Artemether–lumefantrine and dihydroartemisinin–piperaquine treatment outcomes among children infected with uncomplicated Plasmodium falciparum malaria in Mwanza, Tanzania

Abstract Background Artemisinin based combination therapies (ACTs) have been a cornerstone in the treatment of malaria in the world. A rapid decline in dihydroartemisinin piperaquine (DHP) and artemether lumefantrine (ALU) efficacies has been reported in some parts of South East Asia, the historical epicenter for the antimalarial drug resistance. Prolonged drug use is associated with selection of resistant parasites due to exposure to inadequate drug levels hence effects on treatment outcomes in malaria. ALU and DHP are used as first line and alternative first line, respectively, in Tanzania. This study was carried in Igombe, Tanzania to assess the efficacies of ALU and DHP in routine treatment of uncomplicated malaria among children. Methods This was a prospective study involving children up to 10 years and followed up for 28 and 35 days as per the WHO protocol, 2015 for monitoring antimalarial drug efficacy. The primary end points were crude and adjusted Adequate Clinical and Parasitological Response (ACPR), parasite clearance rate and reported adverse events. Results A total of 205 children with uncomplicated malaria were enrolled. One hundred and sixteen participants were treated with ALU, while 89 participants were treated with DHP. Two participants in the ALU group were lost within the 24 h of follow-up. The PCR unadjusted ACPR was108 (94.7%) for ALU and 88 (98.9%) for DHP, while the PCR adjusted ACPR was 109(95.6%) and 88(98.9%) for ALU and DHP, respectively, at 28 day follow-up. No treatment failure was observed in both groups. Cumulative risk of recurrent parasitemia was similar in both groups (p = 0.32). Age and parasite density were strong predictors for persistent day 1 parasitemia (p = 0.034 and 0.026, respectively). Nausea and vomiting, abdominal pain and headache were the most clinical adverse events reported in both groups of patients. Conclusion The present study shows that ALU and DHP are still efficacious after more than a decade of use with PCR corrected efficacies greater than 95% implying a failure rate less than 5% which is below the WHO minimum threshold requirement for recommendation of a change in the treatment policy. Both drugs were well tolerated with no major adverse events reported.

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Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade of its use in Kenya

10.21203/rs.3.rs-22339/v1 ◽

2020 ◽

Author(s):

Gabriel M. Kishoyian ◽

Eliud N. M. Njagi ◽

George O. Orinda ◽

Francis T. Kimani ◽

Kevin Thiongo ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Uncomplicated Malaria ◽

Standard Dose ◽

Parasite Clearance ◽

First Line ◽

Study Population ◽

Treatment Responses ◽

Lost To Follow Up ◽

Line Drug

Abstract Background: Plasmodium falciparum resistance to antimalarial drugs remains to be a major threat to the control of malaria globally. After the deployment of artemisinin-based combination therapy (ACT), there have been reports of reduced sensitivity of the drug to parasite clearance. In Kenya, artemisinin-lumefantrine (AL) is the recommended first-line drug in the treatment of uncomplicated malaria. This study sought to assess the efficacy of AL after its reintroduction in Kenya, a decade later. In this study, we assessed clinical and parasitological responses of children under five years in May and November 2015 in Chulaimbo sub-County, Kisumu, Kenya.Method: Patients of ≥6 and ≤60 months of age with confirmed Plasmodium falciparum mono-infection were enrolled in the study. The patients were treated with a standard dose of AL and followed up for 28 days. During which period we monitored treatment responses and follow-up adherence.Results: Of the 90 patients enrolled, fourteen (14) were lost to follow-up, with 76 completing the study period. Seventy-five patients 75 (98.7%) cleared, parasitemia within 48 hours while one (1.3%) cleared on day 3. There was 100% clinical and parasitological parasite clearance. Conclusion: Artemisinin lumefantrine was found to be highly efficacious to plasmodium falciparum parasites in children aged ≥6 and ≤60 months. Based on this, the drug can be used to treat uncomplicated malaria in the study population. However, there is need for continued monitoring of its effectiveness in children and adults to counter the threat of resistance.

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Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade after its use in Kenya

10.21203/rs.3.rs-22339/v2 ◽

2020 ◽

Author(s):

gabriel m kishoyian ◽

Eliud N.M. Njagi ◽

George O. Orinda ◽

Francis T. Kimani ◽

Kevin Thiongo ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Uncomplicated Malaria ◽

Standard Dose ◽

Parasite Clearance ◽

Close Monitoring ◽

First Line ◽

Study Population ◽

Lost To Follow Up ◽

Line Drug

Abstract Background: Plasmodium falciparum resistance to antimalarial drugs remains to be a major threat to the control of the disease globally. After the deployment of artemisinin-based combination therapy (ACT), there have been reports of reduced sensitivity of the drug to parasite clearance. In Kenya, artemisinin-lumefantrine (AL) is the recommended first-line drug in the treatment of uncomplicated malaria. This study sought to assess the efficacy of AL after its reintroduction in Kenya, a decade later. We assessed clinical and parasitological responses of children under five years in May and November 2015 in Chulaimbo sub-County, Kisumu, Kenya. Method: Patients of ≥6 and ≤60 months of age with confirmed Plasmodium falciparum mono-infection were enrolled in the study. The children were inpatient for close monitoring, they were treated with a standard dose of AL under supervision of a qualified nurse and followed up for 28 days. We monitored treatment adherence and responses. Efficacy of artemether lumefantrine on Plasmodium falciparum was determined.Results: Of the 90 patients enrolled, fourteen (14) were lost to follow-up, with 76 completing the study period. Seventy-five patients 75 (98.7%) cleared the parasitemia within 48 hours while one (1.3%) cleared on day 3. There was 100% clinical and parasitological parasite clearance. Conclusion: Artemisinin lumefantrine was found to be highly efficacious to plasmodium falciparum parasites in children aged ≥6 and ≤60 months. The results reported here indicate that the drug can be used to treat uncomplicated malaria in the study population. However, there is need for continued monitoring of its effectiveness in children and adults to counter the threat of resistance.

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Persistence of High In Vivo Efficacy and Safety of Artesunate–Amodiaquine and Artemether–Lumefantrine as the First- and Second-Line Treatments for Uncomplicated Plasmodium falciparum Malaria 10 Years After Their Implementation in Gabon

Acta Parasitologica ◽

10.2478/s11686-019-00115-y ◽

2019 ◽

Vol 64 (4) ◽

pp. 898-902

Author(s):

Jacques M. Ndong Ngomo ◽

Guy J. Ondzagha Megnie ◽

Bridy Moutombi Ditombi ◽

Jeanne V. Koumba Lengongo ◽

Noé P. M’Bondoukwé ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Adverse Events ◽

Uncomplicated Malaria ◽

Plasmodium Falciparum Malaria ◽

Parasite Resistance ◽

Serious Adverse Events ◽

Uncomplicated Plasmodium Falciparum Malaria ◽

Who 2008

Abstract Purpose Artesunate–amodiaquine (AS–AQ) and artemether–lumefantrine (AL) have been widely used for the treatment of uncomplicated Plasmodium falciparum malaria since 2005 in Gabon. Since 2011, a rebound of malaria morbidity has been observed in this country, while no survey evaluating ACT efficacy was performed. During the same period, parasite resistance against artemisinin has been reported in Asia. The aim of this study was to assess the efficacy and tolerability of these two drugs in two sentinel sites of Gabon 10 years after their implementation. Methods Children aged from 12 to 144 months with uncomplicated malaria were recruited at the Regional Hospital of Melen, Libreville and in the Urban Health Center of Franceville between March 2014 and September 2015. The therapeutic efficacy was evaluated according to the WHO 2008 protocol of 28-day follow-up and PCR-uncorrected/corrected treatment outcomes were assessed. Results One hundred and eighty-five children (98 ASAQ and 89 AL) were followed up until day 28. The PCR-corrected ACPR was 98.9% for AS–AQ and 96.4% for AL. Late therapeutic failure rate was 3.6% and 1.1% for AL and AS–AQ, respectively (p = 0.2). Adverse events and serious adverse events were rarely observed with both treatments. Conclusion AS–AQ and AL are still efficacious and well-tolerated for the treatment of uncomplicated malaria in Gabonese children.

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Dihydroartemisinin-piperaquine for the routine treatment of uncomplicated malaria in Northern Ghana

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20200200 ◽

2020 ◽

Vol 7 (1) ◽

pp. 1

Author(s):

Abraham R. Oduro ◽

Samuel Chatio ◽

Emmanuel Ayamba ◽

Thomas Anyorigiya ◽

Fred Binka ◽

...

Keyword(s):

Uncomplicated Malaria ◽

Haemoglobin Concentration ◽

Febrile Illness ◽

Northern Ghana ◽

First Line ◽

Intention To Treat ◽

Health Delivery ◽

Baseline Temperature ◽

Concentration Changes

Background: Dihydroartemisinin-piperaquine is a first line treatment for uncomplicated malaria in Ghana. A facility-based study was undertaken to examine the effectiveness of the treatment in the routine health care system.Methods: The study was undertaken at the Navrongo demographic surveillance area. Patients presenting with acute febrile illness were enrolled after informed consented and confirmation by microscopy. Patients were randomized into supervised group who received treatment under direct observation and unsupervised group which had only the first treatment given under supervision. Treatment was according to bodyweight and 42 days follow-up was undertaken.Results: A total of 194 patients were enrolled; 54.1% were females and 51% had supervised treatment. The median age and weight were 6.7 years and 20.0 kg respectively. Mean baseline temperature, haemoglobin concentration and parasite density were, 37.6 oC, 11.1 g/dl and 11,098 parasites per microliter of blood respectively. Study completion rate was 93.3%, day 42 polymerase chain reaction-unadjusted adequate clinical and parasitological responses rate (ACPR) was 93.4% by evaluable and 87.1 % by intention-to-treat (ITT). The day 42 ACPR by evaluable was 92.3% in the supervised arm compared to 94.4% in the unsupervised arm. The day 42 ACPR by ITT was 85.7% in the supervised and 88.5% in the unsupervised arms. The fever resolution and haemoglobin concentration changes for the two arms were similar.Conclusions: The results show that dihydroartemisinin-piperaquine is effective and good first-line antimalarial in the routine health delivery system.

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Promising Immunotherapy in Metastatic Testicular Sex Cord Stromal Tumours After First-Line Chemotherapy

Frontiers in Immunology ◽

10.3389/fimmu.2021.720359 ◽

2022 ◽

Vol 12 ◽

Author(s):

Bingqing Shang ◽

Chuanzhen Cao ◽

Weixing Jiang ◽

Hongzhe Shi ◽

Xingang Bi ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Chemotherapy Resistance ◽

Progression Free Survival ◽

Retroperitoneal Lymph Node Dissection ◽

First Line ◽

Experienced Grade ◽

Line Chemotherapy

BackgroundTesticular sex cord stromal tumours (TSCSTs) are rare, with few studies focusing on the metastatic TSCST prognosis. The value of treatments, including radical orchiectomy (RO) and retroperitoneal lymph node dissection (RPLND), in preventing metastasis is controversial. Additionally, metastatic TSCSTs are resistant to chemotherapy. We aimed to assess the effectiveness and safety of immunotherapy in metastatic TSCSTs after first-line chemotherapy.MethodsWe retrospectively screened patients with testicular tumours undergoing testis surgery between January 2005 and January 2019. Patients with TSCSTs who had undergone testis-sparing surgery (TSS) or RO were identified. The malignant type was defined as metastasis confirmed by pathology. Treatment responses, progression-free survival (PFS), overall survival (OS) and safety were analysed.ResultsAmong the 494 testicular tumour patients who received TSS or RO, 11 (2.2%) patients with histologically proven TSCSTs were identified. At the last follow-up, 7 patients survived without tumours, and 4 patients developed metastasis and received first-line cisplatin-based chemotherapy, with 1 of them achieving an objective response. Their PFS times were 1.5, 2.2, 9.0, and 17.0 months, respectively. Two patients received immune checkpoint inhibitors (ICIs) after developing chemotherapy resistance and achieved a partial response up to the last follow-up; one of them experienced Grade 1 adverse events, and the other experienced Grade 2 adverse events during immunotherapy. The median OS time of the 4 patients with metastatic TSCSTs was 32 months.ConclusionsTSCSTs are rare, and most are benign with a good prognosis. ICIs represent a promising option for improving clinical outcomes in metastatic TSCSTs.

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First-line treatment with Bendamustine plus Rituximab for patients with indolent non-Hodgkin’s lymphoma or Mantle cell lymphoma: Real-world experience.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e19540 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e19540-e19540

Author(s):

Rouslan Kotchetkov ◽

David Susman ◽

Lauren Gerard ◽

Erica DiMaria ◽

Derek Wayne Nay

Keyword(s):

Adverse Events ◽

Hodgkin’S Lymphoma ◽

Cell Lymphoma ◽

Hodgkin's Lymphoma ◽

First Line ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Mantle Cell ◽

Grade 3

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m2. A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.

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High-Dose Chloroquine for Uncomplicated Plasmodium falciparum Malaria Is Well Tolerated and Causes Similar QT Interval Prolongation as Standard-Dose Chloroquine in Children

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01846-19 ◽

2020 ◽

Vol 64 (3) ◽

Cited By ~ 9

Author(s):

Johan Ursing ◽

Lars Rombo ◽

Staffan Eksborg ◽

Lena Larson ◽

Anita Bruvoll ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Adverse Events ◽

Standard Dose ◽

Plasmodium Falciparum Malaria ◽

Parasite Clearance ◽

Chloroquine Resistance ◽

High Dose ◽

Qtc Interval ◽

Content Type ◽

Qt Interval Prolongation

ABSTRACT Higher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for 2 days and 5 mg/kg twice daily on the third day. Fifteen additional children were given 5 mg/kg twice daily for 2 more days. Chloroquine concentrations, blood pressure, electrocardiograms (ECGs), parasite density, and adverse events were assessed until day 28. Both dosages were well tolerated, and symptoms resolved by day 3 in parallel with increasing chloroquine concentrations. The median corrected QT (QTc) interval was 12 to 26 ms higher at expected peak concentrations than at day 0 (P < 0.001). Pfcrt 76T was associated with delayed parasite clearance. Day 28 clinical and parasitological responses against P. falciparum with pfcrt 76T were 57% (4/7) and 67% (4/6) after treatment with 50 and 70 mg/kg, respectively. Dosages were well tolerated, and no severe cardiac adverse events occurred. The QTc interval increase was similar to that found in adults taking 25 mg/kg of chloroquine. (This study has been registered at ClinicalTrials.gov under identifier NCT01814423.)

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Cost-Effectiveness of Imatinib Versus Interferon-α in the Treatment of Patients Newly Diagnosed with Chronic Myeloid Leukemia, under the Brazilian Public Healthcare System Perspective.

Blood ◽

10.1182/blood.v108.11.3314.3314 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3314-3314 ◽

Cited By ~ 2

Author(s):

Fábio Mataveli ◽

Alessandra Calabró ◽

Wellington Mendes ◽

Denizar Vianna ◽

Pedro Dorlhiac-Llacer ◽

...

Keyword(s):

Cost Effectiveness ◽

Chronic Myeloid Leukemia ◽

Adverse Events ◽

Myeloid Leukemia ◽

Public Healthcare ◽

Line Treatment ◽

Newly Diagnosed ◽

First Line ◽

System Perspective

Abstract The 60-month follow-up data for patients randomized to imatinib in IRIS demonstrated significant clinical improvements in survival rates and QALYs gained (17,09 years;13,58 QALYs) in patients newly diagnosed with chronic myeloid leukemia (CML) and treated with imatinib in comparison to patients under interferon-alpha (INF-α) (9,10 years;6,31 QALYS) as first line therapy. Although reimbursed as second line therapy for chronic phase CML patients who did not respond to INF-α, imatinib was not considered for public reimbursement as first line treatment in Brazil based solely on drug costs. An economic evaluation of imatinib as first line treatment versus INF-α was performed under the Brazilian Public Heathcare System perspective, according to the long-term follow-up data from IRIS, literature recommendations and prior health technology assessment from the National Institute for Clinical Excellence (NICE) to consider long term follow-up survival and adverse events costs. This study was aimed to evaluate the cost-effectiveness of imatinib compared with IFN-α for first-line treatment of chronic myeloid leukemia under the Brazilian public healthcare system perspective. For the economic model, a base case of 100 patients for each treatment option was constructed focused on drug costs and adverse events. Drug costs were estimated based on the Brazilian public healthcare reimbursement payment (APAC-SUS) for chronic phase CML treatment. Febrile neutropenia (grade III and IV), depression, nausea and abnormal liver-function results were considered as adverse events. Clinical guidelines and protocols from two public hematology Brazilian centers, Fundação Pró-Sangue FM-USP and Instituto Nacional do Cancer, were used to estimate adverse events treatment costs. Adverse events frequency for all grades was based on data published by NICE and the Agency for Health Care Research and Quality. Due to the high crossover rate from INF-α to Imatinib group observed in the IRIS study (90% from INF-α to imatinib within a year of study entry) the estimated life time survival for INF-α treatment group was based on the European Study Group on Interferon in Chronic Myeloid Leukemia. Utilities values from the IRIS study were used for both groups. Annual discount rates were of 6% for costs and 1.5% for QALYs. The annual average costs for the treatment of adverse effects in the INF-α were 1.83 higher than the imatinib group. Adverse events lifetime costs for INF-α were 24% higher than imatinib, even tough imatinib granted a projected 6.3 years survival advantage over INF-α. The resulting incremental cost-effectiveness ratio (ICER) of imatinib, compared with IFNα, considering adverse events was US$ 18,637 per QALY gained. Assuming a conservative cost-effectiveness threshold of less than US$ 25,500, which is three times the GDP per capita in Brazil (US$ 8,500 in 2005), the ICER for imatinib compared with INF-α falls within the range considered by the World Heath Organization as a cost-effective fist line treatment for patients newly diagnosed with CML.

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Imatinib Long Term Effects (ILTE) Study: An Independent, International Study in CML Patients.

Blood ◽

10.1182/blood.v112.11.1099.1099 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1099-1099

Author(s):

Carlo Gambacorti-Passerini ◽

Dong-Wook Kim ◽

François-Xavier Mahon ◽

Giuseppe Saglio ◽

Fabrizio Pane ◽

...

Keyword(s):

Adverse Events ◽

International Study ◽

Imatinib Treatment ◽

Long Term Effects ◽

First Line ◽

Eligibility Criteria ◽

Serious Adverse Events ◽

Second Cancers

Abstract Imatinib is an effective first line therapy for chronic myeloid leukemia (CML) and has substantially changed its biological and clinical behavior. Durable complete cytogenetic responses (CCyR) were reported in the majority of patients, with a rather benign side effect profile, despite the ‘off target’ inhibition of several other kinases, including Kit, PDGFR and Lck. Since available information is largely based on industry-sponsored trials and long-term field studies are lacking, the ILTE study was conceived as an industryindependent, academic, multicenter trial supported by the Italian Drug Safety Agency (AIFA). ILTE is an international study on a retrospective cohort and includes 31 centers in Europe, North/South America, Africa and Asia; therefore it is uniquely positioned to present a global picture of imatinib long-term effects. Consecutive patients with Ph+ CML who started imatinib between 01 September 1999 and 31 December 2004 were eligible if they were in Complete Cytogenetic Response (CCyR) after two years of imatinib treatment. Study endpoints were survival, serious adverse events (SAE, including second cancers), toxicities not qualifying as SAE (NSAE) but judged by the referring physician as substantially impacting quality of life, loss of CCyR, and development of PCR negativity. A total of 957 patients were enrolled, 92% of which met eligibility criteria. The median age of eligible patients was 50 (range 15–92) years; 59% of patients were males and the median follow-up was 3.1 years (excluding the first 2 years of treatment). As of Dec. 31 2007, 2564 person years were available for analysis. Eleven deaths were observed (only 3 of them caused by relapsed CML), with a standardized rate of 0.4/100 person years and an observed/expected ratio of 0.48 (95% CI = 0.24–0.85). One-hundred SAE were recorded (rate 3.9/100 person years, most frequent type “heart failure”), with 21% being considered related to imatinib. Second cancers were documented in 28 patients (rate 1.1/100 person years), with an observed/expected ratio of 1.27 (95% CI = 0.84–1.84). Among the 576 NSAE recorded (0.65/patient) the most frequent types were “edema, cramps, skin fragility, diarrhea”; 71% of them were related to imatinib. A total of 12 patients (1.4 %) discontinued imatinib because of toxicities during the period of observation. Thirty-four patients lost CCyR, corresponding to a rate of 1.4/100 person years (1.0 in patients with imatinib as first-line treatment, 1.5 in patients who were treated with imatinib >6 months after diagnosis), with stable or increasing rates over time. Finally, 214 patients (24.5%) developed durable (> 1 year) PCR negativity. In conclusion, the first report from ILTE shows that CML patients on imatinib die unfrequently of CML related causes, do not appear to have substantially higher second cancer rates than the general population, have mortality rates lower than expected in an age/sex matched population and do not show new types of imatinib-related adverse events. They also experience a low but steady rate of loss of CCyR and develop PCR negativity in approximately ¼ of cases. Follow-up and further analysis are ongoing. (Presented on behalf of the ILTE Investigators group)

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Comparison of the frequency of adverse events requiring interventions determined by telephone follow up in hepatocellular carcinoma patients treated with sorafenib and lenvatinib.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.507 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 507-507

Author(s):

Koki Morishita ◽

Hidetaka Suzuki ◽

Junko Tauchi ◽

Misaki K Takeno ◽

Kohei Hayashi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Treatment Withdrawal ◽

Cancer Center ◽

First Line ◽

Sorafenib Treatment ◽

Number Of Patients ◽

Center Hospital ◽

Hand Foot Syndrome

507 Background: The REFLECT trial demonstrated that lenvatinib is non-inferior to sorafenib for first-line treatment of unresectable hepatocellular carcinoma (uHCC). However, no comparison of the frequency of adverse events (AEs) requiring interventions has been reported yet between uHCC patients receiving sorafenib and those receiving lenvatinib. At the National Cancer Center Hospital East, Japan, pharmacists conduct telephone follow-up (TF) during the first month after the start of treatment with sorafenib or lenvatinib in uHCC patients, for the purpose of detecting and treating AEs early. The aim of this study was to reveal the frequency of AEs requiring interventions between patients receiving sorafenib and those receiving lenvatinib, based on TF. Methods: The characteristics, AEs and contents of intervention by TF of 56 uHCC patients who had been started on treatment with sorafenib and lenvatinib were reviewed retrospectively. The study subjects were 33 patients initiated on sorafenib treatment and monitored by TF from March 2017 to March 2018 (Group S) and 23 patients initiated on lenvatinib treatment and monitored by TF from March 2018 to March 2019 (Group L). Results: The total numbers of TFs in Group S and Group L were 91 and 48, respectively. The rate of AEs requiring interventions was significantly higher in Group S as compared to Group L (Group S, 17.6% (16/91); Group L, 4.2% (2/48); p = 0.032). The frequencies of the interventions, including use of supportive treatments (A), withdrawal of sorafenib or lenvatinib (B), and medical examination (C), differed between the two groups (A/B/C: Group S, 8/5/3 times vs. Group L, 2/0/0 times). The most frequently observed AE that necessitated intervention in Group S was the hand-foot syndrome (HFS) (75.0%, 12/16). Conclusions: The frequency of interventions for AEs appears to be higher in uHCC patients receiving sorafenib than in those receiving lenvatinib. Although a great number of patients taking sorafenib had symptomatic AEs, such as HFS, early detection of the symptoms through TF contributed to prevention of treatment withdrawal on account of AEs.

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