Efficacy of Biofeedback Therapy in Clinical Practice for the Management of Chronic Constipation and Fecal Incontinence

Abstract Background Chronic constipation (CC) and fecal incontinence (FI) are often secondary to pelvic floor neuromuscular sensory or motor dysfunction. Biofeedback therapy (BFT) uses visual and verbal feedback to improve anorectal coordination, strength and sensation. In clinical trials, BFT demonstrated response rates between 70% and 80%. The purpose of this study is to determine the effectiveness of BFT in clinical practice. Methods In this retrospective observational cohort study, the charts of all patients who completed BFT at our centre were reviewed. A positive response to BFT was defined as improvement in ARM profile from baseline or subjective symptom improvement or both. Descriptive statistics were used to analyze the data. Results One hundred thirty patients with an average age of 57.5 ± 16.4 years and 79.2% female were included. Of all patients, 43.1% were referred for CC, 37.7% for FI, 16.9% for alternating CC and FI, and 2.3% for rectal pain. The overall response rate to BFT was 76.2% (n=99). Of those that responded, 64.6% (n=64) demonstrated both ARM and symptom improvement, 27.3% (n=27) had ARM improvement but no symptom improvement, and 8.1% (n=8) had symptom improvement but no ARM improvement. In patients with FI, the overall response rate was 79.6% (n=39) with symptom improvement in 67.3% (n=33). In those with CC with dyssynergic defecation (n=53), the overall response rate was 69.8% (n=37); however, only 45.3% (n=24) had symptomatic improvement. Conclusion In our clinical practice, although overall response rates to BFT are similar to published reports, patients with CC with dyssynergic defecation are less likely to have symptomatic response compared with those with FI.

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The Effects of a Between-Wave Incentive Experiment on Contact Update and Production Outcomes in a Panel Study

Journal of Official Statistics ◽

10.2478/jos-2013-0022 ◽

2013 ◽

Vol 29 (2) ◽

pp. 261-276 ◽

Cited By ~ 6

Author(s):

Katherine A. McGonagle ◽

Robert F. Schoeni ◽

Mick P. Couper

Keyword(s):

Data Collection ◽

Overall Response Rate ◽

Response Rate ◽

Panel Study ◽

Response Rates ◽

Income Dynamics ◽

Overall Response ◽

Percentage Points ◽

Contact Information ◽

The U.S

Abstract Since 1969, families participating in the U.S. Panel Study of Income Dynamics (PSID) have been sent a mailing asking them to update or verify their contact information in order to keep track of their whereabouts between waves. Having updated contact information prior to data collection is associated with fewer call attempts, less tracking, and lower attrition. Based on these advantages, two experiments were designed to increase response rates to the between wave contact mailing. The first experiment implemented a new protocol that increased the overall response rate by 7-10 percentage points compared to the protocol in place for decades on the PSID. This article provides results from the second experiment which examines the basic utility of the between-wave mailing, investigates how incentives affect article cooperation to the update request and field effort, and attempts to identify an optimal incentive amount. Recommendations for the use of contact update strategies in panel studies are made.

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Comparing the Cost Per Treatment Success of Thrombopoietin Receptor Agonists to Watch & Rescue for the Treatment of Primary Adult Chronic Immune Thrombocytopenia (ITP) in the US

Blood ◽

10.1182/blood.v120.21.4640.4640 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4640-4640

Author(s):

Kelly Northridge ◽

Mark Danese ◽

Robert Deuson

Keyword(s):

Overall Response Rate ◽

Response Rate ◽

Treatment Success ◽

Response Rates ◽

Thrombopoietin Receptor Agonists ◽

Overall Response ◽

Platelet Counts ◽

Receptor Agonists ◽

Thrombopoietin Receptor ◽

The Us

Abstract Abstract 4640 OBJECTIVES: To compare the drug costs relative to response of two thrombopoietin receptor agonists, romiplostim and eltrombopag, to Watch & Rescue for the treatment of chronic immune thrombocytopenia (ITP), from a health plan perspective. ITP, a diagnosis of exclusion, is characterized by low platelet counts and, depending on platelet count level, increased risk of bleeding (Rodeghiero F, et al. Blood. 2009:113(11):2386–2393). METHODS: An Excel® model compared 2011 US drug costs (wholesale acquisition cost) to the overall patient response rates (four or more weekly platelet counts of ≥50 × 109/L during the study from week 2 to 25) observed in individual 6-month placebo-controlled trials for romiplostim, eltrombopag, and placebo (or Watch & Rescue) (http://www.nice.org.uk/nicemedia/live/12025/50715/50715.pdf). These trials studied patients with median baseline platelet counts of 16 × 109/L (in both the romiplostim and eltrombopag trials) with 51% of the eltrombopag and 64% of the romiplostim patients receiving ≥3 previous treatments prior to joining each respective trial (Kuter, D, et al. Lancet. 2008:371:395–403; Cheng G, et al. Lancet. 2011:377:393–402; Bussel, J, et al. Lancet. 2009:373:641–648). The model considers a 55 mg daily dose of eltrombopag, and an average dose (including wastage) derived from a trial-based simulation for the US of 286 mcg per weekly administration of romiplostim. It assumes that 30% of US patients are splenectomized. The model considers a 1 g/kg overall dose of IVIg per rescue event at an average romiplostim trial-based weighted average (by splenectomy status) rate of 2.29 administrations per 6-month period (Weitz, I, et al. Curr Med Res Opin. 2012:28(5):789–796). RESULTS: For romiplostim patients, the expected cost of treating a patient with romiplostim over a 6-month period (trial period) is $34,655, with an overall response rate of 83%, or a cost per patient with an overall response of $41,753 ($34,655÷83%). The expected 6-month cost of treating the same patient with eltrombopag is $28,516, for an overall response rate of 57%, or a cost per patient with an overall response of $50,028 ($28,516÷57%). Comparatively, the expected 6-month cost of treating the same patient with Watch & Rescue is $11,681, with an overall response rate of 9%, or a cost per patient with an overall response of $129,789 ($11,681÷9%). Patients treated with thrombopoietin receptor agonists experience a 48 to 74% higher overall response rates than patients treated with Watch & Rescue, at a 153 to 196% reduction in resources to achieve the response. Sensitivity analyses were performed on key variables; a ±50% change in the average 6-month cost of IVIg (from either a decrease in cost or a decrease in the average number of administrations) resulted in ±50% change in the Watch & Rescue cost per response ($64,894 to $194,683). A decrease of 25% to the response rates for romiplostim and eltrombopag individually resulted in a 33% increase in the overall cost per patient with an overall response to $55,670 for romiplostim and $66,704 for eltrombopag. CONCLUSIONS: In chronic adult ITP, the use of thrombopoietin receptor agonists represents an efficient use of healthcare resources, with better health outcomes at a significantly lower cost per treatment success than treatment with Watch & Rescue. Disclosures: Northridge: Amgen Inc.: Consultancy, Research Funding. Danese:Amgen Inc.: Consultancy, Research Funding. Deuson:Amgen Inc.: Employment, Equity Ownership.

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Up-Front Treatment of Diffuse Large-B Cell Lymphoma (DLBCL) in Elderly Patients with Rituximab in Combination with CHOP-Like Chemotherapy: A Multicenter Study on the Current Clinical Management.

Blood ◽

10.1182/blood.v106.11.4778.4778 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4778-4778 ◽

Cited By ~ 1

Author(s):

Miguel A. Canales ◽

Javier de la Serna ◽

Pilar Sabin ◽

Joaquin Diaz-Mediavilla ◽

Mariano Provencio ◽

...

Keyword(s):

Overall Survival ◽

Clinical Practice ◽

Adverse Events ◽

Elderly Patients ◽

Overall Response Rate ◽

Response Rate ◽

B Cell Lymphoma ◽

Overall Response ◽

Significant Difference

Abstract Based on results of GELA study, rituximab in combination with CHOP chemotherapy, given for eight cycles, may be considered the new standard of care for patients older than 60 years diagnosed with DLBCL. However, the afraid of early toxicity and underlying co-morbid illness in elderly patients implies often adjustments in this scheme. The aim of this study was to analyze the routine clinical practice in the up-front treatment of elderly patients (>65 years) with DLBCL. We have enrolled onto this study 80 patients (48 females) with median age 74 years (range, 65 to 85 years) who have been treated with CHOP-like regimens in combination with rituximab as first-line therapy. The 75% of patients had ECOG 0-1, 81% had Ann-Arbor stage III-IV, 41% had B-symptoms, 59% had aIPI 2-3, 39% had bulky disease (> 7 cm) and 55% had elevated beta-2 microglobulin. The most of patients received as up-front therapy R-CHOP (89%); R-CNOP and R-CEOP (doxorubicin is substituted for mitoxantrone and epirubicin, respectively) were the alternative regimens administered. The 57.5% of patients received 6 courses of treatment; the 25% received less than 6 cycles and only the 6% of patients (5 out of 80 patients) received 8 courses of treatment. In 31 out of 80 patients the doses of chemotherapy was reduced; in 20 patients the doses of chemotherapy were reduced in all courses and 2 patients received reduced doses of chemotherapy in 5 out of 6 cycles. In the 40% of patients G-CSF have been administered. The overall response rate was 86% (72% CR/CRu, 14% PR). In the 22 patients who received the lower doses of chemotherapy the overall response rate was 82% (50% CR/CRu) versus 88% in the remaining patients (81% CR/CRu) (p<0.05). Adverse events were observed in the 47.5% of patients and neutropenia was the most frequent complication. In those patients who received reduced doses of chemotherapy less adverse events were observed (13.6% versus 60.3%, p<0.001). With a median follow-up of 15 months, the event-free survival in the assessable population has not been reached (60% at 2 years) and there was no significant difference in those patients who have received the reduced doses of chemotherapy (median 18.5 months versus not reached). The median overall survival has not been reached. At 2 years overall survival is 73% in the entire population and 51% in patients receiving the reduced doses of chemotherapy compared to 80% in the remaining patients but the difference was not statistically significant. In conclusion, in our current clinical practice, 6 courses of chemotherapy (CHOP-like) in combination with rituximab is the commonest regimen used for the treatment of elderly patients. The administration of reduced doses of chemotherapy is associated with both a significant decrease in adverse events and complete response rates and may be translated into a shorter event-free and overall survival. A longer follow-up may be necessary to reveal this difference. Logically, randomized trials are mandatory to address differences between 6 and 8 courses of immunochemotherapy in this population.

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Randomized Double-Blind Clinical Trial Comparing Safety and Efficacy of the Biosimilar BCD-021 with Reference Bevacizumab

10.21203/rs.3.rs-763106/v1 ◽

2021 ◽

Author(s):

Daniil Stroyakovskiy ◽

Natalya Fadeeva ◽

Marina Matrosova ◽

Konstantin Shelepen ◽

Grigoriy Adamchuk ◽

...

Keyword(s):

Clinical Trial ◽

Overall Response Rate ◽

Response Rate ◽

Response Rates ◽

Phase Iii ◽

Occurrence Rate ◽

Study Endpoint ◽

Primary Study ◽

Overall Response ◽

The Difference

Abstract Background BCD-021 is a bevacizumab biosimilar which was shown to be equivalent to reference bevacizumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to compare efficacy and safety of BCD-021 and reference bevacizumab in combination with paclitaxel and carboplatin in a first-line treatment of inoperable or advanced non-squamous non-small-cell lung cancer (NSCLC). Methods Patients with no previous treatment for advanced non-squamous NSCLC were randomly assigned 3:2 to BCD-021 or reference bevacizumab and were treated with bevacizumab + paclitaxel + carboplatin. Therapy continued for 6 cycles (every 3 weeks), until progression of the disease or unbearable toxicity. The primary study endpoint was the overall response rate. The study goal was to prove the equivalent efficacy of BCD-021 and reference bevacizumab. Equivalence margins for 95% CI for the difference in the overall response rates were set at [-18%; 18%], for 90% CI for the ratio of overall response rate were set at [67%; 150%]. Results In total 357 patients were enrolled in the study, 212 in the BCD-021 group and 145 in the reference bevacizumab group. The ORR was 34.63% in the BCD-022 group and 33.82% in the reference bevacizumab group. Limits of 95% CI for the difference in overall response rates between the groups were [-9.47%; 11.09%]. Limits of 90% CI for the ratio of overall response rate between the groups were [79.6%; 131.73%]. For both approaches CI lied within predetermined equivalence margins. Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86.89% of patients in BCD-021 group and 89.05% of patients in reference group). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding anti-drug antibody occurrence rate was found between BCD-022 (n = 4; 1.96%) and comparator (n = 5; 3.65%). Both drug products showed low occurrence rate and short life of anti-bevacizumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures. Conclusions Thus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug. Trial registration: The trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013).

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Escalation Treatment Algorithm with Bortezomib, Dexamethasone and Bendamustine for Patients with Relapsed or Refractory Multiple Myeloma: A Singel Centre Experience.

Blood ◽

10.1182/blood.v108.11.3540.3540 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3540-3540 ◽

Cited By ~ 1

Author(s):

Roland Fenk ◽

Mark Michael ◽

Fabian Zohren ◽

Thorsten Graef ◽

Arkosch Czibere ◽

...

Keyword(s):

Multiple Myeloma ◽

Disease Progression ◽

Overall Response Rate ◽

Response Rate ◽

Treatment Algorithm ◽

Response Rates ◽

Treatment Schedule ◽

Prognostic Parameters ◽

Minor Response ◽

Overall Response

Abstract Bortezomib has improved the outcome of patients with multiple myeloma. Nevertheless, bortezomib monotherapy achieves responses in less than 50% of patients with advanced disease. Combination therapy can improve response rates but is associated with more adverse events such as neuropathy or myelosuppression. Therefore, we evaluated a step-wise escalation treatment algorithm for patients with relapsed or refractory myeloma. The initial treatment (step1) consisted of bortezomib monotherapy (1.3mg/m2 on day 1,4,8,11). Patients who did not show a at least 25% reduction of paraprotein at the beginning of cycle 2 received an escalated treatment (step2) with bortezomib and dexamethasone (40mg on day 1,4,8,11). The next treatment escalation (step3) was performed by addition of bendamustine (50–100mg/m2 on day 1 + 8) to bortezomib and dexamethasone. Step3 was used for patients who did respond with less than a minor response to one cycle of step2 treatment. We report on 48 patients who have been treated at our institution according to this regimen. Patients median age was 59 years with a median β2-microglobuline level of 3.8 g/dl and median albumine level of 3.7 g/dl. All patients were heavily pre-treated with in median three prior treatment regimen including high-dose therapy and thalidomide in more than 90% of patients. Escalation therapy was applied as planned to 36 (75%) patients, whereas 12 (25%) patients received step2 at the beginning of treatment due to physicians decision because of fulminant disease progression with hypercalcemia or severe tumor burden. Toxicity was as expected for bortezomib monotherapy and was manageable with escalated treatment steps. Response rates for patients in step1 were 11% nCR, 36% PR and 11% MR. In step2 (n=26) response rates were 31% PR, 15% MR and in step3 (n = 7) 43% PR and 29% MR. This results in an overall response rate of 80% for all patients. Patients with fulminant progressive disease who needed upfront treatment with step2 had an inferior overall response rate of 42% in comparison to 90% for patients who were treated according to the planned treatment schedule. With a median follow-up of 26 months the median time to progression and overall survival was 9 months and not reached for patients in the planned program and 2 and 4 months for the patients with upfront escalated therapy. Univariate analysis including several conventional prognostic parameters revealed physicians decision for upfront escalated treatment and age >60 years as the only bad prognostic factors. Interestingly, for patients within the planned treatment schedule, response to previous therapies, the extent of paraprotein reduction and the required escalation step had no impact on response duration. Another interesting observation of our single center study was that re-exposure of step3 treatment at the time of relapse (n=8) resulted in a new remission in 50% and in stable disease in 38% of patients. In conclusion, escalating therapy with bortezomib, dexamethasone and bendamustine induces durable remissions in the majority of patients, even in the presence of poor prognostic parameters. However, this treatment algorithm is not applicable for patients presenting with fulminant disease progression, as these patients need more aggressive regimens.

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Cisplatin in the treatment of recurrent childhood primary brain tumors.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.1.62 ◽

1988 ◽

Vol 6 (1) ◽

pp. 62-66 ◽

Cited By ~ 89

Author(s):

R W Walker ◽

J C Allen

Keyword(s):

Brain Tumors ◽

Germ Cell ◽

Germ Cell Tumor ◽

Overall Response Rate ◽

Response Rate ◽

Cell Tumor ◽

Primitive Neuroectodermal Tumors ◽

Primary Brain Tumors ◽

Overall Response ◽

Neuroectodermal Tumors

Thirty-three patients were treated with intravenous (IV) cisplatin (CPDD) of whom 32 were considered evaluable. There were 14 medulloblastomas, five primitive neuroectodermal tumors (PNET), nine gliomas, three ependymomas, and one germ cell tumor. The overall response rate was 13 of 32 (41%). Eleven responses (five complete [CR], five partial [PR], one mixed [MR]) were noted in the patients with medulloblastoma. The response rate within this group was 79%. Toxicity was tolerable, although it precluded further therapy in five patients.

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Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) for Tinnitus: A Retrospective Study

Ear Nose & Throat Journal ◽

10.1177/01455613211016896 ◽

2021 ◽

pp. 014556132110168

Author(s):

Haidi Yang ◽

Gui Cheng ◽

Zhengrong Liang ◽

Wenting Deng ◽

Xiayin Huang ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Overall Response Rate ◽

Response Rate ◽

Repetitive Transcranial Magnetic Stimulation ◽

Subjective Assessment ◽

Overall Response ◽

Duration Of Disease ◽

Vas Scores ◽

Assessment Result

Objective: Current studies still find insufficient evidence to support the routine use of repetitive transcranial magnetic stimulation (rTMS) in tinnitus. This study aimed to assess response of tinnitus to treatment with rTMS and identify factors influencing the overall response. Methods: Between January 2016 and May 2017, 199 tinnitus patients were identified from a retrospective review of the electronic patient record at the Sun Yat-sen Memorial Hospital. All patients received rTMS treatment. Their clinicodemographic profile and outcomes, including the tinnitus handicap inventory (THI) and visual analog scale (VAS) scores, were extracted for analysis. Results: Regarding the THI results, 62.3% of all patients responded to rTMS. The analysis of the VAS score revealed an overall response rate of 66.3%. Both percentages were close to the patient’s subjective assessment result, of 63.8%. Patients with tinnitus of less than 1-week duration had the highest response rate to rTMS in terms of either THI/VAS scores or the patient’s subjective assessment of symptoms. Tinnitus duration was recognized as a factor influencing the overall response to the treatment. Conclusions: Repetitive transcranial magnetic stimulation treatment is effective for patients with tinnitus, but its efficacy is affected by tinnitus duration. Tinnitus patients are advised to attend for rTMS as soon as possible since therapy was more effective in those with a shorter duration of disease of less than 1 week.

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Combination of trastuzumab, pertuzumab and docetaxel in patients with advanced non-small cell lung cancer (NSCLC) harboring HER2 mutation: Final results from the IFCT-1703 R2D2 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9015 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9015-9015

Author(s):

Julien Mazieres ◽

Claire Lafitte ◽

Charles Ricordel ◽

Laurent Greillier ◽

Jean-Louis Pujol ◽

...

Keyword(s):

Brain Metastases ◽

Overall Response Rate ◽

Advanced Nsclc ◽

Response Rate ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Loading Dose ◽

Overall Response ◽

Grade 3 ◽

Exon 20

9015 Background: Human epidermal growth factor receptor 2 ( HER2) exon 20 insertions and mutations are oncogenic drivers found in 1-2% of NSCLC. However, there are no approved therapies for these patients. Many studies suggest that the use of HER2 inhibitors developed for breast cancer patients might be of interest in this setting. The aim of this trial was to prospectively evaluate the interest of a combination of two antibodies against HER2 (trastuzumab and pertuzumab) with docetaxel. Methods: IFCT-1703 R2D2 trial is a multicenter, non-randomized phase 2 study with a two-stage design, a power of 90% and an alpha risk at 5% (one-sided). HER2 mutational status was assessed locally in certified molecular genetic centers. Main other inclusion criteria were advanced NSCLC, progression after ≥ 1 platinum-based chemotherapy, asymptomatic brain metastases, left ventricular ejection fraction (LVEF) ≥ 50%, and PS 0-2. Patients were treated every 3 weeks with pertuzumab at a loading dose of 840 mg, and 420 mg thereafter; plus trastuzumab at a loading dose of 8 mg/kg and 6 mg/kg thereafter; and docetaxel at 75 mg/m². Treatment was given until toxicity or disease progression. The primary outcome was overall response rate (ORR). Other endpoints included duration of response, progression-free survival and safety. NCT number: NCT03845270. Results: From May 2019 to October 2020, 45 patients were enrolled in 17 centers and received study treatment. Median age was 64.5 years (range 31–84), 72% females, 35% smokers, 100% non-squamous histology and 15% with ECOG PS 2. 31.1% patients had brain metastases. PD-L1 was expressed ≥ 1% and ≥ 50% in 36% and 7% of the patients, respectively. No other oncogene driver was found associated with HER2 exon 20 mutation. With a median follow-up of 12 months, 44 (98%) patients were evaluable for the primary endpoint. Overall response rate was 29% (n = 13), stable disease 56% (n = 26). Median PFS was 6.8 months (95% CI[4.0-8.5]). Median duration of treatment in patients with confirmed response (n = 13) was 10 months (95% CI[2.7-14.9]). At the time of data cut-off, 15 patients (33%) were still under treatment. Grade 3/4 treatment-related adverse events (AEs) were observed in 64% of patients. No patient experienced treatment discontinuation because of toxicity. One sudden death was possibly related to treatment. Most frequent grade ≥ 3 AEs were neutropenia (33%), diarrhea (13%) and anaemia (9%). Grade 1/2 dyspnea was observed in 3 (6.7%) patients. No ILD were reported. Variation LVEF was -1.72% on average (min: -18 %; max: 10 %). Conclusions: The triplet trastuzumab, pertuzumab and docetaxel is feasible and active in HER2 pretreated advanced NSCLC. These results confirm the activity of HER2 antibodies-based strategy which should be considered in these patients. Clinical trial information: NCT03845270.

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Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

Blood Advances ◽

10.1182/bloodadvances.2020002583 ◽

2020 ◽

Vol 4 (17) ◽

pp. 4091-4101

Author(s):

Arne Kolstad ◽

Tim Illidge ◽

Nils Bolstad ◽

Signe Spetalen ◽

Ulf Madsbu ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Overall Response Rate ◽

Response Rate ◽

Phase 1 ◽

B Cell Lymphoma ◽

Complete Response ◽

Hematologic Toxicity ◽

Overall Response ◽

Non Hodgkin Lymphoma ◽

Anti Cd20

Abstract For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20–based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the “cold” anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

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Phase I study of the combination of fludarabine, mitoxantrone, and dexamethasone in low-grade lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.3.575 ◽

1994 ◽

Vol 12 (3) ◽

pp. 575-579 ◽

Cited By ~ 69

Author(s):

P McLaughlin ◽

F B Hagemeister ◽

F Swan ◽

F Cabanillas ◽

O Pate ◽

...

Keyword(s):

Overall Response Rate ◽

Response Rate ◽

Single Agent ◽

Active Agent ◽

Large Cell ◽

Maximum Tolerated Dose ◽

Low Grade ◽

Overall Response ◽

Nonhematologic Toxicity ◽

High Fraction

PURPOSE Fludarabine is an active agent for patients with low-grade lymphoma (LGL) but has mainly been used as a single agent. This trial was designed to define the maximum-tolerated dose (MTD) of a combination of fludarabine, mitoxantrone, and dexamethasone (FND), to identify the toxicities of these agents in combination, and to make preliminary observations about the efficacy of this combination. PATIENTS AND METHODS Twenty-one patients with recurrent LGL or follicular large-cell lymphoma were treated, in cohorts of three, at stepwise escalating doses. Patients were required to have adequate marrow function and normal renal, hepatic, and cardiac function. RESULTS The MTD of the combination was found to be as follows: fludarabine, 25 mg/m2/d (days 1 to 3); mitoxantrone, 10 mg/m2 (day 1); and dexamethasone, 20 mg/d (days 1 to 5). Each course was administered monthly, and up to eight courses were given. Dose-limiting toxicities were neutropenia and infections. Thrombocytopenia was modest. Nonhematologic toxicity was very modest. Responses were seen at every dose level. The overall response rate was 71%, with a 43% complete remission (CR) rate. The median duration of CR was 18 months (with follow-up duration from 13 to 28+ months). CONCLUSION FND was well tolerated in this population. While our primary aim was to define the MTD, our preliminary observations on the efficacy of the regimen were favorable. The overall response rate was high, there was a high fraction of CRs, and our early impression is that these responses are durable.

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