scholarly journals Maintenance Therapy in First-Line Gastric and Gastroesophageal Junction Adenocarcinoma: A Retrospective Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Daniel Walden ◽  
Mohamad Bassam Sonbol ◽  
Skye Buckner Petty ◽  
Harry H. Yoon ◽  
Mitesh Borad ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Retrospective Analysis ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Gastroesophageal Junction ◽  
Continuous Treatment ◽  
Comparable Efficacy ◽  
Continuous Group ◽  
Induction Treatment ◽  
Platinum Based Chemotherapy

BackgroundFluoropyrimidine with platinum-based chemotherapy has become the standard of care for advanced gastric and gastroesophageal (GEJ) cancer. Trials in colon cancer show that induction chemotherapy followed by maintenance chemotherapy is an efficacious strategy to maximize clinical response while minimizing toxicity. The current retrospective study aims to evaluate the efficacy and tolerability of maintenance versus continuous treatment in advanced GEJ malignancy.MethodsA retrospective analysis of patients with metastatic gastric/GEJ adenocarcinoma treated with fluoropyrimidine and platinum chemotherapy between 2007-2017 was performed. Patients who achieved at least stable disease after initial induction treatment were included. After 16 weeks of induction chemotherapy, patients were categorized into the continuous group if induction chemotherapy was continued and the maintenance group if chemotherapy was switched to maintenance fluoropyrimidine monotherapy or observed off treatment. Endpoints were progression-free survival (PFS), overall survival (OS), and toxicities.ResultsIn total, 90 patients met the criteria, 48 received continuous therapy, and 42 received maintenance. Baseline characteristics were comparable. No difference in PFS (9.9 vs 8.4 months p = .28) or in OS (16.1 vs 21.3 months p = .75) was observed, including after controlling for the best response on induction therapy and other variables. In patients on continuous induction therapy, there was a higher prevalence of grade three neuropathy (42.6% vs 9.8% p = .001) and neutropenic fever (13% vs 0% p =.03).ConclusionsMaintenance therapy following induction fluoropyrimidine and platinum-based therapy is associated with an improved toxicity profile and appears to have comparable efficacy to continuous treatment in metastatic gastric/GEJ cancer.

Prognostic Impact of the MRD Status After Induction Treatment with Rituximab Plus Fludarabine, Cyclophosphamide and Mitoxantrone (R-FCM) in Patients with Chronic Lymphocytic Leukemia Receiving Rituximab Maintenance Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3930-3930
Author(s):  
Pau Abrisqueta ◽  
Neus Villamor ◽  
María José Terol ◽  
Eva González-Barca ◽  
Marcos González ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Maintenance Therapy ◽  
Clinical Response ◽  
Induction Therapy ◽  
Maintenance Treatment ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Prognostic Impact ◽  
Rituximab Maintenance ◽  
The Impact

Abstract Abstract 3930 Chemoimmunotherapy combination regimens achieve high rates of negative minimal residual disease responses in CLL, which has been correlated with prolonged PFS and OS. In the present study, we addressed the prognostic value of MRD levels obtained after rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) induction treatment in the response duration of patients with CLL included in the GELLC-1 trial and receiving maintenance rituximab treatment (Bosch et al. J Clin Oncol 27:4578–4584, 2009). Patients achieving CR or PR after R-FCM induction received rituximab maintenance consisting of rituximab 375 mg/m2 every three months for two years (up to 8 cycles). MRD was evaluated by four-color flow cytometry assays giving a sensitivity < 10−4 in paired peripheral blood (PB) and bone marrow (BM) samples three months after R-FCM induction therapy, every 6 months during rituximab maintenance, and at the final restaging 3 months after conclusion of treatment. Sixty-seven patients (median age 60 years, 70% male) received a median of 8 cycles of rituximab maintenance (range, 1 to 8), 76% of them completing the entire planned treatment. After R-FCM induction, MRD was considered negative in 45/59 patients (76%) in PB and in 35/63 patients (55%) in BM. Of note, these patients with negative MRD in PB had longer PFS in comparison to those with detectable MRD (at 4 years, 88%, [95%IC 98%-78%] vs 27%, [95%IC 51%-3%] respectively; p<0.01) (Figure 1). MRD negativity in BM showed a trend for a prolonged PFS (p=0.056). When MRD levels in BM after R-FCM induction where categorized, we observed that PFS was similar between the MRD negative (<10−4; n=35) and intermediate (>10−4 to <10−2; n=20) subgroups, whereas it was significantly shorter in patients showing high (>10−2, n=8) MRD levels (PFS at 4 years, 84%, 74%, and 25%, respectively, p<0.01). MRD levels after RFCM induction were compared between PB and BM paired samples. Whereas 12/57 patients (21%) that were MRD negative in PB resulted positive in BM, all patients with negative MRD in BM also had negative MRD in PB. Patients with discrepancies (negative in PB but positive in BM) in their MRD status presented a similar PFS than those with negative MRD in BM (4 year PFS, 85% vs. 90%, P=NS). The impact of MRD levels in PB achieved after R-FCM induction on PFS was also analyzed. MRD status proved to be a superior predictor for PFS than clinical response (Figure 2). In addition, when different prognostic variables (lymphocyte doubling time [LDT, cutoff 12 months], ZAP-70, serum ß2microglobulin and LDH, cytogenetic abnormalities, and MRD levels) were analyzed as predictors for PFS, only MRD status in PB along with LDT remained significantly predictive. After rituximab maintenance, 40.6% of patients achieved a MRD-negative CR, 40.6% a MRD+ CR, 5% a PR, and 14% failed to treatment. Median time to conversion from negative to positive MRD was 45.4 months, significantly longer than that observed in patients treated with FCM only (45.4 vs. 16.4 months; p=0.011) (Bosch et al. Clin Can Res 14:155–161,2008). Moreover, 3 patients that achieved MRD negative in PB but remained MRD positive in BM after the initial R-FCM treatment, became MRD-negative in BM upon rituximab maintenance. Patients that remained MRD negative in PB at the end of rituximab maintenance treatment had an excellent outcome with a PFS of 93% at 4 years in comparison to 68% in patients with MRD positive status (p=0.016). In conclusion, in patients receiving rituximab maintenance MRD levels obtained after R-FCM induction correlated with PFS duration, this correlation being independent of the clinical response attained. The sensitivity of the detection of MRD in these patients was higher in BM than in PB. Finally, maintenance treatment with rituximab seems to prolong the PFS of patients with MRD positive status, minimizing the negative impact of low levels of MRD after induction therapy. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures: Off Label Use: Rituximab is currently not approved as maintenance therapy for patients with chronic lymphocytic leukemia. Bosch:Hoffman La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals The Effect of Different Rituximab-Containing Chemotherapy Strategies on Hepatitis C Viremia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4448-4448
Author(s):  
Parag Mahale ◽  
Francesco Turturro ◽  
Jorge Romaguera ◽  
Nathan Fowler ◽  
Harrys A. Torres
Keyword(s):  
Hepatitis C ◽  
Maintenance Therapy ◽  
B Cell ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Research Funding ◽  
Hcv Rna ◽  
Continuous Variables ◽  
Maintenance Chemotherapy ◽  
Before And After

Abstract Background: Rituximab (RXB) -containing chemotherapy forms the backbone of treatment for CD20 positive non-Hodgkin's lymphomas (NHL). RXB is combined with other agents as induction chemotherapy or as a single-agent maintenance therapy for indolent NHLs. RXB has been associated with reactivation of chronic hepatitis C virus (HCV) infection – a condition that leads to discontinuation of chemotherapy in 45% of patients who experience it. However, there is no data on the occurrence HCV reactivation according to the different types of RXB treatment strategies administered. We evaluated the effect of various RXB-containing regimens on HCV viremia. Methods: Medical records of all patients with NHL seen at MD Anderson between 01/2008-05/2014 were screened. Records of those who were treated with RXB-containing regimens and had HCV RNA levels available before and after chemotherapy were analyzed. HCV reactivation was defined as an increase of HCV RNA of ≥ log10IU/mL over pre-chemotherapy levels. Acute exacerbation of HCV infection (AcEx) was defined as an increase of alanine aminotransferase (ALT) levels of ≥ 3 times upper normal limit in the absence of liver infiltration of cancer, hepatotoxic drugs, recent transfusion, and coinfections. The groups compared were those who received RXB + chemotherapy (induction), with those who received RXB + chemotherapy followed by RXB maintenance therapy. Categorical variables were compared using χ2 or Fisher's exact test and continuous variables were compared using Wilcoxon rank sum test. Within each group, continuous variables before and after chemotherapy were compared using Wilcoxon signed-rank test. All P values < 0.05 were considered statistically significant. Results: We analyzed 28 HCV-infected patients (14 prospectively; 14 retrospectively) who received RXB-containing chemotherapy. Most patients were males (64%), whites (57%), and had a median age of 54.7 years (interquartile range, 47.8 – 61.4 years). Types of NHL included diffuse large B cell (54%), follicular (21%), marginal zone B cell (11%), mantle cell (4%), lymphoplasmacytic (4%), small lymphocytic (4%), and undetermined low grade B cell (4%) lymphomas; mostly Ann Arbor stage IV (82%). HCV genotype 1 was the most predominant strain (72%). Very few patients (12%) had cirrhosis when RXB chemotherapy was initiated. HCV treatment was administered before RXB chemotherapy in 9 (32%) patients but no one had resolved viremia (sustained virological response) at the time of cancer treatment. Overall, 43 courses of RXB-containing chemotherapy were administered, mostly as induction therapy (n = 39; 91%). Most common RXB-containing regimens administered were R-CHOP (n = 13; 30%), R-ICE (n = 6; 14%), and RXB with bendamustine (n = 5; 12%). In the entire cohort, when compared to pre-chemotherapy baseline levels, there were significant elevations in HCV RNA (median, log10IU/mL; 6.6 vs. 6.9; P = 0.005) and ALT (median, IU/L; 50 vs. 115; P < 0.0001) only after administration of RXB as induction chemotherapy, with no significant changes being found after RXB maintenance chemotherapy [HCV RNA (6.8 vs. 6.7; P = 1.0); ALT (37 vs. 59; P = 0.07)] (See Figure). When compared to maintenance therapy, those who received induction therapy attained peak HCV RNA (median, days; 590 vs. 140; P = 0.006) and peak ALT (median, days; 172 vs. 43; P = 0.02) earlier after RXB administration. HCV reactivation occurred only when induction chemotherapy was administered (n = 7). Doses of RXB-containing chemotherapeutic agents had to be modified (reduced or postponed) in 4 out of the 7 (57%) episodes of HCV reactivation. Median relapse-free survival for those who had dose modifications was lower than those without (14.6 months vs. 20.1 months; P = 0.13). Conclusion: HCV reactivation occurs after administration of RXB as a part of induction, but not maintenance chemotherapy for NHL. This virologic condition is associated with dose modification of RXB-containing chemotherapeutic regimens in over one-half of cases. Figure: Figure 1 Figure 1. Disclosures Torres: Gilead Sciences: Consultancy; Merck & Co., Inc. : Consultancy, Research Funding; Vertex Pharmaceuticals: Consultancy, Research Funding; Genentech,: Consultancy.

scholarly journals Capecitabine in Combination with Endocrine Therapy as Maintenance Therapy after Bevacizumab plus Paclitaxel Induction Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: KBCSG-TR1214

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4399
Author(s):  
Norikazu Masuda ◽  
Tetsuhiro Yoshinami ◽  
Masahiko Ikeda ◽  
Makiko Mizutani ◽  
Miki Yamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Maintenance Therapy ◽  
Endocrine Therapy ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Hazard Ratio ◽  
Time To Failure

Optimal treatment strategies for hormone receptor (HR)-positive, HER2-negative advanced and/or metastatic breast cancer (AMBC) remain uncertain. We investigated the clinical usefulness of adding capecitabine to maintenance endocrine therapy after induction chemotherapy and the efficacy of reinduction chemotherapy. Patients who had received bevacizumab–paclitaxel induction therapy and did not have progressive disease (PD) were randomized to maintenance therapy with endocrine therapy alone (group E) or endocrine plus capecitabine (1657 mg/m2/day on days 1–21, q4w) (group EC). In case of PD after maintenance therapy, patients received bevacizumab–paclitaxel reinduction therapy. Ninety patients were randomized. The median progression-free survival (PFS) under maintenance therapy (primary endpoint) was significantly longer in group EC (11.1 {95% CI, 8.0–11.8} months) than in group E (4.3 {3.6–6.0} months) (hazard ratio, 0.53; p < 0.01). At 24 months from the induction therapy start, the overall survival (OS) was significantly longer in group EC than in group E (hazard ratio, 0.41; p = 0.046). No difference was found in the time to failure of strategy (13.9 and 16.6 months in groups E and EC, respectively). Increased capecitabine-associated toxicities in group EC were tolerable. Addition of capecitabine to maintenance endocrine therapy may be a beneficial option after induction chemotherapy for HR-positive, HER2-negative AMBC patients.

Whole Body PET-CT In Management Of Lymphoblastic Lymphomas In Adults: Does It Have a Prognostic Impact?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4314-4314 ◽  
Author(s):  
Manju Sengar ◽  
Hasmukh Jain ◽  
Hari Menon ◽  
Sridhar Epari ◽  
Archi Agrawal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retrospective Analysis ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Mediastinal Mass ◽  
Bone Marrow Involvement ◽  
Post Induction ◽  
Mediastinal Radiation ◽  
Pet Ct

Abstract Introduction The two relevant questions that emerge and remains unanswered in the management of adult lymphoblastic lymphomas (LBL) are- how to select patients for mediastinal radiation and whom to subject for autologous transplant. Mediastinal radiation or intensification of therapy may reduce the mediastinal recurrence- a common site for relapse. It is also understood that not all patients with residual mediastinal mass relapse. The inability of computed tomography to differentiate between necrotic and viable disease in a residual mediastinal mass post induction therapy led us to explore PET-CT as modality to differentiate the same. In a retrospective analysis we evaluated the role of post-induction chemotherapy PET-CT in predicting the risk of relapse or progression in adult LBL patients. Methods In a single centre retrospective analysis we included newly diagnosed LBL patients (>15 years) who were treated with ALL- like therapy between January 2010 and February 2013. All patients who underwent PET-CT after induction chemotherapy were analysed. SUVmax was used to assess the response. Details of demographic variables, diagnosis, subtype, baseline LDH, bone marrow involvement, cerebrospinal fluid analysis, chemotherapy, radiotherapy, responses, relapse/progression, death and its cause and last follow up date were taken from electronic medical records. Results Twenty-two patients (17 males and 5 females) with median age 24.5 years (range, 16-44 years) were analysed. All patients had T- LBL. Thirteen patients (13/22) had stage IV disease (Ann Arbor stage) and all had bulky mediastinal mass at diagnosis. None of the patient had CSF or bone marrow involvement. Raised LDH and low albumin were present in 80% and 60% of patients respectively. Median WBC was 10,200/cumm (range, 4400-15300/cumm). All but 4 patients received BFM-90 ALL protocol based therapy. After induction 19 patients achieved complete remission on PET-CT. Patients who had residual mediastinal masses on PET-CT relapsed during later phase of therapy (all within 6 months) in mediastinum and died subsequently. Mediastinal radiation was given to one of these patients but it did not prevent a subsequent relapse. One patient who achieved complete response had bone marrow relapse after 16 months of therapy. Three patients had treatment related death (sepsis). At median follow up of 14 months 1-year overall survival was 69% and progression free survival was 78%. Conclusion Post induction therapy PET-CT seems to have prognostic role and may predict relapse for patients with residual disease activity. Such patients should be considered for treatment intensification. However, the role and timing of mediastinal radiation in such patients remains investigational. Disclosures: No relevant conflicts of interest to declare.

Lenalidomide Is a Highly Effective Maintenance Therapy in Myeloma Patients of All Ages; Results of the Phase III Myeloma XI Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1143-1143 ◽  
Author(s):  
Graham H Jackson ◽  
Faith E Davies ◽  
Charlotte Pawlyn ◽  
David A Cairns ◽  
Alina Striha ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Progression ◽  
Induction Therapy ◽  
Research Funding ◽  
Patient Choice ◽  
Phase Iii ◽  
Induction Treatment ◽  
Second Primary ◽  
Newly Diagnosed ◽  
Support Research

Abstract Background Lenalidomide is an effective treatment for myeloma and has been studied in a range of combination regimens worldwide. The results of these studies have suggested that prolonged exposure to lenalidomide is important to improve outcomes both as a maintenance agent post-transplant (Attal M et al NEJM 2012, McCarthy et al NEJM 2012) and in the transplant ineligible population (Palumbo A et al NEJM 2012, Benboubker L et al NEJM 2014). In the Myeloma XI study, the largest of its kind, we explored the use of oral lenalidomide continued to disease progression compared to no therapy in both newly diagnosed transplant eligible (TE) and transplant non-eligible (TNE) populations. Here we present the results of this maintenance randomization, which demonstrate the efficacy and safety of maintenance lenalidomide. Methods The Myeloma XI study is a Phase III, UK-based, multicenter, open-label, parallel group, randomized controlled trial for newly diagnosed symptomatic myeloma patients of all ages and includes a maintenance comparison of lenalidomide versus no maintenance. Newly diagnosed symptomatic myeloma patients both TE and TNE were enrolled to the study. Induction treatment in both pathways was with thalidomide or lenalidomide plus cyclophosphamide and dexamethasone, with appropriate dose reductions for TNE patients. TE patients proceded to a standard melphalan 200mg/m2 transplant. Patients were randomized to either maintenance lenalidomide or observation after achieving maximum response (TNE) or at 100 days after transplant (TE). Lenalidomide was administered at a dose of 10mg daily in 21/28 day cycles until disease progression. Dose adjustments for renal impairment and following AEs were permitted. The primary endpoints for the maintenance randomization were progression-free (PFS) and overall survival. Secondary endpoints included response, toxicity and PFS2. Time-to-event endpoints were measured from maintenance randomization. This abstract summarizes a preliminary analysis, final data will be presented at the meeting. The median follow up in this analysis is 26 months [IQR 12-41]. Results A total of 1550 patients, 828 TE and 722 TNE, median age 61 and 74 years, respectively, were randomized between lenalidomide (n=857) and no maintenance (n=693). The arms were well-balanced for clinical features and response to induction therapy (e.g. ISS stage III: 27% vs 23%, VGPR/CR: 73% vs 73%). The maintenance randomization has met its primary endpoint demonstrating a 55% reduction in risk of progression or death for lenalidomide compared to no maintenance (HR 0.45 [95%CI 0.39-0.52], median PFS 37 vs 19 months, p<0.0001) This significant improvement was observed in each pathway TE: HR 0.46 [95%CI 0.36-0.58], median PFS 60 vs 28 months, p<0.0001. TNE: HR 0.44 [95%CI 0.36-0.53], median PFS 26 vs 12 months, p<0.0001. The benefit of lenalidomide maintenance on PFS persisted across risk subgroups and was independent of induction therapy and response. An exploratory analysis of 132 patients stopping lenalidomide treatment for reasons other than disease progression (91 toxicity, 28 patient choice and 13 clinician choice) shows that patients receiving greater than 12 months of treatment have an improved median PFS compared to those stopping earlier (HR 0.35 [95%CI 0.18-0.68], 49 vs 31 months, p<0.0015). At this time 445 patients continue to receive lenalidomide maintenance on study. Of patients who have stopped therapy, only 21.5% did so due to toxicity. Relevant grade 3/4 adverse events were: neutropenia 35%, thrombocytopenia 7.4%, anaemia 4.4%, peripheral neuropathy 1.4%. Venous thromboembolism occurred in 2.3%. Second primary malignancy (SPM) data was collected and the relationship with maintenance therapy reviewed. 72 SPM were observed (24 no maintenance, 48 lenalidomide). Haematologic malignancy crude incidence was 0.3% vs. 0.9%. While we found a slight excess of SPM in older patients these were mostly non-invasive and did not impact the outcome benefit demonstrated. Conclusion The use of maintenance lenalidomide treatment results in highly significant improvements in PFS for patients of all ages and should be standard of care. On behalf of the NCRI Haem-Onc CSG Disclosures Jackson: Amgen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau. Davies:Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Pawlyn:Takeda Oncology: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel Support. Jones:Celgene: Honoraria, Research Funding. Kishore:celgene: Other: travel grant. Garg:Janssen: Other: Travel support, Research Funding, Speakers Bureau; Takeda: Other: Travel support; Novartis: Other: Travel support, Research Funding. Williams:Takeda: Honoraria, Other: Travel support, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria, Other: Travel support, Speakers Bureau; Celgene: Honoraria, Other: Travel support, Speakers Bureau. Karunanithi:Celgene: Other: Travel support, Research Funding; Janssen: Other: Travel support, Research Funding. Lindsay:Janssen: Consultancy; Novartis: Other: Travel support; Takeda: Other: Travel support; BMS: Consultancy, Other: Travel support; Celgene: Honoraria, Other: Travel support. Jenner:Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel support; Amgen: Consultancy, Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau. Kaiser:BMS: Consultancy, Other: Travel Support; Takeda: Consultancy, Other: Travel Support; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Chugai: Consultancy. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Owen:Takeda: Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Other: Travel support. Morgan:Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment; Celgene: Consultancy, Honoraria, Research Funding.

Rituximab Plus CHOP Followed by Maintenance Rituximab as Initial Therapy for Advanced Stage Indolent Non-Hodgkin’s Lymphoma (NHL); Initial Results of Induction Therapy in a Phase II Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4615-4615 ◽  
Author(s):  
Jane E. Huang ◽  
Lowell Hart ◽  
Jonathon Polikoff ◽  
Virginia Langmuir ◽  
Fan Zhang ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Phase Ii ◽  
Induction Therapy ◽  
Performance Status ◽  
Stage Iii ◽  
Induction Treatment ◽  
Advanced Stage ◽  
Serious Adverse Events ◽  
Ann Arbor ◽  
Initial Results

Abstract Background: This study was designed to investigate the activity and safety of rituximab (Rituxan®, R) plus CHOP induction therapy followed by maintenance R in patients with previously untreated advanced stage indolent NHL. The initial results of R-CHOP induction treatment are reported here. Methods: 102 patients with Ann Arbor Stage III or IV indolent NHL (follicle center/follicular grade I/II or nodal marginal zone B-cell by REAL; Type B or C by IWF) were enrolled into this open-label, multi-center, community-based, Phase II, single-arm trial. Patients received 6 cycles of standard R-CHOP induction therapy (cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, doxorubicin 50 mg/m2 all IV on Day 1; prednisone 100 mg/day Days 1–5). R 375 mg/m2 was given on Day 1 of each cycle except for cycle 1, when it was administered 2–3 days prior to CHOP chemotherapy. Subjects with an ongoing response (CR/CRu or PR) after induction receive maintenance R (4 weekly infusions) within 28 days after the completion of induction and repeated every 6 months for 2 years for a total of 16 maintenance R doses. The primary endpoints were CR/CRu after 6 cycles of induction and the incidence of R infusion-related toxicity during induction and maintenance therapy. Secondary endpoints included overall response rates (ORR), infusion times, serious adverse events (SAE) in induction and maintenance, and rituximab pharmacokinetics in maintenance therapy. Results: Baseline characteristics were: median age 57y (33.3% ≥60y); 40.2% female; ECOG performance status 0: 70.6%; Ann Arbor stage III: 28.4% and IV: 71.6%. Serum β2-microglobulin and LDH at baseline were above normal in 66.3% and 20.6%, respectively. CR/CRu at the end of induction in 102 patients was 51.0% (ORR 86.3%). 1% had progressive disease (PD) during induction. 2 subjects died during the induction period, both due to SAEs (probable pulmonary embolus, acute respiratory distress). SAEs occurred in 22.5% of subjects during induction with the most common event being febrile neutropenia (7.8%). Grade 3–4 R infusion-related toxicity occurred in 4.9% of patients in cycle 1; this decreased to 1% by cycle 2 of induction. Two subjects discontinued R for infusion-related toxicity. 44% of patients were able to receive their R dose within 3 hrs at cycle 2 and 69.2% of patients at cycle 6. Conclusion: Patients with advanced stage indolent NHL treated in the community setting with R-CHOP induction tolerate therapy well and have an excellent response rate. The outcomes of maintenance therapy and rituximab pharmacokinetics in maintenance await further follow-up.

Chemoradiation with FOLFOX plus cetuximab in locally advanced cardia or esophageal cancer: Final results of a GERCOR phase II trial (ERaFOX).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 8-8 ◽  
Author(s):  
G. Lledo ◽  
P. Michel ◽  
L. Dahan ◽  
L. Mineur ◽  
M. Galais ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Induction Therapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Caloric Intake ◽  
Stage Iv ◽  
Stage Design ◽  
Platinum Based Chemotherapy ◽  
Stage Iv Disease ◽  
Grade 3

8 Background: Chemoradiotherapy (CRT) for locally advanced cardia and esophageal cancer is based on 5-FU combined with cisplatin, which could be favorably replaced by oxaliplatin (Ox). Cetuximab (C) has demonstrated synergism with both radiotherapy (RT) and platinum-based chemotherapy. ERaFOX trial was evaluating the safety and efficacy of the addition of C to CRT with FOLFOX. Methods: Main inclusion criteria were: stage III squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction; WHO PS 0-1; age 18-80 years; weight loss <15% in the last 6 months. Patients (pts) received 2 cycles of FOLFOX induction therapy (Ox 85 mg/m2/d1, folinic acid 400 mg/m2/d1, 5-FU 2,400 mg/m2/d1-2, q2w) plus C (first infusion 400 mg/m2 then 250 mg/m2, q1w), then RT 50.4 Gy (1.8Gy/d x 28 fractions) with FOLFOX plus C (same doses, except 5-FU 1,800mg/m2/d1-2). Tumor evaluation was performed at the end of CRT (RECIST and endoscopic ultrasonography). The primary endpoint was overall response rate (ORR), with a 50% threshold for efficacy (Simon Minimax two-stage design). Results: From Nov 2007 to Feb 2010, 80 pts were enrolled in 12 centers. The characteristics of the 79 eligible pts were (1 ineligible pt for stage IV disease): male/female 60/19, median age 63 (23-79), PS 0/1/ND 47/31/1, squamous/adenocarcinoma/undifferentiated 53/25/1; esophagus/cardia 74/5; median daily caloric intake 1,720 Kcal (550-3160). 74 pts were treated by CRT (5 pts experienced anaphylaxis during the first cetuximab infusion). ORR (ITT) was achieved in 61 pts (77.2%), 6 pts (7.6%) had stable disease, and 9 pts (11.4%) had disease progression (3 pts were not evaluable). Grade 3-4 toxicities induction therapy/CRT were (%): neutropenia: 7.6/28.4; febrile neutropenia: 0.0/2.7; vomiting: 1.3/4.0; mucositis: 1.3/5.4; diarrhea: 3.8/2.7; dysphagia-esophagitis: 1.3/13.5; rash: 7.6/10.8; allergy 8.9/0.0. One toxic death (1.3%) occurred after CRT related to esophagitis with GI bleeding. Conclusions: Threshold for efficacy was reached with an ORR of 77.2%. Chemoradiotherapy with FOLFOX plus cetuximab is active and has an acceptable toxicity profile in patients with locally advanced cardia or esophageal cancer. No significant financial relationships to disclose.

ERCC1 as a predictor of response to induction therapy for stage III non-small cell lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18511-e18511
Author(s):  
Alessandro Marra ◽  
Dirk Kemming ◽  
Thomas Krueer ◽  
Ulrich Bosse ◽  
Maria Netchaeva ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mrna Expression ◽  
Induction Therapy ◽  
Tumor Regression ◽  
Stage Iii ◽  
Induction Treatment ◽  
Chemotherapy Response ◽  
Surgical Specimen ◽  
Platinum Based Chemotherapy ◽  
Ercc1 Expression

e18511 Background: Neoadjuvant platinum-based chemotherapy in stage III NSCLC offers the chance to eradicate occult metastases and decrease tumor volume, thus improving curative surgical resection rates. A remission after induction therapy is correlated with prolonged survival. However, only 40-50% of patients respond to therapy since there is still no validated predictor for the benefit of platinum based chemotherapy. As DNA repair mechanisms are related with resistance of lung cancer cells to platinum-based chemotherapy, aim of the study was to compare ERCC1 level in lymph node metastases with the degree of pathologic tumor regression after induction treatment and surgery. Methods: From July 2004 to June 2009, 46 NSCLC patients with clinically staged IIIA (N = 32) or IIIB (N = 14) NSCLC underwent at least two cycles of platinum-based induction chemotherapy and combined radio-chemotherapy. After restaging radical surgery was performed. ERCC1 was determined from pretreatment samples of metastatic nodes taken on mediastinoscopy. Real time RT-PCR assays were performed to determine ERCC1 mRNA expression. Tumor regression has been classified on surgical specimen using an score system ranging from grade I (pCR) to grade VI (non-responder). The samples were categorized into three groups according to their ERCC1 expression values and in two groups according to their chemotherapy response (either pCR or non-pCR). Results: A significant correlation between the ERCC1 expression level and the chance to achieve a pCR during a platinum-based chemotherapy could be demonstrated in our samples (P<0.05). Furthermore, the median overall survival in the pCR group was 44 vs. 29 month in the non-pCR group (HR 0.33 [95%-CI: 0.02-1.15]; P=0.06). However, no direct correlation between ERCC1 expression and local or distant metastasis formation could be found. Conclusions: Assessment of ERCC1 mRNA expression in pretreatment tumor tissue is feasible in the clinical setting and predicts response to platinum-based induction therapy. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to redefine induction protocols on an individual basis, thus enhancing response rates and perhaps outcome.

Improved Outcome of Childhood Acute Lymphoblastic Leukemia (ALL) with Induction Failure Treated on the Japan Association of Childhood Leukemia Study (JACLS) ALL F-Protocol.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1886-1886
Author(s):  
Nobuhiro Suzuki ◽  
Keiko Yumura-Yagi ◽  
Junichi Hara ◽  
Makoto Yoshida ◽  
Shinichiro Nishimura ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Survival Rate ◽  
Maintenance Therapy ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
The Other ◽  
Consolidation Therapy ◽  
Induction Failure ◽  
Improved Outcome

Abstract With modern risk-adapted multi-agent chemotherapy, complete remission (CR) is obtained in the majority of children with acute lymphoblastic leukemia (ALL) and long-term survival free from disease can be expected in more than 70% of them. However, the prognosis of the patients without CR (induction failure; IF) has been dismal. We conducted a prospective study of F-protocol followed by a hematopoietic stem cell transplantation (SCT) in patients with IF. Purpose: To evaluate the efficacy and safety of the treatment strategy adopted in the JACLS ALL F-protocol. Patients and methods: Between April 1997 and March 2005, 1,254 patients with newly diagnosed ALL (excluding mature B-cell ALL) were enrolled on two consecutive JACLS ALL protocols (ALL-97 and ALL-02). Excluding induction death, 19 (1.6%) out of 1,207 patients with non-Ph+ ALL and 9 (30%) out of 30 patients with Ph+ ALL could not achieve CR following four- or five-drug induction chemotherapy. Among them, 25 patients in total were entered the study with guardian’s written consent. F-protocol consisted of the AML oriented re-induction chemotherapy (3 days of 8 mg/m2 MIT, 500 mg/m2 CA, and 40 mg/m2 PSL, followed by 3 days of 200 mg/m2 VP16, CA, and PSL a week later), four block consolidation therapy consisting of two alternative regimens A and B (A: HD-DEX, VP16, CA, MIT, B: HD-MTX, ASP, PSL, CA, THP-ADR) and maintenance therapy. Patients with CR were scheduled to receive SCT after the second consolidation therapy before the maintenance therapy. Transplant procedures depended on the institute. Results: Following the re-induction therapy, 15 of 16 patients with non-Ph+ ALL (93.8%) achieved CR and 13 (86.7%) of them had continued CR until 27th week of treatment (CCR), which was the expected limiting time of SCT. Eight of 11 patients receiving SCT at the first CCR are alive. Two of 13 patients with CCR did not receive SCT by a physician’s decision, and relapsed during maintenance therapy. However they are alive following SCT in second CR. Five-year overall survival rate (OS) and event free survival rate for all 16 cases was 53% and 32.8%, respectively. Estimated five-year OS for patients receiving SCT at the first CCR was 59.7%. On the other hand, only 3 of 9 patients with Ph+ ALL (33.3%) achieved CR. No patients without response to re-induction therapy could achieve CR by any subsequent chemotherapy, but one success with SCT. Among 3 patients attaining a CR with re-induction therapy, 2 could continue CR and underwent SCT. One is alive in CCR and the other deceased from TRM. The other patient, relapsed during consolidation therapy, underwent SCT with success. Five-year OS for all 9 patients with Ph+ ALL was 33.3%. Concerning about adverse events of F-protocol, there was only one non-hematological toxicity NCI-CTC grade 4, which was pancreatitis due to ASP. Conclusions: F-protocol could produce a high remission induction rate in non-Ph+ ALL, but not in Ph+ ALL. Improved outcome of non-Ph+ ALL patients with IF seemed to be obtained with F-protocol timely followed by SCT.

Results of an AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Randomized Clinical Trial in Children with Low- and Intermediate-Risk Relapsed Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 65-65
Author(s):  
Franco Locatelli ◽  
Marco Zecca ◽  
Gianni Cazzaniga ◽  
Luciana Vinti ◽  
Andrea Biondi ◽  
...  
Keyword(s):  
T Cell ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Continuous Treatment ◽  
Unrelated Donor ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Line Therapy ◽  
To Receive

Abstract Leukemia recurrence remains the main cause of treatment failure in children with ALL. The prognosis of children with relapsed ALL is strongly influenced by the site of relapse, time elapsing between diagnosis and recurrence and by blast cell immune-phenotype. Recently, several groups reported probabilities of disease-free survival (DFS) in the order of 60% for children with low/intermediate-risk ALL in 1st relapse using different approaches. Despite this remarkable progress, the best re-induction and consolidation treatment remains to be defined. We, thus, conducted from 10/2003 to 06/2012 a multicenter randomized trial aimed at comparatively evaluating the efficacy of 2 alternative approaches in centers affiliated to the Italian AIEOP network. Included in the study were patients below the age of 18 experiencing late (i.e. more than 6 months from treatment discontinuation) isolated extramedullary (IEM) relapse (S1 patients, #22) or children with B-cell precursor (BCP)-ALL who had early (i.e. between 18 months from diagnosis and 6 months after completion of front-line treatment) or late combined bone marrow (BM) relapse, late isolated BM relapse of BCP–ALL, and very early (i.e. within 18 months from diagnosis) or early IEM of either BCP-ALL or T-cell ALL (S2 patients, # 255). S2 children were randomized to receive induction therapy consisting of either two multiagent chemotherapy courses, F1 and F2 (ARM-A), according to the ALL-REZ BFM P95/96 trial, or a classical 4-drug continuous reinduction therapy (protocol I-A-IDA, ARM-B). After induction, ARM-A patients were given a continuous treatment element including idarubicin (Protocol II-IDA), followed by 5 additional alternating R1/R2 courses and maintenance therapy (24 months). After induction therapy, ARM-B patients received 8 additional alternating R1/R2 courses and maintenance therapy (24 months, see Figure 1). S1 patients received ARM-A treatment with the exception of only 3 alternating R1/R2 consolidation courses and shorter maintenance therapy (12 months). All S2 children with an available HLA-identical sibling were candidate to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT), while those relapsing within 48 months from diagnosis were eligible to receive the allograft also from an unrelated donor (UD) of BM cells or a suitable UD cord blood unit. For S1 patients, both autologous (auto) and allo-HSCT were considered acceptable post-remissional options; auto-HSCT was also employed in a minority of S2 children relapsing more than 48 months from diagnosis. Of the whole cohort of children, 143 were males and 134 were females; median age at diagnosis and at time of relapse was 5 (range 0.2-17) and 9 (range 1.1-17.9) years, respectively. Among the 255 S2 patients, 127 were allocated to ARM-A and 128 to ARM-B. All S1 children obtained a 2nd complete remission (CR), while the probability of reaching 2nd CR of S2 patients was similar in the 2 randomization arms (95% vs 96%). The 6-year DFS for the 22 S1 children was 75% (confidence interval, CI, 55-94); 13 of these children were given either auto-HSCT (#7) or allo-HSCT (#6), while 9 were treated with chemotherapy only. The 6-year DFS for the 255 S2 children was 65% (CI 57-72); the DFS for ARM-A and ARM-B patients was 60% (CI 48-71) and 69% (CI 60-79), respectively (p=ns). Among S2 patients, 179 received allo-HSCT either from an HLA-identical sibling (#51) or a BM/CB UD (#105) or an HLA-partially matched relative (#23) after T-cell depletion of the graft (TCD haplo-HSCT). Of the remaining 76 children, 12 were given auto-HSCT, while 64 received chemotherapy only. The 6-year DFS for S2 children who did or did not receive allo-HSCT was 66% (CI 58-74) and 58% (CI 38-77), respectively (p=ns). Among allo-HSCT recipients, the 6-year DFS was 59% (CI 42-75), 72% (CI 62-82) and 62% (CI 41-83) for children given HLA-identical sibling, UD or TCD haplo-HSCT, respectively (p=ns). Altogether, these results confirm that a high proportion of children with low-/intermediate-risk relapsed ALL can be rescued by second line therapy, including transplantation. A re-induction course similar to that employed in first-line therapy is as effective as that proposed in the ALL-REZ BFM P95/96 trial. UD-HSCT and TCD haplo-HSCT are suitable and effective alternatives for children candidate to an allograft but lacking an HLA-identical sibling. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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