Sequential therapy with sorafenib and sunitinib in renal cell carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5106-5106 ◽  
Author(s):  
A. Dham ◽  
A. Z. Dudek
Keyword(s):  
Renal Cell Carcinoma ◽  
Disease Progression ◽  
Median Duration ◽  
Stable Disease ◽  
Response To Treatment ◽  
Second Line ◽  
Line Therapy ◽  
Group A ◽  
Group B

5106 Background: Sunitinib and sorafenib are two small-molecule tyrosine kinase inhibitors (TKI) that have been shown to have antitumor activity in advanced renal cell carcinoma (RCC). However, the optimal sequence of first- and second-line therapies with sunitinib and sorafenib is still unclear. The purpose of this study was to assess whether an objective disease response could be identified in patients after receiving sequential treatment with these two agents. Methods: Patients who had progressed or experienced unacceptable toxicity after first-line therapy with either sunitinib or sorafenib and then subsequently received second-line therapy with the other TKI agent were evaluated for their response to sequential treatment using RECIST criteria. Results: Thirty-seven patients were identified (29 male and 8 female) with a median age of 62 years (range 32–75). Twenty-three patients received sorafenib followed by sunitinib (Group A), and 14 patients received sunitinib followed by sorafenib (Group B). According to Memorial Sloan-Kettering prognostic model, 35% of patients in Group A had favorable risk, 52% had intermediate and 13% had poor risk, whereas 50% of patients in Group B had favorable risk, 43% had intermediate and 7% had poor risk. Three patients (13%) in Group A and two (14%) in Group B switched TKI due to toxicity, while all remaining patients switched due to disease progression. For patients in Group A, median duration of stable disease after starting sunitinib was 32 weeks (range 6–37 weeks)(median follow up 266 days); 9% were not evaluable for response to treatment; 34% had disease progression; and four patients (17%) had an objective partial response of 31%, 36%, 27% and 50%, respectively. For patients in Group B, median duration of stable disease after starting sorafenib was 8 weeks (range 4–10 weeks) (median follow up 179 days); 7% were not evaluable for response to treatment; 50% had disease progression; and one patient (7%) had no evidence of disease after tumor resection. The median duration of disease control in Groups A and B was 42 weeks (range: 10–113 wks) and 30.5 weeks (range: 4–56 wks), respectively. Conclusions: While disease control was observed in both sequences, the duration of response was longer in patients receiving sorafenib followed by sunitinib. [Table: see text]

Efficacy of Cyclosporine Treatment in Patients with MDS.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4608-4608
Author(s):  
Alina Kokhno ◽  
Elena Parovitchnikova ◽  
Elena Mikhailova ◽  
Yulia Olshanskaya ◽  
Irina Kaplanskaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stable Disease ◽  
Response Rate ◽  
Bone Marrow Failure ◽  
Normal Karyotype ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Myelodysplastic syndrome (MDS) represents a heterogenous group of myeloid neoplasms characterized by abnormal differentiation and maturation of myeloid cells, bone marrow failure and genetic instability. The recent clinical and laboratory investigations suggest that MDS is closely related to diseases in which the bone marrow failure is mediated at least in part by the immune system. The are few studies concerning the of efficacy of treatment of MDS pts with cyclosporine A (CSA) but they are limited to the group of pts with bone marrow hypoplasia. The aim of our study was to evaluate the efficacy of CSA treatment in MDS pts as first line or second line therapy. 48 pts with different forms of MDS were included in study. The group of first line CSA treatment included 30 pts, male-18/female-12, RA-3, RARS-1, RCMD-18, RAEB-7, RAEBt-1, 20-normal karyotype, 10-different abberations including: 5q−, 16q+, −7, 12q+, −Y, [11p+,7q−] and complex abb. Hypoplastic bone marrow was revealed in 15 pts, hyperplastic-8 pts, hypo/hyper-7 pts. Second line therapy group included 18 pts, male-9/female-9, RCMD-11, RARS-1, RAEB-5, RAEBt-1, normal karyotype-3, cytogenetic anomalies-13 (+8, 5q−,−7, +8 and complex abb.). Hypoplastic bone marrow was revealed in 12 pts, hyperplastic-4 pts, hypo/hyper-4 pts. The first line therapy consited of splenectomy in 8 pts, low doses of Ara-C-3, interferon-α-3, chemotherapy-2 and ATG-2 pts. CSA was applied at 5–10 mg/kg/day initially and then adjusted according to blood levels and toxicity. The maintenance dose was 1–3 mg/kg/day. Minimum time to response evaluation was one month. Complete response (CR) was defined as normal PB counts, BM aspirate; partial response-improvement of PB counts to 50% of normal and freedom from transfusions; stabilization-decrease of transfusion requirements and stabilization of PB counts for more then 1 month. Total response rate in first group was 60% (18 pts) with median follow up of 10 months (2–134). CR was estimated in 20% (6pts), median follow-up 72 months (44–134). 2 pts with CR are in clonal remission. 2 pts from response group developed acute leukemia (AL). 40% of pts showed no response.58% of pts without response developed RAEB or AL. 42% of pts were in stable disease and were treated with another modalities. The response rate in second group was 61% (11 pts) with median follow-up of 7 months (1–78). 22% (4 pts) achieved CR, median follow-up 60 months (43–78). 39% of pts showed no response. 71% from these pts (5) transformed to RAEB or AL. 2 pts remained in stable disease. In both groups response was registrated from 1 to 4 months from treatment initiation (median 3 months). CR was achieved in the majority of pts after 1 year of treatment. Response was achieved in 77% of pts with hypo/hyper and hypoplastic bone marrow and in 12% of pts with hyperplastic bone marrow. Overall survival was decreased in pts with more the 5% blasts in bone marrow (p=0,02 for 1st line group, p=0,075 for 2nd line group), and increased for pts with hypo and hypo/hyper bone marrow cellularity (p=0,002 for 1st line group). There was no impact of cytogenetics. We may conclude, that CSA demonstrates good efficacy in therapy of MDS pts, especially for pts with RA, RARS and RCMD with hypo and hypo/hypercellular bone marrow and reactive lymphoid nodules in bone marrow. It can be initiated as 1st or 2nd line therapy and should be continued at least for 3 months before evaluating of response.

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.

Clinical outcome of patients with metastatic renal cell carcinoma who interrupted VEGFR-TKI after achieving stable disease or better response.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 459-459
Author(s):  
Dong Hoe Koo ◽  
Inkeun Park ◽  
Jae-Lyun Lee ◽  
Jin-Hee Ahn ◽  
Dae Ho Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Outcome ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Stable Disease ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Free Survival

459 Background: The purpose of the this study is to evaluate the clinical outcome of VEGFR-TKIs interruption in patients with metastatic renal cell carcinoma (mRCC) after achieving stable disease (SD) or better response. Methods: A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with VEGFR-TKIs between January 2008 and July 2014 (n=505). Patients who achieved SD or better response under VEGFR-TKI and later discontinued VEGFR-TKIs for any reason with the exception of disease progression were included in the analysis. Outcomes analyzed were progression free survival (PFS) after VEGFR-TKIs discontinuation, patterns of disease progression, time to subsequent therapy (TST), response to VEGFR-TKI resumption, and time to treatment failure (TTF) after TKI resumption. Results: We identified 32 patients (sunitinib=20, sorafenib=7, and pazopanib=5). The responses to VEGFR-TKIs were CR (n=4), PR (n=11), SD (n=15), and controlled but non-measurable (n=2). Median time to interruption from the initiation of VEGFR-TKI therapy was 16.6 months (95% CI, 12.8-20.3). The main causes of VEGFR-TKI interruption was toxicity (n=19, 59.4%), will to have treatment holiday (n=7, 21.8%), patient’s refusal (n=3, 9.4%), and others (n=3, 9.4%). At the time of analysis, 16 patients had disease progression and 1 patient was dead. With a median follow-up duration of 56.6 months (range, 12.6-167.4), median PFS from VEGFR-TKI interruption was 23.8 months (95% CI, 12.5-35.0), and the median TST was 26.2 months (95% CI, 15.9-36.6). The progression was observed in pre-existing lesions in 7 patients (43.7%) or new lesions developed in 9 (56.3%). Among 11 patients who received VEGFR-TKI resumption, 2 patients (18.2%) achieved a PR and the stable disease was observed in 9 (81.8%) with a median TTF of VEGFR-TKI resumption of 6.2 months (95% CI, 4.0-8.4). Conclusions: In patients with mRCC controlled with VEGFR-TKIs, VEGFR-TKI could be interrupted at least temporarily when clinically warranted.

scholarly journals Survival Improvement in the Last 45 Years in Patients with Multiple Myeloma: Real-World Data from a Single Center

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5573-5573
Author(s):  
Luis Gerardo Rodríguez-Lobato ◽  
Carlos Fernández De Larrea ◽  
Natalia Tovar ◽  
Maria Teresa Cibeira ◽  
Joan Bladé ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Infectious Complications ◽  
Early Mortality ◽  
Line Treatment ◽  
Second Line ◽  
Single Institution ◽  
Group A ◽  
Group B ◽  
Stratified Analysis

Abstract INTRODUCTION: Multiple myeloma (MM) is the second most common blood cancer, with estimated 5-year overall survival (OS) rate of 50%. Survival rates have steadily increased over last decades due to the introduction of high-dose melphalan with autologous stem cell transplantation (ASCT) and newer drugs (thalidomide, lenalidomide and bortezomib). Nevertheless, most studies in MM do not reflect the true real-world population. The aims of the present study were to analyze the survival outcomes, as well as to determine the incidence and causes of early mortality and time to next therapy (TTNT) over time, in patients diagnosed with MM, treated and followed at a single institution. METHODS: We reviewed the clinical records of patients with MM diagnosed at a single institution from January 1970 to December 2015. One thousand one hundred sixty-one patients (591 [50.9%] male; median age at diagnosis 64 years) was the final study population. Median follow-up for alive patients was 5.4 years (range, 0.5-34.4 years). The diagnosis of MM was based on international criteria established during the different periods analyzed. Baseline demographics, clinical and laboratory data, treatment and follow-up were collected. The population was divided into three periods, which included: group A (1970 to 1985), group B (1986 to 1999) and group C (2000 to 2015) (Table 1). The Ethics Committee of the Hospital Clínic of Barcelona approved the study. RESULTS: The median OS (mOS) of all patients was 3.6 years (95% CI: 3.2-3.8). We observed an improvement in mOS during follow-up (Group A: 1.7 years [95% CI: 1.23-2.06]; Group B: 2.92 years [95% CI: 2.44-3.32]; Group C: 5.01 years [95% CI: 4.31-5.52]; p<0.00001). The 5-year OS were 21%, 32% and 50%, respectively (Figure 1A). These findings were maintained in the stratified analysis according to 3 periods by age: < 65 years old (Group A: 1.9 years [95% CI: 1.19-2.54]; Group B: 3.6 years [95% CI: 3.14-4.92]; Group C: 7.5 years [95% CI: 5.64-9.79]; p<0.00001); 65-75 years old (Group A: 1.5 years [95% CI: 0.86-2.26]; Group B: 2.3 years [95% CI: 1.91-2.96]; Group C: 4.3 years [95% CI 3.8-5.25]; p<0.00001); and >75 years old (Group A: 1.1 years [95% CI: 0.12-2.13]; Group B: 1.8 years [95% CI: 1.30-2.74]; Group C: 2.8 years [95% CI: 1.99-3.24]; p<0.001) (Figure 1B to 1D). In the multivariate Cox proportional hazard model, these periods of time retained its independent prognostic value in terms of OS (Group B: HR=0.66; 95% CI 0.55-0.79; p<0.0001; Group C: HR=0.39; 95% CI 0.32-0.47; p<0.00001; compared with Group A). The early mortality rate (first 60 days after diagnosis) was 5.7%; 17.1% in the Group A, 5.7% in Group B, and 2.7% in Group C; p<0.001. The most frequent causes of early mortality were disease-related (46.7%, 63.6% and 66.6%; respectively), and infectious complications (36.7%, 22.7%, and 20.0%; respectively). In terms of time elapse between the start of front-line treatment until the beginning of the subsequent line, the median time to second line treatment in the group A, B and C, were 10.5 months (95% CI: 8.8-14.2), 18.6 months (95% CI: 15.9-21.8), and 26.6 months (95% CI: 23.5-30.7), respectively (p<0.00001) (Figure 1E). In the stratified analysis by age, these positive findings were only observed in the subgroup of patients diagnosed in the period from 2000 to 2015 (<65 years old: 24.6 months [95% CI: 22.1-28.8]; 65-75 years old: 19.1 months [95% CI: 15.6-23.7]; >75 years old: 15 months [95% CI: 9.4-18.5]; p<0.001) (Figure 1F). Regarding subsequent treatment lines (3rd and 4th), we did not observe statistically significant differences in TTNT neither by age nor by treatment periods. CONCLUSIONS: This study shows that the survival outcome have significantly improved over the last decades in all age groups, including the elderly, due to ASCT and novel drugs. The incidence of early mortality is low, being the most frequent MM progression and infectious complications. Finally, the time to second line treatment has increased, specifically during the period from 2000 to 2015, with no differences in subsequent lines. Disclosures Bladé: Janssen: Honoraria. Rosinol:Janssen, Celgene, Amgen, Takeda: Honoraria.

Mid-term outcomes of symptomatic isolated superior mesenteric artery dissection with endovascular management

Vascular ◽  
2020 ◽  
pp. 170853812095011
Author(s):  
Yingjiang Xu ◽  
Xuexin Li ◽  
Dan Shang ◽  
Jianyong Liu ◽  
Bi Jin ◽  
...  
Keyword(s):  
Artery Dissection ◽  
Endovascular Management ◽  
Technical Success ◽  
Positive Events ◽  
Technical Success Rate ◽  
Line Therapy ◽  
Group A ◽  
Group B ◽  
Superior Mesenteric Artery Dissection

Objectives The clinical outcomes, safety, and efficacy of endovascular management are explored for symptomatic isolated superior mesenteric artery dissection (ISMAD). Methods In this retrospective study, 51 consecutive patients with symptomatic ISMAD received endovascular management from three institutions between January 2011 and December 2019.These patients were categorized into group A (endovascular treatment was used as the first-line therapy) and group B(endovascular treatment was used as the second-line therapy). The general epidemiological data, clinical manifestations, first-episode symptoms, treatment process, imaging findings, follow-up outcomes were analyzed from the medical records. Results A total of 51 patients with endovascular management were collected in this study. Significant differences were observed between the two groups with respect to the course (150 h vs. 57 h; p < 0.001), intestinal ischemia (26.32% vs. 6,25%; p = 0.04) and dissection length (45.26 ± 13.78 mm vs. 63.37 ± 12.73 mm; p < 0.001). Technical success rate was 90.2% (46/51). There was significant difference in the MOD (42.27 ± 23.41 min vs. 76.63 ± 28.62 min p < 0.001), MPSRT (4.67 ± 2.65 h vs. 7.32 ± 2.49 h, p = 0.02), LOS (9.52 ± 3.72 days vs. 11.86 ± 4.13 days; p = 0.01) between the two groups. The bleeding complication rate was 7.84% (one patient in group A and three patients in group B). A total of 48 (94.12%, 48/51) patients were followed up for a median of 36.51 months (range, 4–87 months). Positive events of the SMA were achieved in 81.25% (39/48), and negative events of the SMA were achieved in 18.75% (8/48) based on the follow-up contrast-enhanced CT scan. Conclusions Endovascular management of symptomatic ISMAD has a high technical success rate and efficient at controlling symptoms. Furthermore, as more positive events occur, endovascular management should be encouraged early when pain persists after conservative management or there are signs of disease progression.

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.

Low Dose TBI Based Nonmyeloablative Conditionings for Allografting in Multiple Myeloma: Impact of Disease Status at Transplant.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2310-2310
Author(s):  
Luisa Giaccone ◽  
Marcello Rotta ◽  
Bernardino Allione ◽  
Fabrizio Carnevale-Schianca ◽  
Carlo Rosanelli ◽  
...  
Keyword(s):  
Complete Remission ◽  
Partial Response ◽  
Disease Progression ◽  
Stable Disease ◽  
Low Dose ◽  
Tumor Burden ◽  
P Value ◽  
Refractory Disease ◽  
Group A ◽  
Group B

Abstract The curative potential of allogeneic hematopoietic cell transplantation (HCT) with low dose total body irradiation (TBI) based conditionings relies exclusively upon a graft-versus-myeloma effect through donor lymphocytes. Thus, low tumor burden and well-controlled disease at transplant could play a pivotal role. Forty-four consecutive patients with myeloma were treated at 4 different Institutions. Thirty newly diagnosed patients (group A) received a planned autologous transplant with melphalan 200 mg/m2 followed by 200 cGy TBI and allogeneic G-CSF mobilized PBSC infusions from HLA identical siblings. Median time from diagnosis to HCT was 9 months (range, 5–46). At allografting, 7 (23%) patients were in complete remission (CR), 17 (57%) in partial response (PR) and 6 (20%) had refractory disease. The remaining 14 patients received fludarabine 90 mg/m2 and 200 cGy TBI followed by allogeneic PBSC from HLA identical siblings as salvage therapy (group B) after a median of at least 2 lines of previous chemotherapy (range, 2–5); all patients, except one, had received 2 autologous transplants. Patients in group B underwent allografting at a median of 37 months (range, 15–105) from diagnosis; 7 (50%) were in PR, 3 (21%) had refractory disease and 4 (28%) were in overt progression. Post-grafting immunosuppression consisted of cyclosporine and micophenolate mofetil in both groups. All patients readely engrafted with median donor T cell chimerism of 97% (range, 55–100%) at day 100. Overall, 64% (28/44) and 43% (19/44) patients developed acute graft-versus-host disease (GVHD) and chronic clinical extensive GVHD, respectively. There were no significant differences in engraftment kinetics and incidence of GVHD between the 2 groups. After a median follow-up of 16 months (range, 2–50) in group A and 19 months (range, 2–48) in group B, treatment related mortality was 23% among patients who received HCT earlier (group A) and 21% among those who were treated later (group B) in the disease course. Overall survival was 74% and 43% in group A and B, respectively. Disease responses are described in the table. n complete remission partial response stable disease progression Disease response Group A 30 17 6 7 0 Group B 14 0 0 3 11 p value – 0.0001 0.08 0.3 &lt;0.0001 Among patients in group A, 4 relapsed after obtaining CR. Three of them received donor lymphocyte infusion (DLI): 1 achieved CR, 1 PR and 1 had stable disease. Of the 14 patients in group B, 5 received DLI because of relapse/disease progression: 2 obtained PR, and 3 progressed. In conclusion, these findings indicate that graft-versus-myeloma effect appears more effective if HCT is performed earlier after diagnosis in patients with low tumor burden.

Use of Alkylating Agents Among Patients with Multiple Myeloma in a National Registry, 2006-2008.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4941-4941
Author(s):  
Carla M Van Bennekom ◽  
Theresa E Anderson ◽  
Noopur Raje ◽  
Kenneth C Anderson ◽  
David W Kaufman
Keyword(s):  
Multiple Myeloma ◽  
Median Duration ◽  
Research Funding ◽  
Alkylating Agents ◽  
Initial Therapy ◽  
Novel Agents ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Abstract 4941 Background While alkylating agents were among the earliest treatments for multiple myeloma, newer therapies have been available for several years. Here we describe patterns of use and effectiveness of alkylators in the modern landscape of myeloma treatment, based on a nationwide registry of recently diagnosed patients. Methods The “Patient Registries at Slone: Myeloma” is a national disease-based observational registry conducted by Boston University. All patients with myeloma diagnosed within 4 months of enrollment were eligible for inclusion. Subjects enrolled by mail or over the internet; information on treatment, clinical events, and quality of life was obtained by questionnaire and from medical record review at baseline and at six-month intervals. There were 342 patients with multiple myeloma residing in 43 states who were enrolled from June 2006-October 2008 and completed at least a baseline questionnaire. The median length of follow-up was 8 months after diagnosis (range 0.5-24). Results Alkylators were used as initial treatment in 26 patients (8%), as second-line treatment in 14 (4%), and as part of a transplant regimen in 76 (22%). Patients who received alkylators as initial or second-line therapy tended to be older (median age, 69 vs. 60 years, p<0.0005), and the combined prevalence of use was 17% among patients who did not have prescription drug insurance, compared with 11% among those who did (p=0.36). The prevalence of first-line use was 12% among patients diagnosed in 2006, 9% in 2007, and 4% in 2008 (p=0.09). Further results are confined to 34 of the 40 first or second-line alkylator recipients for whom medical records were available. The regimens used are shown in the table; the majority of patients received regimens that included melphalan. The median duration of initial therapy was 3 months (range 0.5-15); 6 patients (24%) had at least a partial response. Ten patients were still on treatment at the end of follow-up; in 15 (60%), alkylator therapy was changed to another regimen (11) or stopped without new therapy during the follow-up period (4), including 3 due to insufficient response and 5 due to toxicity. The new regimens were thalidomide-based in 2 patients, bortezomib-based in 3, bortezomib+lenalidomide in 1, dexamethasone without novel agents in 2, and 3 patients went directly to autologous stem-cell transplant. Second-line therapy with alkylators was initiated due to insufficient response from the previous regimen in 2 patients, because of side effects in 5, and for cost reasons in 2. The median duration was 2 months (range 0.5-12, with 4 patients still on treatment), and 4 (44%) had a partial or better response. The immediately preceding regimen was thalidomide-based in 5 patients, lenalidomide-based in 1, and bortezomib-based in 3; the median number of previous regimens was 2 per patient (range, 1-4). The median duration of previous therapy was 4 months (range 0.5-9). Conclusions The present population-based results indicate that in the modern era of myeloma treatment, the most prevalent use of alkylating agents is as conditioning for stem cell transplants; the drugs are also still used for initial treatment, mostly in combination with novel agents, although the prevalence was low overall and continued to decline during 2006-2008. Patients who received alkylators for initial or second-line therapy were older and the agents appeared to be somewhat more commonly used among those who did not have prescription drug insurance. The data suggest that there continues to be a useful role for alkylating agents as initial therapy, particularly for myeloma patients who are not transplant candidates, and occasionally as an early replacement for novel agents that prove ineffective or excessively toxic in individual patients. With a relatively short duration of follow-up, there was little information on the use of alkylators in the relapsed setting, where their high level of anti-myeloma activity might be expected to lead to more use. Disclosures Van Bennekom: Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding. Anderson:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding. Raje:Celgene: Research Funding; Novartis: Research Funding; AstraZeneca: Research Funding. Anderson:Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Kaufman:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding.

Continuous versus intermittent chemotherapy in metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3582-3582 ◽  
Author(s):  
C. G. Alexopoulos ◽  
A. A. Kotsori
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Stable Disease ◽  
Randomized Study ◽  
Intermittent Chemotherapy ◽  
Group A ◽  
Group B ◽  
Line Chemotherapy

3582 Background: The current policy concerning the duration of chemotherapy in metastatic colorectal cancer (MCC) varies considerably (Clin Oncol 1997;9:248) while no benefit of continuous versus intermittent 5-FU was found in a published randomized study (Lancet 2003;361:457). Serious cumulative toxicity is not usually a problem with long-term 5-FU/FA, but this is not the case with contemporary triple regimens (FOLFIRI, FOLFOX). We, therefore, performed a randomized study of continuous versus intermittent FOLFIRI as first line chemotherapy in MCC. Methods: Patients with MCC and ECOG 0–2 were given 6 biweekly courses of FOLFIRI (Irinotecan 180mg/m2 + De Gramont). Patients with response or stable disease were randomized to continue with another 6 FOLFIRI (group A) or discontinue until relapse when 6 FOLFIRI were readministered (group B). Time to progression (TTP) was calculated from study entrance until 1st progression for group A, and 2nd progression for group B, and overall survival (OS) from study entrance until death. Results: Fifty eight (M=38, F=20) patients entered into the study. Two (3.4%) withdrew before evaluation, 1 (1.7%) died of stroke, 1 (1.7%) was lost to FU and 15 (26%) progressed before or at the completion of 6 FOLFIRI. Thirty nine (67%) patients (M=25, F=14), median age 69 (38–79) responded (21=54%) or had stable disease (18=46%) and were randomized: 19 (49%) to group A and 20 (51%) to group B. Median TTP was 8 months 95% CI: 5.3–10.7) for group A and 9 (95% CI: 7.8–10) for group B (p=NS). 10/19 (52%) in group A received 2nd line chemotherapy vs 7/20 (35%) in group B (p=NS). With a median follow-up of 13 months, 21 patients are alive (12 in group A and 9 in group B). Median OS was 21 months (95% CI: 15 - 26.7) in group A vs 15 (95% CI: 12.6 - 17.3) in group B (p=NS), and 18 months (95% CI: 15.5 - 21) for all 39 patients. Conclusions: In MCC, when response or stability has been achieved after 6 courses ofFOLFIRI there seemstobe little more benefit from continuing chemotherapy than from retreating patients at relapse No significant financial relationships to disclose.

scholarly journals Disease progression and antiretroviral therapy in newly seropositive HIV subjects in a tertiary care hospital in North India

2013 ◽  
Vol 7 (02) ◽  
pp. 110-115 ◽  
Author(s):  
Sanjim Chadha ◽  
Preena Bhalla ◽  
Arun Kumar Jha ◽  
Hitender Gautam ◽  
Sanjeev Saini ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Disease Progression ◽  
Highly Active Antiretroviral Therapy ◽  
Tertiary Care ◽  
North India ◽  
Care Hospital ◽  
Cd4 Counts ◽  
Group A ◽  
Group B

Introduction: In developing countries the standard methods used to monitor HIV disease progression and therapy response are clinical assessment, CD4+ T lymphocyte count measurement, and plasma viral load (PVL) quantification. These tests require expensive equipment and skilled technicians, so monitoring HIV in resource-limited countries remains challenging as few laboratories can offer these tests free of cost. Methodology: Newly diagnosed HIV seropositive subjects (n = 130) were categorized into three study groups: CD4 counts <200 cells/µl (group A, 43 subjects); 200-500 cells/µl (group B, 44 subjects); and >500 cells/µl (group C, 43 subjects). At recruitment, PVL estimation was performed for group A subjects only, who were then initiated on highly active antiretroviral therapy (HAART) and were followed up after six months for evaluation of response to HAART by measuring the CD4 counts and PVL. Groups B and C were followed up after six months to monitor disease progression by measuring only CD4 counts. Results: Among group A subjects, a rise in the median CD4 counts after six months of HAART was observed. At baseline, PVL ranged from 2636 to >750,000 copies/ml with a median PVL at baseline of 165,000 copies/ml. At follow-up, 90% of the study subjects had undetectable levels of viraemia. Among group B and C subjects, a fall in the CD4 counts at follow-up was observed. Conclusions: CD4 count is a powerful tool to determine response to antiretroviral therapy (ART) and monitor disease progression in HIV/AIDS. PVL is important to assess response to ART, especially in immunovirologic discordant responses.

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