 0.90, 0.10, and 0.40 (p = 0.089 for 4 mg and p = 0.275 for 8 mg), respectively, in these treatment groups.Conclusion.MRI findings in this subgroup of patients suggest suppression of synovitis, osteitis, and combined inflammation by baricitinib 4 and 8 mg. This corroborates previously demonstrated clinical efficacy of baricitinib and increases confidence that baricitinib 4 mg could reduce the radiographic progression in phase III studies. [Clinical trial registration number (www.ClinicalTrials.gov): NCT01185353]

scholarly journals 278: The Impact of Hexvix Based Fluorescence Cystoscopy in Treatment Decisions of Bladder Cancer - Results of a Prospective Phase III Multicenter Study

2004 ◽  
Vol 171 (4S) ◽  
pp. 73-73 ◽  
Author(s):  
Christoph Durek ◽  
Sigrid Wagner ◽  
Bram Zeijlemaker ◽  
Jeroen Van Moorselaar ◽  
J. Alfred Witjes ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Multicenter Study ◽  
Treatment Decisions ◽  
Phase Iii ◽  
Fluorescence Cystoscopy ◽  
Prospective Phase ◽  
The Impact

scholarly journals 1021. HIV-1 RNA Blips and Low-Level Replication During Phase III/IIIb Cabotegravir + Rilpivirine Long-Acting Studies Are Similar to Oral 3-Drug Therapy and Not Associated with Week 48 Virologic Outcome

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S540-S541
Author(s):  
Christine L Talarico ◽  
Sterling Wu ◽  
Ojesh R Upadhyay ◽  
Marty St Clair ◽  
Veerle Van Eygen ◽  
...  
Keyword(s):  
Viral Load ◽  
Virologic Failure ◽  
Phase Iii ◽  
Individual Study ◽  
Treatment Groups ◽  
Qualitative And Quantitative ◽  
Low Level ◽  
Long Acting ◽  
Study Participants ◽  
Hiv 1

Abstract Background Phase III/IIIb studies demonstrated cabotegravir (CAB) + rilpivirine (RPV) long-acting (LA) dosed every 4 weeks (Q4W) was noninferior to current antiviral regimen (CAR) (FLAIR and ATLAS) and CAB + RPV LA dosed every 8 weeks (Q8W) was noninferior to Q4W (ATLAS-2M) through Week 48 (W48). HIV-1 ribonucleic acid (RNA) blips (viral load [VL] ≥50 to &lt; 200 c/mL) are common during antiretroviral therapy (ART) and generally not associated with subsequent virologic failure (2 consecutive HIV-1 RNA ≥200 c/mL). We compared the frequency of HIV-1 RNA blips and low-level qualitative and quantitative HIV-1 RNA replication among participants treated with CAB+RPV LA and oral CAR and assessed impact on virologic outcome. Methods Plasma samples collected at study visits were analyzed for HIV-1 RNA viral load using the Abbott RealTime HIV-1 assay and qualitative target detected (TD) or target not detected (TND) outcomes were provided for HIV-1 RNA &lt; 40 c/mL. The HIV-1 SuperLow assay (bioMONTR Labs) was used to measure HIV-1 RNA &lt; 2 c/mL at Baseline and W48. Results The proportion of participants with HIV-1 RNA blips was similar overall between Q4W CAB + RPV LA and CAR arms in FLAIR (38/283 [13%] vs 39/283 [14%]) and ATLAS (17/308 [6%] vs 23/308 [7%]). Presence of HIV-1 RNA blips in either arm was not associated with virologic non-response at W48 (HIV-1 RNA ≥50 c/mL per US Food and Drug Administration Snapshot). In ATLAS-2M, HIV-1 RNA blips were observed in 32/523 (6%; Q4W) and 18/522 (3%; Q8W) of participants, with W48 virologic nonresponse in 2 Q4W and 0 Q8W participants. TD outcomes at individual study visits were comparable between study arms for the 3 studies. At W48, the proportion of participants with HIV-1 RNA &lt; 2 c/mL was similar to Baseline and similar between treatment groups in all studies. Conclusion The proportions of study participants with HIV-1 RNA blips, TD viral load results, and HIV-1 &lt; 2 c/mL were similar between the Q4W and Q8W CAB+RPV LA and the oral 3-drug CAR arms through W48 in phase III/IIIb studies. HIV-1 RNA blips did not predict virologic nonresponse (Snapshot analysis) at W48. Disclosures Christine L. Talarico, M.S, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sterling Wu, PhD, GlaxoSmithKline (Employee, Shareholder) Marty St. Clair, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Veerle Van Eygen, MSc, Janssen Pharmaceutica NV (Employee) Krischan J. Hudson, PhD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sandy Griffith, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Conn M. Harrington, BA, ViiV Healthcare (Employee) Jan van Lunzen, MD, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) David Margolis, MD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) William Spreen, PharmD, ViiV Healthcare (Employee, Shareholder)

Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms

2018 ◽  
Vol 108 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Jaume Capdevila ◽  
Lisa Bodei ◽  
Philippa Davies ◽  
Vera Gorbounova ◽  
Robert T. Jensen ◽  
...  
Keyword(s):  
Treatment Options ◽  
Phase Iii ◽  
Neuroendocrine Neoplasms ◽  
Limited Evidence ◽  
Medical Needs ◽  
Phase Iii Clinical Trials ◽  
Metastatic Setting ◽  
Metastatic Lung ◽  
Prospective Phase ◽  
Unmet Medical Needs

Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.

Prognostic impact of recurrence score, endocrine response and clinical-pathological factors in high-risk luminal breast cancer: Results from the WSG-ADAPT HR+/HER2- chemotherapy trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 504-504
Author(s):  
Oleg Gluz ◽  
Ulrike Nitz ◽  
Matthias Christgen ◽  
Michael Braun ◽  
Kerstin Luedtke-Heckenkamp ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Recurrence Score ◽  
Phase Iii ◽  
Luminal Breast Cancer ◽  
Prognostic Impact ◽  
Treatment Intensification ◽  
Ki 67 ◽  
Prospective Phase ◽  
High Risk Cohort

504 Background: In HR+/HER2- N0-1 early BC, postmenopausal patients (pts) with RS™ > 25 and a substantial proportion of premenopausal pts seem to benefit from addition of adjuvant chemotherapy (CT) to endocrine therapy (ET). However, the magnitude of absolute benefit from this treatment intensification seems to depend on clinical-pathological and biological prognostic factors. For the first time, we present outcome from the CT part of the prospective phase III WSG-ADAPT HR+/HER- trial combining both static (RS in baseline core biopsy (CB) and dynamic (Ki67 response) biomarkers to optimize adjuvant therapy in luminal EBC. Methods: Pts with clinically high-risk HR+/HER2- EBC (cT2-4 OR clinically N+ OR G3 OR Ki67>15%) were initially treated by 3 (+/-1) weeks of standard ET (postmenopausal: mostly AI; premenopausal: TAM) before surgery or sequential CB. Pts with cN2-3 or G3/Ki67>40% were randomized directly to the CT trial. pN0-1 pts with RS0-11 OR RS12-25/ET-response (central Ki67postendocrine<10%) received ET alone; the remaining high-risk cohort was randomized to the CT trial: (neo)adjuvant dose-dense CT (4xPaclitaxelà4xEC q2w vs. 8xNab-Paclitaxel q1wà4xEC q2w) followed by ET. Primary endpoint is efficacy comparison of CT schedules for survival; secondary endpoints reported here involve impacts of key prognostic factors on survival. Kaplan-Meier and Cox proportional hazard models were used to estimate survival curves and hazard ratios. For this analysis, subgroups free of selection bias by RS/ET-response were defined. Results: 5625 pts were screened and 4621 (ITT) entered the trial. After 4.9y median follow-up, higher baseline and post-endocrine Ki-67 levels were associated with poorer iDFS (both p < 0.001). In the CT cohort (n = 2331), higher RS, nodal status, and tumor size were generally associated with poorer iDFS. However, iDFS differed between N1 and N0 status only among younger pts (<50 years). In pts with >4 positive LN (n = 390), lower RS was associated with improved iDFS (RS0-11 vs RS > 25: plog-rank= 0.016, 5y-iDFS 90% vs. 64%). In pts with RS > 25 (n = 965), low Ki67postendocrine, N0 status, and c/pT1 status were associated with improved iDFS. In particular, ET-responders had higher 5y-iDFS (84%) than ET-non-responders (77%; plog-rank= 0.040). Younger patients (<50 years old) with N0-1 RS 12-25/ ET-non-responders treated by CT had non-significantly poorer 5-year iDFS (89%) compared to those with ET-response treated by ET only (92%) (plog-rank= 0.249). Conclusion: First results from the prospective high risk cohort from a large prospective phase III ADAPT trial provide evidence for good prognosis in some pts with >4 positive LN and e.g. low RS. Moreover combination of lower post-endocrine Ki-67 and limited tumor burden may be a promising criterion for CT de-escalation strategies even in patients with high RS. Clinical trial information: NCT01779206.

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