A population-based study evaluating metastatic renal cell cancer (mRCC) patients treated with interferon (IFN) alone, first-line IFN then second-line sunitinib, or sunitinib alone

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15572-15572 ◽  
Author(s):  
C. K. Kollmannsberger ◽  
D. Y. Heng ◽  
N. Murray ◽  
K. N. Chi
Keyword(s):  
Overall Survival ◽  
Standard Treatment ◽  
Population Based ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Group A ◽  
Group B ◽  
The Impact

15572 Background: Previously, immunotherapy agents such as IFN were the only treatments available for mRCC. Sunitinib has demonstrated prolonged progression free survival in a phase III trial but overall survival benefit has yet to be determined and few patients (pts) with poor MSKCC prognostic profiles were included. Methods: The province-wide BC Cancer Agency Registry was cross-referenced to the central pharmacy database to identify all pts with the diagnosis of mRCC who were treated with IFN and/or sunitinib. Sunitinib became available after October 2005 under an expanded access program or as standard treatment. Three groups of pts were identified: Group A consisted of pts who received IFN alone between January 2003 to October 2005, Group B was all pts who progressed on first-line IFN after October 2005 and subsequently were treated with second-line sunitinib and Group C was all pts treated with first-line sunitinib. Baseline characteristics and overall survival were collected on all patients. Results: A total of 75 patients were identified with 36 patients in Group A, 23 patients in Group B, and 16 patients in Group C. Data are reported from the initiation of IFN in Group A and the initiation of sunitinib in Groups B and C. Median follow-up was 6.0 months in group A, 7.6 months in group B, and 6.2 months in group C. Median age of treatment initiation (62y vs. 60y vs. 62y), number of metastatic sites (>1 site in 63% vs. 61% vs. 56%), and Karnofsky performance status (79 vs. 86 vs. 81) were similar between groups A, B and C, respectively. The MSKCC prognostic profiles were favorable, intermediate and poor in 26%, 51% and 23% in group A, 17%, 65% and 17% in group B and 31%, 38% and 31% in group C, respectively. The estimated 6-month overall survival in groups A, B and C was 56%, 72% and 100%, respectively (log rank A vs C p=0.009; log rank B vs C p=0.042). Conclusion: With the limitations of retrospective analysis and preliminary follow-up, the introduction of sunitinib as standard treatment into the general population of patients with mRCC appears to be associated with a longer overall survival compared to patients treated with IFN alone. Population-based analysis on the impact of the introduction of sunitinib therapy is ongoing. No significant financial relationships to disclose.

Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial

2014 ◽  
Vol 32 (23) ◽  
pp. 2423-2429 ◽  
Author(s):  
Helmut Oettle ◽  
Hanno Riess ◽  
Jens M. Stieler ◽  
Gerhard Heil ◽  
Ingo Schwaner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Folinic Acid ◽  
Karnofsky Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Gemcitabine Refractory

Purpose To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid–modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy. Patients and Methods A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status. Results Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001). Conclusion Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.

scholarly journals Integration of CTA in the Diagnostic Workup of New Onset Chest Pain in Clinical Practice

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Nazario Carrabba ◽  
Martina Berteotti ◽  
Giulia Taborchi ◽  
Francesca Ciatti ◽  
Manlio Acquafresca ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Chest Pain ◽  
Diagnostic Workup ◽  
Second Line ◽  
Functional Tests ◽  
First Line ◽  
Group A ◽  
Group B ◽  
The Impact ◽  
New Onset

Background. Recently, NICE guidelines recommend the use of computed tomographic angiography (CTA) as the first line of investigation for new onset chest pain. We sought to evaluate the impact of the integration of CTA in the diagnostic workup, as either a first- or second-line of investigation, in the clinical practice for patients presenting with new onset chest pain, with suspicion that it may be due to coronary artery disease (CAD). Method and Results. From 2014 to 2016, 208 outpatients (mean age 63.8 ± 12.7, 37% female) with an unknown CAD diagnosis were evaluated. About half (n=106, 51%) received usual testing care plus CTA as a second-line investigation (group A), while the other half (n=102, 49%) received CTA as a first-line investigation (group B). Care decisions and test interpretations were made by the attending physician. Obstructive CAD (O-CAD) was defined as >50% stenosis in the principal branch. As determined by CTA, the rates of CAD in group A vs. group B were the following (P=0.001): 31.1% vs. 27.4% for normal/minimal CAD; 42.5% vs. 63.7% for no O-CAD; and 26.4% vs. 8.8% with O-CAD. Based on a diagnostic result of no O-CAD, invasive angiography was cancelled in 42.6% (n=45) of group A patients, and additional functional tests were cancelled for the same reason in 63.7% (n=65) of group B patients, without adverse events at median 3-year. The average diagnostic cost for patients in our study was lower in group B (206 vs. 324.42 euro; P<0.0001). Conclusions. In clinical practice, CTA, as a first- or second-line investigation, most commonly detected no O-CAD in new onset chest pain patients, leading us to safely avoid unnecessary ICA or additional functional tests. The use of CTA as a first-line investigation also appears to be cost saving, but its cost-effectiveness remains to be demonstrated in larger studies.

A randomized phase II factorial design trial of CPT-11 versus PTX versus each combination with S-1 in patients with advanced gastric cancer refractory to S-1: Final results of OGSG0701.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 117-117 ◽  
Author(s):  
Kazuhiro Nishikawa ◽  
Hiroshi Imamura ◽  
Tomono Kawase ◽  
Masahiro Gotoh ◽  
Yutaka Kimura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Progression Free Survival ◽  
Correct Selection ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Group A ◽  
Group B

117 Background: S1 + platinum (SP) is recognized as standard first-line chemotherapy for advanced gastric cancer(AGC), and S1 monotherapy is suggested for frail AGC patients or adjuvant setting in Japan. However, taxane or CPT-11 were often employed as second-line treatment for the patients who were resistant to S1-containing regimen. A retrospective analysis has reported that S1 combination chemotherapy extended overall survival as second-line treatment for AGC. Methods: Patients with AGC who confirmed disease progression by imaging after the first-line therapy with S1 or SP were randomized in four groups; CPT-11 150 mg/m2, day1, q2w (Group A), PTX 80 mg/m2, day1, 8,15, q4w (Group B), CPT-11 80 mg/m2, day1, 15, S-1 80 mg/m2, day1-21, q5w (Group C1), PTX 50 mg/m2,day1, 8, S1 80 mg/m2, day1-14, q3w (Group C2). Primary endpoint was overall survival (OS), and secondary endpoints were progression free survival (PFS), overall response rate (ORR) and safety. Sample size was set at 100 to 120 to achieve 2 months improvement of OS by using CPT-11 or by adding S1 with approximately 80% probability of the correct selection. Results: From July 2008 to March 2012, 127 patients were enrolled. The OS was 11.3/11.3/14.6/10.5 months(M) (Group A/B/C1/C2), 11.8M in Group A+C1 and 11.1M in Group B+C2 (p=0.922, HR: 0.981 [0.679-1.419]), 11.3M in Group A+B and 11.1M in Group C1+C2 (p=0.808, HR: 0.952 [0.643-1.412]), respectively. The PFS was 3.0/4.4/3.8/3.5M (Group A/B/C1/C2), 3.6M in Group A+C1 and 4.1M in Group B+C2 (p=0.035, HR:0.674 [0.468-0.972]) 3.7M in Group A+B and 3.7M in Group C1+C2 (p=0.931, HR: 1.017 [0.643-1.412]). The ORR was 7.1/16.3/4.5/5.0% (Group A/B/C1/C2), 4.7%[1.7-15.2] in Group A+C1 and 12.7%[5.6-23.5] in Group B+C2 (p=0.241), 11.8%[5.8-20.6] in Group A+B and 4.6%[0.6-16.2] in Group C1+C2 (p=0.572).Major Grade 3/4 toxicity (Group A/B/C1/C2, %), was leukopenia (12/7/5/0), neutropenia (29/16/24/24), nausea (7/2/10/5), diarrhea (5/0/10/0), and fatigue (5/2/10/5). Conclusions: From our results, we do not recommend consecutive use of S1 but CPT-11 or PTX monotherapy as second-line treatment in AGC refractory to S1 or SP. Clinical trial information: 000000677.

Updated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7521-7521 ◽  
Author(s):  
Tetsuya Mitsudomi ◽  
Satoshi Morita ◽  
Yasushi Yatabe ◽  
Shunichi Negoro ◽  
Isamu Okamoto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Significant Difference ◽  
The Impact ◽  
Egfr Tki ◽  
First Line Treatment ◽  
Platinum Doublet

7521 Background: WJTOG3405 met its primary endpoint of progression free survival (PFS) (9.2 months (mo.) for G vs. 6.3 mo. for CD, hazard ratio (HR) 0.489, 95% confidence interval (CI): 0.336-0.710). (Mitsudomi et al., Lancet Oncol., 2010). However, the impact on overall survival (OS) was not clear then because of relatively short follow-up period. Methods: Overall survival (OS) was re-evaluated using updated data (data cutoff, 31 July, 2011, median follow-up, 34 months) for 172 patients. Results: Eighty-two events had occurred (48%). Median survival time (MST) for G arm was 36 mo. (95% CI: 26.3 -) which was not significantly different from 39 mo. (95% CI: 31.2 -) for CD arm (HR 1.185, 95% CI 0.767-1.829). Multivariate analysis using Cox proportional hazards model revealed that none of covariates (treatment arm, smoking status, sex, age, postoperative recurrence or IIIB/IV, and mutation type) significantly affected OS. In the G arm, MST of patients with exon 19 deletion (36 mo.) was comparable to that of patients with L858R (35 mo.). In the CD arm, 78 patients (91%) received EGFR-TKI as the 2nd or later line treatment, whereas in the G arm, 52 patients (61%) received platinum doublet. Accordingly, 130 patients received both platinum doublet and EGFR-tyrosine kinase inhibitor (TKI) and 34 patients received EGFR-TKI without platinum doublet in their whole courses of therapy. MST for the former and the latter group were 36 months (95% CI: 31.2-45.7) and 45 months (95% CI: 25.6-), without significant difference. Conclusions: This update OS analysis revealed that G for advanced NSCLC with EGFR mutation offers distinct survival benefit of 3 years. There was no difference in OS whether the first-line treatment was G or CD, in accordance with the precedent studies. The reason why PFS difference was not translated into OS difference is probably due to high cross over rate to EGFR-TKI. However, it was noteworthy that 40% of patients in the G arm could be managed without platinum doublet and yet had similar outcome.

scholarly journals Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner
Keyword(s):  
Systemic Treatment ◽  
Sequential Treatment ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Curative Surgery ◽  
To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

scholarly journals DERN CONTROL POINT INHIBITORS AND THEIR POSSIBILITIES FOR THE THERAPY OF METASTATIC UROTELIAL CANCER

2020 ◽  
Vol 6 (5(74)) ◽  
pp. 4-8
Author(s):  
M.N. Tillyashajhov ◽  
S.V. Kamyshov ◽  
E.V. Bojko
Keyword(s):  
Overall Survival ◽  
Control Point ◽  
Surface Protein ◽  
New Drugs ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Critical Question ◽  
Accelerated Approval ◽  
New Biomarkers

For a long time, chemotherapy remained the main treatment option for metastatic urothelial carcinoma (mUC). Over the past year, there have been revolutionary changes associated with the approval of five new drugs aimed at blocking the interaction between the surface protein of T‑lymphocytes PD‑1 and its ligands PD‑L1 and PD‑L2, resulting in the activation of the immune response. It is noteworthy that the anti‑PD‑1 antibody pembrolizumab demonstrated an increase in overall survival relative to chemotherapy in a randomized phase III trial in the second line with mUC. Based on this level 1 evidence pembrolizumab was approved by the US Food and Drug Administration (FDA). Nivolumab (antibody PD‑1) also demonstrated an increase in overall survival compared to historical control and was approved by FDA. Likewise, antibodies targeting PD‑L1, including atezolizumab, durvalumab and avelumab, received accelerated approval from the FDA as the second line of treatment for mUC. Some of these agents are approved in the first line by the results of phase II study (atezolizumab and pembolizumab received accelerated approval for first‑line treatment in patients not receiving cisplatin). Despite these many endorsements, clinical development of new biomarkers for selection of patients, who can get maximum advantages of immunotherapy and also for development the optimal therapy sequencing still are biggest and critical question for future investigation.The clinical introduction of biomarkers to determine optimal treatment of patients remains extremely important.

Gallium scans in the evaluation of residual masses after chemotherapy for seminoma.

1995 ◽  
Vol 13 (11) ◽  
pp. 2784-2788 ◽  
Author(s):  
G P Warren ◽  
L H Einhorn
Keyword(s):  
False Negative ◽  
Fibrous Tissue ◽  
Salvage Chemotherapy ◽  
First Line ◽  
Chemotherapy Group ◽  
Computed Tomographic ◽  
Group A ◽  
Residual Masses ◽  
Group B

PURPOSE To assess the ability of gallium scans to determine whether residual masses consist of viable tumor or necrotic fibrous tissue after chemotherapy for seminoma. PATIENTS AND METHODS Thirty-two patients were enrolled and 27 were assessable. Patients receiving first-line or salvage chemotherapy had gallium scans performed during their first and last scheduled course of chemotherapy and results were compared with restaging computed tomographic (CT) scans and subsequent clinical outcome. RESULTS Of 27 assessable patients, 22 received first-line chemotherapy (group A) and five salvage chemotherapy (group B). Eight patients were not gallium-avid before chemotherapy despite obvious clinical and radiographic evidence of metastatic seminoma. Eighteen of 19 gallium-positive patients had a persistent mass postchemotherapy on abdominal CT. Of 16 patients in group A whose tumors were gallium-avid, all 16 had normalized gallium scans after chemotherapy. However, two of these 16 patients recurred in their original disease site. In group B, there were three patients with gallium-avid tumors and all three had normalized scans postchemotherapy. Two patients who were not gallium-avid (one each in group A and B) also developed recurrent disease. Twenty-four of 27 patients are alive with no evidence of active disease at a median follow-up time of 18 months, including 20 with more than 1 year of follow-up data. CONCLUSION Eight of 27 patients had false-negative gallium scans at the time of diagnosis. All nineteen gallium scans that were initially positive reverted to normal after chemotherapy. Two of 19 patients' follow-up gallium scans were false-negative. We therefore feel that gallium scans have minimal value in the prechemotherapy or postchemotherapy evaluation of metastatic seminoma.

Patterns of Disease Relapse and Progression in Patients with Multiple Myeloma After First Line Therapy with Autologous Stem Cell Transplantation: Implications for Patient Monitoring After Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 825-825
Author(s):  
Dmitriy Zamarin ◽  
Manisha Bhutani ◽  
Danielle Chimento ◽  
Sergio Giralt ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Soft Tissue ◽  
First Line ◽  
Post Transplant ◽  
First Line Therapy ◽  
Line Therapy ◽  
Group A ◽  
One Year ◽  
Group B

Abstract Abstract 825 BACKGROUND: Autologous stem cell transplantation (ASCT) is a widely used therapeutic option in first line treatment of multiple myeloma (MM). However, many patients eventually relapse. While precise knowledge of relapse and progression (R/PD) patterns would be important to generate evidence based surveillance recommendations after ASCT, such data is limited in the literature, especially in the era following the introduction of the free light chain assay. The purpose of this study is to examine the patterns of post-ASCT relapse and to derive evidence based recommendations for optimal surveillance of patients. METHODS: We performed a retrospective analysis on 258 patients with MM who underwent ASCT within one year of diagnosis at MSKCC between 2000 and 2010, as part of first line therapy. We used the IMWG standard criteria for serologic and clinical R/PD. We first determined for all patients the date of serologic R/PD. Patients identified as having serologic R/PD were further examined to determine whether clinical (anemia, renal failure, hypercalcemia, development of soft tissue lesions), radiologic (skeletal survey) or urinary R/PD had anteceded serologic R/PD. Several groups of patients were derived and further analyzed in terms of relapse patterns and adequacy of follow up. RESULTS: Among 258 patients, 173 were determined to have serologic R/PD at a median of 19.2 months post-transplant. Among these patients, on the dates of their serologic R/PD, 17 (9.8%) had concurrent overt symptomatic evidence of clinical/radiologic R/PD (Group A symptomatic R/PD), while 156 (90.2%) were found to have isolated asymptomatic serologic R/PD without apparent evidence of concomitant clinical/radiologic R/PD (Group B asymptomatic R/PD). Group A included patients with distinct and sometimes coinciding clinical characteristics (poor risk cytogenetics with aggressive disease (n=3), leptomeningeal relapse (n=1), soft tissue relapse (n=4) and acute severe anemia at relapse (n=3)); patients with IgA gammopathy (n=5); and patients considered to have inadequate serologic follow up intervals (range of follow up interval between date of serologic R/PD and prior serologic testing 149 to 245 days) (n=6). Upon further examination of group B, 44 patients had radiologic imaging at the time of serologic R/PD (within 4 weeks following the date of serologic R/PD). Fourteen among them (32%) had evidence of new bone lesions. Among all 173 patients with serologic R/PD, 83 patients had a skeletal survey within one year prior to the date of serologic R/PD. Only 3 (3.6%) had evidence of radiologic R/PD anteceding serologic R/PD. All 3 patients were considered to have had inadequate serologic follow up interval (Range 208 to 252 days). Abnormal urine immunofixation (UIF) anteceded serologic R/PD in 5 out of 41 (12%) patients tested who had achieved CR post transplant. In these patients the abnormal UIF anteceded the serologic R/PD by a mean of 2.4 months. Abnormal UPEP anteceded serologic R/PD by 1.9 months in only 1 out of 40 (2.5%) patients tested who had achieved less than CR post transplant. CONCLUSIONS: Based on the results of this analysis, several conclusions can be drawn: 1) The vast majority of R/PD in patients with MM are asymptomatic R/PD detected first by serologic studies. A small percentage of patients (those with aggressive cytogenetics, specific relapse types including soft tissue, severe cytopenia, and IgA gammopathy) will have symptomatic R/PD with overt concomitant evidence of clinical and/or radiologic R/PD at the time of serologic R/PD; 2) Among patients who have apparent asymptomatic R/PD, a significant percentage will have evidence of skeletal lesions and therefore imaging should be recommended in these patients; 3) In the absence of serological R/PD, routine surveillance screening with yearly skeletal surveys cannot be recommended based on this analysis since this test was not useful in any of the analyzable patients in whom it was obtained; 4) Aside from few patients in CR whose relapse may be detected earlier by UIF (with probably no clinical benefit), all patients with multiple myeloma whose disease progresses will have serologic R/PD at the time of progression and follow up limited to serologic testing may well be sufficient for monitoring patients with MM post transplant. Disclosures: No relevant conflicts of interest to declare.

Patient Outcomes with Proteosome Inhibitor Bortezomib in Multiple Myeloma at an English District General Hospital

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5745-5745
Author(s):  
Anil Vaikunth Kamat ◽  
Tariq Shafi ◽  
Raphael A. Ezekwesili
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Second Primary ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Second Primary Malignancies

Abstract Bortezomib is a targeted proteosome inhibitor licensed & approved for in multiple myeloma both as first line and in relapsed setting. This is a retrospective non experimental cross sectional quantitative comparative group study using clinical case notes, laboratory & pharmacy records for patients treated with Bortezomib in 2011 & 2012. Outcomes studied included remission status, adverse events, progression free survival and overall survival at follow up. The study also looked at the comparative responses of cohort of patients administered Bortezomib through intravenous & subcutaneous route. The cohort consisted of 33 patients, 21 male, 11 female, median age 71 years, first line 10 patients, second line 23 , median number of cycles in 2011 & 2012 – first line 3 & 8 , second line 5 & 4, respectively. In 2011, 8 received intravenous treatment, 9 were switched from intravenous to subcutaneous route whilst all patients from 2012 received subcutaneous Bortezomib. The most frequently used regimen was Bortezomib Dexamethasone ( VD). The overall response rate ( ORR >/= Minor Response) was: First line 70% (7/10) ; Second line 47.8% ( 11/23); median PFS ( Figure 1) 6 months ( First line: 7 months ; Second line : 6 months) and median overall survival ( Figure 2) at follow up: 9 months ; 39.4 % ( 13/33) First line 8.5 months, Second line 11 months. Subcutaneous Bortezomib was equivalent to intravenous Bortezomib in terms of efficacy & tolerance. Of 33 patients, there were 12 dose reductions. Adverse events reported included: peripheral Neuropathy - grade 3 - 6% ( all grades 27.3%); Diarrhoea - grade 3 - 3% (all grades 6%); Nausea / Vomiting - grade 3 - 3% ( all grades 6%) and Second Primary Malignancies - 12% ( 4 of 33). Mortality at follow up was 20 patients from cohort of 33 ; causes included disease progression in 11, second primary malignancy with disease progression in 4, COPD 2, Systemic Amyloidosis 2, Tuberculosis 1 , Multiple co morbidities 1 and Asthma with mechanical failure in single patient. Second primary malignancies ( 4/33) included Prostate carcinoma ( 1), Renal Cell Carcinoma (1), Neuroendocrine tumour ( 1 ) and Unknown Primary in single patient. Beyond second line treatment, majority (14 of 23 patients; 60.9 %) did not have further active treatment. These data indicate that patient outcomes were modest compared to published data from VISTA and APEX trials. Majority of patients did not have further active treatment beyond second line which suggests the most effective treatment strategy should be used upfront as patients may not be fit to have further lines of therapy despite availability of recently introduced novel targeted agents. A higher percentage of second primary malignancies were noticed in this cohort which should be an area of further clinical research. Figure 1: Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 1:. Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 2: Overall survival with Bortezomib as first line & second line in multiple myeloma Figure 2:. Overall survival with Bortezomib as first line & second line in multiple myeloma Disclosures No relevant conflicts of interest to declare.

Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
E. Van Cutsem ◽  
M. Nowacki ◽  
I. Lang ◽  
S. Cascinu ◽  
I. Shchepotin ◽  
...  
Keyword(s):  
Response Rate ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Skin Reactions ◽  
Group A ◽  
Group B ◽  
First Line Treatment

4000 Background: Cetuximab in combination with irinotecan-based regimens has proven activity in previously-treated patients (pts) with mCRC. The present trial investigated the effectiveness of cetuximab in combination with standard FOLFIRI compared with FOLFIRI alone in the first-line treatment of pts with epidermal growth factor receptor (EGFR)-expressing mCRC. Methods: Pts were randomized 1:1 to receive either cetuximab (400 mg/m2 initial dose then 250 mg/m2/week [w]) plus FOLFIRI q 2 w (irinotecan 180 mg/m2, FA 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 hours) (Group A) or FOLFIRI alone (Group B). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate (RR), disease control rate and safety. 633 events were required to statistically differentiate PFS between groups with 80% power. Results: Between August 2004 and October 2005, 1,217 pts were randomized, 608 to Group A and 609 to Group B (60% male, median age 61 [19–84], ECOG performance status: 0=54%; 1=43.5%; 2=3.5%). Median PFS was significantly longer for Group A compared to Group B (8,9 months [8 - 9,5] for Group A vs. 8 months [7.6 - 9] for Group B, p=0.036). Response Rate was also significantly increased by cetuximab (46.9% vs. 38.7%, p=0.005). Treatment was generally well tolerated with neutropenia (26.7% Group A, 23.3% Group B), diarrhea (15.2% and 10.5% respectively) and skin reactions (18.7% and 0.2% respectively) being the most common grade 3/4 adverse events. Conclusions: Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone. [Table: see text]

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