Sequential use of sorafenib and sunitinib in renal cancer: Retrospective analysis in 90 patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5038-5038 ◽  
Author(s):  
M. P. Sablin ◽  
L. Bouaita ◽  
C. Balleyguier ◽  
J. Gautier ◽  
C. Celier ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Risk Groups ◽  
Cross Resistance ◽  
Treatment Results ◽  
Duration Of Treatment ◽  
Best Response ◽  
Extended Access ◽  
Few Data ◽  
Metastatic Sites ◽  
Continuous Dosing

5038 Background: Sorafenib (So) and sunitinib (Su) have been recently approved for the treatment of advanced renal cell carcinoma (RCC). Following this approval, sequential use of both drugs is often proposed, although very few data are available to support it. Material and Methods: We reviewed all patients (pts) who received sequentially So-Su or Su-So in the last 3 years from 4 sites in France. All pts had been enrolled in clinical studies or in the extended access programs. In all patients demography, prognostic factors (MSKCC score), number of metastatic sites, best response (BR) and PFS with each treatment were recorded. Some patients are still too early for response and PFS assessment under the second treatment. Results: 68 pts first received So while 22 pts received Su first (continuous dosing in 12, intermittent in 10). Results under the first treatments were as follows: median PFS 26.1 wks, mean duration of treatment 33.2 wks; and median PFS was 22 wks, mean duration of treatment 26.9 wks for So and Su respectively. BR in terms of partial response (PR), stable disease (SD), progressive disease (PD) is given in the table . 2 pts stopped So because of toxicity and response is not available (NA), and 22 pts (NE) are too early in the course of the second treatment. Overall, PR rate was 17.6% for So and 22.7% for Su. PR or SD was observed as best response in the second treatment in both sequences. Only 6 pts had PD with both drugs: all of them had 3 or more metastatic sites and were in intermediate or poor MSKCC risk groups. Conversely, 4 pts had PR with both drugs, and were in good (n=2) or intermediate (n=2) risk groups. 11 pts only have died so far. Conclusions: these results suggest the lack of cross resistance between So and Su, and support the sequential use of So and Su in RCC. Updated data will be presented at ASCO. [Table: see text] No significant financial relationships to disclose.

Clinical outcomes according to ethnicity in patients with metastatic renal cell carcinoma (mRCC) treated with VEGF-targeted therapy (TT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16065-e16065
Author(s):  
Dominick Bosse ◽  
Wanling Xie ◽  
Connor Wells ◽  
Aly-Khan A. Lalani ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Risk Groups ◽  
Eligibility Criteria ◽  
Best Response ◽  
Metastatic Sites

e16065 Background: Discrepancies in clinical outcomes between different ethnic groups are well known in cancer patients. Differences in mRCC patients receiving VEGF-TT are less well characterized. We thought to report on baseline characteristics and treatment outcomes in African-Americans (AA) and Hispanic patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Methods: Caucasians, AA and Hispanics with mRCC treated with 1stline VEGF-TT were identified from the IMDC. We created 2 matched cohorts: 1) AA vs. Caucasians and 2) Hispanics vs. Caucasians, both matched for age (<50; 50-59; 60-69; <70-year-old), gender, years of treatment (2003-07; 2008-12; 2013-16) and geography (Canada, USA, Europe). Weighted Cox and logistic regressions were used to compare OS, time-to-treatment failure (TTF) and best response, adjusted for nephrectomy status, IMDC risk groups, number of metastatic sites (1 v. >1) and histology (clear-cell vs. else). Results: 73 AA and 71 Hispanics met eligibility criteria and were matched with 1236 and 901 eligible Caucasians, respectively. AA had more non-clear cell histology (26% v. 11%), time from diagnosis to therapy<1 year (67% v. 55%) and anemia (75% v. 54%) vs. Caucasians. Differences were not significant for Hispanics. Clinical outcomes are presented in Table. Conclusions: Adjusted for clinical prognostic factors, Hispanics with mRCC have statistically shorter TTF and survival than Caucasians. AA had a trend toward shorter TTF (not significant) but similar survival than Caucasians. Underlying genetic/biological differences, along with potential cultural variations, may impact survival in Hispanic mRCC patients. [Table: see text]

Does neutrophil to lymphocyte ratio correlate with toxicities and outcome of patients with genitourinary cancers treated with checkpoint inhibitors?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16032-e16032
Author(s):  
Marco Maruzzo ◽  
Francesco Pierantoni ◽  
Umberto Basso ◽  
Filippo Maria Deppieri ◽  
Michele Dionese ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Checkpoint Inhibitors ◽  
Response Assessment ◽  
Steroid Treatment ◽  
Neutrophil To Lymphocyte Ratio ◽  
High Dose ◽  
Lymphocyte Ratio ◽  
Single Center Experience ◽  
Best Response ◽  
Few Data

e16032 Background: Few data are available concerning the role of neutrophil and lymphocyte counts in predicting toxicities and outcome in patients (pts) with genitourinary cancer treated with recent immunotherapy. Methods: We retrospectively reviewed the clinical charts of all pts with metastatic renal cell (RCC) or urothelial cancer (UC) treated at our Institute with immunotherapy(Nivolumab with or without Ipilimumab, Atezolizumab, Durvalumab, Pembrolizumab), having at least one response assessment after starting treatment. Results: We identified 117 pts treated from May 2015 onwards, median age: 68 years (range 39-84), 72% males, 53% with UC. Incidence of G3/4 toxicities was 17%, while 23.9% of pts needed an high dose steroid treatment because of immune-related toxicities (IrT). Median PFS and OS were 7.0 and 24.1 months, respectively for RCC, and 2.8 and 7.1 months, respectively for UC. 56 pts had progressive disease at best response. Baseline value of neutrophils or lymphocytes does not correlate with IrT (t test, p = 0.399, p = 0.728, respectively). In the IrT events, no significant increase of lymphocytes was detected (p = 0.160). The incidence of a IrT which needed steroid treatment positively impact in PFS (p = 0.03) but not in OS (p = 0.74). The use of steroid therapy was not associated with a different outcome in terms of OS (p = 0.49 for UC and p = 0.18 for RCC) and associated with a better PFS in RCC (p = 0.018). Steroid use was associated with the probability of non-progressive disease at first assessment (Chi-squared test, p = 0.015). In our cohort, baseline neutrophil to lymphocyte ratio (NLR) ≥ 3 correlate with a shorter PFS and OS in UC (p = 0.026 and p = 0.003 respectively), while it does not in RCC (p = 0.104 and p = 0.678 respectively). In our cohort, baseline neutrophil to lymphocyte ratio (NLR) ≥ 3 correlate with a shorter PFS and OS in UC (p = 0.026 and p = 0.003 respectively), while it does not in RCC (p = 0.104 and p = 0.678 respectively). In UC, the positivization of NLR after 2 cycles predicts a shorter PFS for UC (p = 0.008) and a trend for OS. Conclusions: In our retrospective single-center experience, NLR confirms its role in UC even in a cohort treated with immunotherapy and its variation predicts shorter outcome, while neutrophils or lymphocytes do not relate with IrT. The use of steroid for IrT is safe since it does not impact on survival and is associated with a higher probability of non-progressive disease at first assessment.

scholarly journals Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3776
Author(s):  
Edouard Auclin ◽  
Perrine Vuagnat ◽  
Cristina Smolenschi ◽  
Julien Taieb ◽  
Jorge Adeva ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Prognostic Index ◽  
Predictive Marker ◽  
Risk Groups ◽  
Two Factors ◽  
One Year ◽  
Metastatic Sites ◽  
Tumor Types

Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p <0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46–8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.

Phase II study of SM-88 in Ewing's and other sarcomas.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23505-e23505
Author(s):  
Victoria S. Chua ◽  
Sant P. Chawla ◽  
Kitty Zheng ◽  
Ted Kim ◽  
Giuseppe Del Priore ◽  
...  
Keyword(s):  
High Risk ◽  
Prospective Trial ◽  
Median Number ◽  
Cross Resistance ◽  
Duration Of Treatment ◽  
Open Label ◽  
Durable Response ◽  
Phase 2 Trial ◽  
Acid Analogue ◽  
Prior Systemic Therapy

e23505 Background: Sarcomas are rare heterogeneous malignancies. Once recurrent, cure is uncommon. SM-88 (racemetyrosine) is an amino acid analogue with no known cross resistance to typical sarcoma regimens. Based on previous anecdotal experience in Ewing’s (EWS) we initiated a Phase 2 trial (HopES) in EWS and other sarcomas (Ss) after >1 prior systemic therapy. We now report preliminary data after having met prespecified continuation criteria. Methods: Open label prospective trial in 2 separate cohorts (EWS and Ss) of oral SM-88 used with MPS conditioning agents (SM-88 920 mg, methoxsalen 10 mg, phenytoin 50 mg, sirolimus 0.5 mg) all daily until progression. Results: As of Feb 5 2021, 10 pts with incurable sarcomas were enrolled; 4 had high risk but stable EWS. Average age 43.9 yrs (13–77); 70% white; 20% female. Median number of prior regimens 4 (1–9); 70% received prior RT; 50% prior surgery. Median time from initial diagnosis 39.5 months with 50% T2 (40% unknown), 30% M1 (30% unknown). Prespecified futility stopping was exceeded (i.e., >1 of first 5 subjects/cohort) upon achieving clinical benefit in each. Stable disease was achieved in 75.0% (6/8 with available data). Time on treatment (TTx) exceeded last known TTx in 80% (95% CI 44.4–97.5). Median SM-88 TTx was 4.9 vs 2.9 mo for prior TTx (logrank HR 0.53; p=0.12). One EWS subject had unresectable disease that became resectable, was completely resected, and remained disease-free for ≥ 6 months. Prior to SM-88, longest TTx was 12 mo (on IT*) and shortest TTx 1 mo (on IEV*) vs SM-88 TTx of 11.9 mo. An angiosarcoma subject had a 21% reduction in the sum of all target lesions and exceeded all prior TTx (including 8 mo on Ap/N* with 12+ mo duration of treatment of SM-88). There were no serious drug-related AEs. ECOG performance remained stable for all. Conclusions: SM-88 has exceeded pre-specified futility in both cohorts (EWS maintenance and Ss salvage). HopES continues to enroll toward the planned total of 12 subjects to more precisely define its benefit in this ultra-orphan, extremely recalcitrant disease. This trial now confirms the previously reported clinical utility of oral SM-88 in EWS and other high-risk sarcomas. Based on durable response (>6mo), SD and prolonged TTx, SM-88 warrants additional investigation in this setting. Clinical trial information: NCT03778996. [Table: see text]

Overall survival benefit from tebentafusp in patients with best response of progressive disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9509-9509
Author(s):  
Anthony M. Joshua ◽  
Jean-Francois Baurain ◽  
Sophie Piperno-Neumann ◽  
Paul Nathan ◽  
Jessica Cecile Hassel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Safety Profile ◽  
Progressive Disease ◽  
Analysis Data ◽  
Cell Receptor ◽  
Kaplan Meier ◽  
Immortal Time Bias ◽  
Best Response ◽  
Overall Survival Benefit

9509 Background: Tebentafusp (tebe) is the first T cell receptor (TCR) therapeutic to demonstrate an overall survival (OS) benefit in a randomized Phase 3 (Ph3) study [ NCT03070392 ]. In Ph2, 42% of pts with best overall response (BOR) of progressive disease (PD) survived > 1 year (yr), suggesting RECIST-based radiographic assessments underestimate OS benefit of tebe. Here we analyzed OS in the Ph3 study in a cohort of pts with BOR of PD by comparing tebe to the control arm of investigator’s choice (IC). Methods: 378 pts were randomized in a 2:1 ratio to tebe vs. IC. BOR was assessed by investigators using RECIST v1.1. Treatment beyond first disease progression (TBP) was permitted for both arms. On the IC arm, only patients receiving pembrolizumab (pembro) continued with TBP and were included in the TBP-related analyses. No crossover to tebe was permitted; investigators were free to choose subsequent therapy. This analysis was conducted on the first interim analysis (data extracted Nov-2020). Kaplan-Meier estimates of OS were based on Day 100 landmark to eliminate immortal time bias and to capture majority of the PDs. Results: By Day 100, PD as BOR occurred in 52% (130/252) of tebe pts (PD-tebe) vs. 60% (76/126) of IC pts (PD-IC). Key baseline characteristics including lactate dehydrogenase, alkaline phosphatase, ECOG performance, age, and sex were similar between PD-tebe vs PD-IC. The proportion of pts with PD due to progression of target lesions (TL), non-TL, or new lesions were also similar between the two groups. More pts received TBP among PD-tebe 53% (69/130) vs PD-pembro 16% (10/61). Median duration of TBP was longer for PD-tebe (7 weeks) vs PD-Pembro (3 weeks). The safety profile of PD-tebe pts during TBP was similar to all tebe-treated pts. OS was superior for PD-tebe vs PD-IC, HR = 0.41 (95%CI 0.25-0.66), even when considering key baseline covariates. While some pts had regression of TL despite diagnosis of PD ( < 10% of pts), the OS benefit remained even when limited to pts with best change of tumor growth of TL, HR 0.46 (0.29, 0.73). 58% (75/130) PD-tebe and 52% (40/76) PD-IC pts received subsequent therapies. In a landmark OS analysis of these pts beginning on 1st day of subsequent therapy, prior tebe was associated with better OS vs. prior IC, HR 0.59 (95%CI 0.36-0.96). Conclusions: Tebe is the first TCR therapeutic to demonstrate an OS benefit in a solid tumor. Surprisingly, a strong OS benefit from tebe is observed even in pts with BOR of PD, suggesting that RECIST-based radiographic assessments do not capture the complete benefit from tebe. The safety profile of tebe during TBP was consistent with that for long-term tebe treatment. Clinical trial information: NCT03070392.

scholarly journals Functional assessment of foot and ankle tendinopathies treated with tendoscopy

2021 ◽  
Vol 15 (2) ◽  
pp. 128-132
Author(s):  
Rodrigo Guimarães Huyer ◽  
Mário Sérgio Paulillo Cillo ◽  
Carlos Daniel Cândido Castro Filho ◽  
Hallan Douglas Bertelli ◽  
Renato Morelli Berg
Keyword(s):  
Functional Assessment ◽  
Descriptive Analysis ◽  
Case Series ◽  
P Value ◽  
Peroneal Tendon ◽  
Foot And Ankle ◽  
Treatment Results ◽  
Duration Of Treatment ◽  
Aofas Score ◽  
Level Of Evidence

Objective: To assess postoperative clinical functional outcomes, based on the American Orthopaedic Foot & Ankle Society (AOFAS) score, of tendoscopies performed in the treatment of foot and ankle pathologies. Methods: Our comparative assessment used AOFAS scores obtained preoperatively and at early and late postoperative stages - 1 month and 6 to 12 months after surgery - of 14 patients with foot and ankle tendinopathies. These included peroneal tendon dislocation, peroneal tendonitis, and tearing of the peroneus longus or brevis, all treated with tendoscopy for peroneal reconstruction and tenorrhaphy. The AOFAS score was obtained by functional assessment during outpatient physical examination. We presented a descriptive analysis of cases, comparing scores over time through the Friedman test followed by Dunn’s test. The relationship between score variations and sex was assessed using the Mann-Whitney test; their comparison with age used Spearman’s linear correlation coefficient. Significance levels were 5%.Results: The AOFAS score showed important improvements such as preoperative scores of 56 and 67 followed by postoperative scores of 100 both in the early and late stages, supporting the efficacy and persistence of this treatment strategy. The p-value obtained after statistical analysis was <0.0001. Conclusion: We concluded that the treatment of foot and ankle comorbidities with tendoscopy, in addition to being less invasive, shows consistency and efficacy as demonstrated by the AOFAS score and functional assessment via postoperative physical examinations. AOFAS scores were increased and maintained at high levels in the postoperative period, demonstrating the efficacy of this procedure and the duration of treatment results. Level of Evidence IV; Case Series; Therapeutic Studies - Investigation of Treatment Results.

Durability of response to immune checkpoint inhibitors (ICI) in metastatic Merkel cell carcinoma (mMCC) after treatment cessation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9543-9543
Author(s):  
Alison Margaret Weppler ◽  
Laetitia Da Meda ◽  
Ines Silva ◽  
Wen Xu ◽  
Giovanni Grignani ◽  
...  
Keyword(s):  
Median Time ◽  
Checkpoint Inhibitors ◽  
Initial Response ◽  
Leptomeningeal Disease ◽  
Treatment Cessation ◽  
Cns Involvement ◽  
Duration Of Treatment ◽  
Disease Characteristics ◽  
Best Response

9543 Background: mMCC is a rare, aggressive neuroendocrine cancer which often occurs in older patients (pts) with multiple comorbidities. While initial response rates to ICI are high, optimal treatment duration, durability of response after treatment cessation and response to retreatment with ICI is unknown. Methods: mMCC pts from 12 international centres who received at least one dose of ICI and subsequently stopped treatment without progression for a minimum of 12 weeks were studied. Demographics, disease characteristics and treatment course were examined. Results: 40 pts with mMCC were included. Pt characteristics are summarised in Table. Median time on treatment was 13.5 months (range 1 to 35). Median time to best response was 4.5 months (range 1 to 17) and median time receiving treatment after best response was 8 months (range 0 to 29). 25 pts (63%) stopped primarily due to being in a complete or partial response (CR or PR), 9 (23%) due to toxicity and 6 (15%) due to other reasons, primarily pt choice or comorbidities. At time of discontinuation, 30 pts (75%) were in a CR, 8 (20%) in a PR and 2 pts (5%) had stable disease (SD). After a median follow up of 12 months from discontinuation, 14 pts (35%) have progressed (PD); 5 (36%) at a previous site, 5 (36%) at a new site and 4 (29%) at both. PD occurred after a median of 5.5 months (range 4 to 29) off treatment. 4 pts (29%) had a CNS recurrence, none of whom previously had CNS involvement. Pts in CR at time of discontinuation were less likely to progress (CR: 26% PD vs non-CR: 67% PD, p=0.044), but still had a considerable rate of PD (CR: 26%, PR: 57%, SD: 100%). Those who progressed had numerically less cycles of ICI prior to treatment cessation (17 vs 32, p>0.05). Baseline disease factors, time to best response and duration of treatment after best response were not associated with PD. ICI was restarted in 8 of 14 pts (57%) with PD, with response rate to retreatment of 75% (4 CR, 2 PR, 1 SD, 1 PD – pt with leptomeningeal disease). Median time to best response at retreatment was 3 months (range 2 to 7), with all responses ongoing after a median of 10 months back on treatment. 3 pts had an isolated site of PD successfully treated with radiation therapy and remain in remission off ICI. Conclusions: ICI responses in mMCC do not appear as durable off treatment as in other cancers, including in patients who achieve a CR. Ongoing treatment should be considered, though initial data on response to retreatment is promising.[Table: see text]

Association of response to first-line chemotherapy with the efficacy of atezolizumab in patients with metastatic urothelial carcinoma.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 409-409
Author(s):  
Deniz Tural ◽  
Omer Fatih Olmez ◽  
Ahmet Taner Sümbül ◽  
Mehmet Artac ◽  
Nail Ozhan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Clinical Benefit ◽  
Progressive Disease ◽  
Univariate Analysis ◽  
First Line ◽  
Exact Test ◽  
Best Response ◽  
Metastatic Urothelial Carcinoma ◽  
Line Chemotherapy

409 Background: In the current study, we evaluated whether the response first-line chemotherapy could impact atezolizumab benefit in terms of response rate and overall survival in patients with metastatic urothelial carcinoma. Methods: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. The association between response to first-line chemotherapy and ATZ was assessed using Fisher’s exact test. Overall survival (OS) was estimated by using the Kaplan-Meier method. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p˂0.1) and then included the final model if p˂0.05. Results: Best response to first-line chemotherapy was complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) in 5(4.8%), 38(36.2%), 16(15.2%), 46(43.8%) patients, respectively. Best response to atezolizumab was CR, PR, SD, PD in 9(8.6%), 22(21%), 23(21,9%), 51(48,5%). Forty (74.1%) of patients who benefited from first-line chemotherapy also benefited from atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with atezolizumab (Fisher’s exact test, p=0.001). Patients with clinical benefit from first-line chemotherapy had a higher OS. The median OS of atezolizumab were 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (log-rank p=0.001). In univariate analysis, Patients with clinical benefit from first-line chemotherapy, liver metastases, baseline creatinine clearance less (GFR)than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all significantly associated with OS. Three of the adverse prognostic factors according to the Bellmunt criteria were independent factor of short survival: liver metastases (Hazard Ratio [HR]= 0.6; 95% CI 0.174-0.60; p=0.04), ECOG PS≥1 (HR= 0.36; 95% CI 0.2-0.66; p=0.001), and Hemoglobin level below 10 mg/dl (HR= 0.36; 95% CI 0.2-0.66; p <0.001). In addition, Patients with clinical benefit from first-line chemotherapy (HR= 0.39; 95% CI 0.24-0.65; p <0.001) maintained a significant association with OS in multivariate analysis. Conclusions: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factor on OS in patients' use of atezolizumab as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

scholarly journals Very low dose alpha-2b interferon for the treatment of hairy cell leukemia [see comments]

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1440-1443 ◽  
Author(s):  
JA Thompson ◽  
P Kidd ◽  
E Rubin ◽  
A Fefer
Keyword(s):  
Hairy Cell Leukemia ◽  
Low Dose ◽  
Progressive Disease ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Duration Of Treatment ◽  
Previous Response ◽  
Interferon Alpha 2B ◽  
Antileukemic Effect ◽  
Ifn Therapy

Abstract Alpha-2b interferon (alpha-2b IFN), administered at 2 x 10(6) U/m2 three times per week is highly effective in the treatment of progressive hairy cell leukemia (HCL) and in the retreatment of patients who have relapsed after previous IFN therapy. To determine if a lower interferon dose would induce a comparable antileukemic effect with less toxicity, a-2b IFN was administered at 2 x 10(5) U/m2 subcutaneously three times per week to 17 patients with progressive HCL. Thirteen patients had HCL in relapse after a previous response to alpha-2b IFN; four patients were previously untreated. The median duration of treatment was 9 months. Toxicity consisted only of transient, mild flu-like symptoms in two patients. Of the 13 previously IFN-treated patients, four had a minimal response, one had no response, and eight had progressive disease. Of four previously untreated patients, one had a partial response, two had a minimal response, and one had no response. In seven of eight patients whose disease progressed on low-dose IFN, the dose was escalated to 2 x 10(6) U/m2 three times per week, and all seven patients demonstrated hematologic response within 3 months to the dose escalation. We conclude that alpha- 2b IFN at 2 x 10(5) U/m2 three times per week is relatively ineffective for the treatment of relapse after previous IFN therapy.

Fludarabine Plus Cyclophosphamide and Rituximab In Waldenström's Macroglobulinemia: Results In 55 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1757-1757
Author(s):  
Véronique Leblond ◽  
Laetitia Compain ◽  
Vincent Levy ◽  
Jérôme Tamburini ◽  
Alain Delmer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Progressive Disease ◽  
Response Rate ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Best Response ◽  
Previously Treated ◽  
Delayed Responses

Abstract Abstract 1757 Treatment of Waldenström's Macroglobulinemia relies on alkylator agents, nucleoside analogs and/or monoclonal antibody based therapies. We showed previously that combination of fludarabine and cyclophosphamide yields a 78% response rate (RR). We performed a retrospective study in 55 WM patients (pts) treated with RFC regimen in 10 French centers. The median age was 65 years (range: 34–79), the median IgM level measured by electrophoresis was 27.3 g/L (range: 6.5–64), the median haemoglobin level was 9.7g/dl (range: 3.7–14), the median platelet count was 174 × 109/L (range: 22–500), the median beta 2 microglobulin level was 3.4 mg/l (range: 1.7–9). In all, 40/55 pts had previously been treated with a median of 2 lines of therapy (range: 1–4), including 24 patients with relapsed disease and 16 patients with refractory disease. RFC regimen was given every 4 weeks and consisted in: Rituximab 375 mg/m2 IV Day 1, Fludarabine 40 mg/m2 per os Day 1 to Day 3, Cyclophosphamide 250 mg/m2 per os Day 1 to Day 3. 55 pts received the first cycle of RFC, and 52 received two or more cycles (median of 4 cycles, range 2–6). Main toxicity was hematological. No toxic death was observed.Response was assessed 3 months after the last RFC cycle according to response criteria agreed by the 3rd International Workshop on WM (Kimby, 2006), but delayed responses with improvement of the response occurring more than 3 months after treatment discontinuation were observed in 15 patients. The best response was evaluated in 51 pts (3 early discontinuation treatments, one progressive disease), including 26 partial responses (PR), 5 minor responses (MR), and 2 stable diseases (SD). Of note 18 very good PR/ near RC (VGPR) were observed (> 90% decrease in M-protein) . The overall response rate was 89%. Long lasting cytopenia was observed in 10 patients. In the untreated group one pt in failure had a Burkitt-like lymphoma, the other 14 pts are alive in response. In the previously treated group, 6 pts relapsed, one developed a large B-cell lymphoma. Three ASCT and 4 allogeneic SCT were performed in six patients. With a median follow-up time of 28 months, median time to treatment failure (TTF) was not reached, even in previously treated patients. There was not significant difference in the TTF duration in patients in VGPR compared with those in PR + MR.The median progression free survival time was not reached. Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was observed in two heavily treated patients and 3 pts had a secondary solid cancer. In all, 48 pts are alive, 7 patients died (4 from progressive disease, 2 from secondary cancer, and 1 from Burkitt-like transformation). Conclusion: RFC combination even in heavily treated patients with poor prognostic factors gives a very high response rate (89%) with 33% of patients achieving at least a very good partial response with acceptable toxicity. The toxicity on the hematopoietic stem cell reservoir is a major concern. This combination could be offered to relapsed/refractory patients. In first line, the choice of this combination must be discuss, increased incidence of MDS/ AML after purine analogs, and impairment of stem cell mobilization having previously been reported by us and others. Because frequent delayed responses, a long follow-up with periodic electrophoresis is needed to assess the best response after RFC. Disclosures: Leblond: ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GENZYME: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; JANSSEN: Membership on an entity's Board of Directors or advisory committees. Tournilhac:MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees; GENZYME: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees. Choquet:ROCHE : Consultancy.

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