scholarly journals Artemisinin Combination Therapy Can Result in Clinical Failure If Oral Therapy Is Not Directly Observed

2013 ◽  
Vol 24 (4) ◽  
pp. 215-216
Author(s):  
Wilson W Chan ◽  
Divya Virmani ◽  
Dylan R Pillai
Keyword(s):  
Combination Therapy ◽  
Treatment Failure ◽  
Oral Therapy ◽  
Present Report ◽  
Artemisinin Combination Therapy ◽  
Clinical Failure ◽  
First Line ◽  
Early Administration ◽  
First Line Therapy ◽  
Line Therapy

Intravenous artesunate therapy is the first-line therapy for severe malaria, and is highly efficacious when used in combination with an oral partner drug such as doxycycline or atovaquone-proguanil. However, treatment failure occurs routinely with artesunate monotherapy due to the very short half-life of this drug. In North America, experience with artesunate is limited. With the pressure to discharge patients early, administration of the essential oral partner drug is often left to the discretion of the patient. Thus, treatment failure may be commonplace if nonadherence is a factor, as was observed in the case described in the present report.

scholarly journals Multifactorial Role of Mitochondria in Echinocandin Tolerance Revealed by Transcriptome Analysis of Drug-Tolerant Cells

mBio ◽  
2021 ◽  
Author(s):  
Rocio Garcia-Rubio ◽  
Cristina Jimenez-Ortigosa ◽  
Lucius DeGregorio ◽  
Christopher Quinteros ◽  
Erika Shor ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Clinical Failure ◽  
First Line ◽  
Content Type ◽  
First Line Therapy ◽  
Line Therapy ◽  
Resistant Strains ◽  
Opportunistic Fungal Pathogen

Echinocandin drugs are a first-line therapy to treat invasive candidiasis, which is a major source of morbidity and mortality worldwide. The opportunistic fungal pathogen Candida glabrata is a prominent bloodstream fungal pathogen, and it is notable for rapidly developing echinocandin-resistant strains associated with clinical failure.

Clinical study of nab-paclitaxel in combination with S-1 as first-line therapy in patients with advanced pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15765-e15765 ◽  
Author(s):  
Yi Hu ◽  
Danyang Sun
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Medical Center ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Standard Regimen ◽  
First Line Therapy ◽  
Line Therapy

e15765 Background: Pancreatic cancer is one of the highest cancer-mortality diseases worldwide with limited treatment. Most patients had local advanced or metastatic disease at the time of diagnosis. Gemcitabine-based therapy has been standard regimen in the past few decades. It is necessary to find new strategies of treatment. Methods: The aim of this study was to evaluate the efficacy and safety of nab-paclitaxel in combination with S-1 as first-line therapy in advanced pancreatic cancer. We retrospectively evaluated 79 patients with advanced pancreatic cancer from 2014 to 2016 treated in our medical center. All the patients received at least two cycles of combination therapy. Nab-paclitaxel was administered 260mg/ m2 as a total dose on day 1 and 5 or on day 1 and 8. S-1 was administered orally twice a day for 14 days according to body surface area. S-1 monotherapy was administered as maintenance treatment after 6 to 8 cycles of combination therapy until the progression of disease. Results: In all the 79 patients enrolled, the median age was 56, range from 36 to 77, 56 (70.9%) patients had KPS 90, 58 (73.4%) patients had multiple metastatic sites. The overall response rate was 51.9%; median progression-free survival was 5.7 months (95%CI 5.010-6.292); median overall survival was 11.9 months (95%CI 9.731-13.990). The efficacy of CA19-9 decrease > 50% was significant higher compared with those of CA19-9 decrease < 50%. Treatment was well tolerated. Grade 4 toxicity was only reported in neutropenia of 5 patients. Grade 3 adverse events include neutropenia in patients (13.9%), nausea and vomiting in one patient (1.3%), peripheral sensory in one patient (1.3%) and alopecia in 3 patients (3.8%). Conclusions: Nab-paclitaxel in combination with S-1 as first-line therapy demonstrated promising antitumor activity and well-tolerated toxicities and presents a new alternative for locally advanced and metastatic pancreatic cancer.

scholarly journals Current Perspectives on Taxanes: Focus on Their Bioactivity, Delivery and Combination Therapy

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 569
Author(s):  
Jan Škubník ◽  
Vladimíra Pavlíčková ◽  
Tomáš Ruml ◽  
Silvie Rimpelová
Keyword(s):  
Combination Therapy ◽  
Targeted Drug Delivery ◽  
Water Solubility ◽  
Review Article ◽  
Ovarian Hormone ◽  
First Line ◽  
Stabilizing Agents ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hormone Refractory

Taxanes, mainly paclitaxel and docetaxel, the microtubule stabilizers, have been well known for being the first-line therapy for breast cancer for more than the last thirty years. Moreover, they have been also used for the treatment of ovarian, hormone-refractory prostate, head and neck, and non-small cell lung carcinomas. Even though paclitaxel and docetaxel significantly enhance the overall survival rate of cancer patients, there are some limitations of their use, such as very poor water solubility and the occurrence of severe side effects. However, this is what pushes the research on these microtubule-stabilizing agents further and yields novel taxane derivatives with significantly improved properties. Therefore, this review article brings recent advances reported in taxane research mainly in the last two years. We focused especially on recent methods of taxane isolation, their mechanism of action, development of their novel derivatives, formulations, and improved tumor-targeted drug delivery. Since cancer cell chemoresistance can be an unsurpassable hurdle in taxane administration, a significant part of this review article has been also devoted to combination therapy of taxanes in cancer treatment. Last but not least, we summarize ongoing clinical trials on these compounds and bring a perspective of advancements in this field.

scholarly journals Efficacy and Tolerability of the Bevacizumab/carboplatin/paclitaxel Combination Therapy as First-line or Non-first-line Therapy for Non-small-cell Lung Cancer

Haigan ◽  
2012 ◽  
Vol 52 (7) ◽  
pp. 1007-1016 ◽  
Author(s):  
Makoto Nakashima ◽  
Ryoko Ohnishi ◽  
Mizuho Kobayashi ◽  
Toshitaka Suzuki ◽  
Shigeo Yasuda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Combination Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Clinical and treatment patterns in neuromyelitis optica: a retrospective study from a single centre

2019 ◽  
Vol 6 (4) ◽  
pp. 1277
Author(s):  
Kamlesh A. Jagiasi ◽  
Shashank Nagendra ◽  
Afroz Ansari ◽  
Prachi Barvalia ◽  
Vikram Aglave
Keyword(s):  
Neuromyelitis Optica ◽  
Oral Therapy ◽  
Clinical Manifestations ◽  
Tertiary Hospital ◽  
Treatment Patterns ◽  
Published Data ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Oral Agents

Background: The aim of the study was to study the different presentations, treatment patterns and relapses on therapy in patients of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD).Methods: This is a retrospective, observational study in a tertiary hospital where Demographics, clinical manifestations at onset and at follow up and relapses, serum anti Aquaporin 4 antibody status, first line immunomodulatory therapy which was initiated and Relapses on first line therapy were noted.Results: Demographics and clinical presentation was largely similar to published data. 80% patients presented with LETM/ON at onset. Ten patients relapsed on oral therapy and trend was to shift from oral therapy to RTX after relapse on oral agent. No relapses were noted on RTX.Conclusions: Unaffordability and apprehension towards injections and cost were the factors affecting IMT decision, so majority received oral agents Aza/ MMF as first line therapy while remaining patients on oral therapy remained relapse free.

scholarly journals Imatinib dose optimisation following the disease progression in a patient with metastatic GIST

2015 ◽  
Vol 5 (4S) ◽  
pp. 3-6
Author(s):  
Mariangela Parodi ◽  
Monica Boitano ◽  
Luciano Canobbio
Keyword(s):  
Oral Therapy ◽  
Standard Dose ◽  
Evaluation Criteria ◽  
Response Evaluation ◽  
First Line ◽  
First Line Therapy ◽  
Metastatic Gist ◽  
Line Therapy ◽  
Dose Optimisation ◽  
Response Evaluation Criteria

Here we report a case of a man affected by metastatic GIST since march 2007. His oncologic history began in 2006 when he was submitted to ileal resection and diagnosis of abdominal GIST was made. He was free of disease at radiologic controls until march 2007, when peritoneal nodules were shown. He started imatinib as first line therapy at standard dose of 400 mg/day and he reached a partial response at 6 months according to Response Evaluation Criteria In Solid Tumors (RECIST). After 24 months he performed CT scan that showed progression disease. For this reason he increased imatinib dose to 800 mg/day. Imatinib was safely administered and radiologic analysis performed at 3 and 6 months demonstrated stable disease according to RECIST. The patient is continuing oral therapy with imatinib at 800 mg/day and the disease is still stable.

scholarly journals Spirit 2: Final 5 Year Analysis of the UK National Cancer Research Institute Randomized Study Comparing Imatinib with Dasatinib in Patients with Newly Diagnosed Chronic Phase CML

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 457-457 ◽  
Author(s):  
Stephen O'Brien ◽  
Leanne Cork ◽  
Valeria Bandeira ◽  
Ruth Bescoby ◽  
Letizia Foroni ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Board Of Directors ◽  
Research Funding ◽  
Molecular Response ◽  
Event Free Survival ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Objective. SPIRIT 2 is the largest phase 3 prospective randomized open-label trial comparing imatinib (I) 400mg with dasatinib (D) 100mg daily in newly diagnosed chronic phase CML. The primary endpoint was 5 year event-free survival. Methods. 812 (406 in each arm) of 814 patients recruited started study medication (median age 53.2, 275/812 (33.8%) were over 60 years old). Patients were recruited at 144 hospitals between August 2008 and March 2013 and randomized to receive either imatinib 400mg or dasatinib 100mg daily. Secondary endpoints included overall survival, rates of treatment failure, cytogenetic/molecular response - RT-PCR BCR-ABL/ABL ratio of <0.1%IS(major molecular response (MMR), 3 log reduction, MR3) and deeper. To address the potential confounding effect on the primary endpoint of patients switching from randomized treatment to an alternative TKI or other treatment, exploratory per-protocol analyses were performed using the inverse probability of censoring weighting (IPCW) method.Results. All patients have now completed 5 years of follow-up. 424/812 (52.2%) patients completed the study whilst still taking first line medication: 230/406 (56.7%) on dasatinib, 194/406 (47.8%) on imatinib. Of the patients who discontinued first line therapy, more patients on the imatinib arm switched due to suboptimal PCR response (as decided by the local investigator) than on dasatinib (D7/406, 1.7%; I71/406, 17.4%) but more patients on the dasatinib arm discontinued due to intolerance (D123/406, 30.3%; I68/406, 16.7%). More patients went on to transplant in the imatinib arm than in the dasatinib arm (D 6/406, 1.5%; I 30/406 7.6%) and in the imatinib patients undergoing transplant the reason for first line treatment failure was disease progression in 5/30 and suboptimal molecular response in 11/30. Using an intention to treat analysis cumulative incidence of MR3 and MR4 on first line therapy within 5 years was higher in the dasatinib arm than the imatinib arm (MR3: D 83.0%, I 63.0% - difference 20.0%, p<0.0001; MR4: D 77.5%, I 57.2% - difference 20.3%, p<0.0001).At 24 months the complete cytogenetic response rate was D 42.6%, I 31.8% - difference 10.8%, Chi-square test p=0.001.At 5 years the probability of treatment failure-free survival was higher with dasatinib than imatinib(D60.9%, I52.9% - HR: 0.73 (95%-CI:0.59-0.90), p=0.004) but there were no significant differences in event free survival (D91.0%, I89.0% - HR:0.80 (95%-CI:0.51-1.25), p=0.319) or overall survival (D91.9%, I91.2% - HR: 0.90 (95%-CI:0.56-1.47), p=0.690). IPCW modelling results will be presented at the meeting.The overall rate of pleural effusion over 5 years in the dasatinib arm was 36.0% with a higher incidence in older patients. 13 patients developed their first pleural effusion after 3 years on study. Conclusions. In SPIRIT 2 we observed a higher molecular and cytogenetic response rate and also a higher pleural effusion rate with dasatinib but a higher treatment failure rate with imatinib often because investigators were concerned about sub-optimal PCR responses. More imatinib-treated patients proceeded to transplant. There were no statistically significant differences in event free survival (the primary endpoint) or overall survival. Imatinib remains a highly effective first line therapy though subgroup analyses are planned to explore whether dasatinib may have advantages in particular clinical scenarios. Disclosures O'Brien: Bristol Myers Squibb: Research Funding; CTI: Other: Chair of Independent Data Monitoring Committee; National Institute for Health and Care Excellence (NICE): Other: Chair of Technology Appraisal Committee. Osborne:Servier: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; MSD: Honoraria; Roche: Honoraria; Novartis: Honoraria. Bell-Gorrod:Bristol-Myers Squibb: Consultancy; Merck EDM Serono: Consultancy; PharmaMar: Consultancy; Novartis: Consultancy; GlaxoSmithKline: Consultancy. Latimer:Pfizer: Consultancy; BMS: Consultancy; Merck: Consultancy; Astra Zeneca: Consultancy; Bluebirdbio: Consultancy; Janssen: Consultancy. Apperley:Incyte: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Byrne:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Pocock:Kent & Canterbury Hospital: Employment. Copland:Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Clark:Ariad/Incyte: Consultancy; Pfizer: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

Combination therapy for prostate cancer. Endocrine and biologic basis of its choice as new standard first-line therapy

Cancer ◽  
1993 ◽  
Vol 71 (S3) ◽  
pp. 1059-1067 ◽  
Author(s):  
Fernand Labrie ◽  
Alain Belanger ◽  
Jacques Simard ◽  
Claude Labrie ◽  
André Dupont
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Biologic Basis

Capecitabine Plus Erlotinib in Gemcitabine-Refractory Advanced Pancreatic Cancer

2007 ◽  
Vol 25 (30) ◽  
pp. 4787-4792 ◽  
Author(s):  
Matthew H. Kulke ◽  
Lawrence S. Blaszkowsky ◽  
David P. Ryan ◽  
Jeffrey W. Clark ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Failure ◽  
Advanced Pancreatic Cancer ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mutational Status ◽  
Gemcitabine Refractory ◽  
First Line Treatment

PurposeThe addition of either capecitabine or erlotinib to gemcitabine in the first-line treatment of advanced pancreatic cancer is associated with modest improvements in overall survival. We evaluated an oral regimen of capecitabine and erlotinib in patients with advanced pancreatic cancer who had experienced treatment failure with standard first-line therapy with gemcitabine.Patients and MethodsThirty patients with gemcitabine-refractory metastatic pancreatic cancer were treated with capecitabine, administered at a dose of 1,000 mg/m2twice daily for 2 weeks, followed by a 1-week break. All patients also received erlotinib 150 mg daily. Patients were observed for evidence of response, toxicity, and survival. EGFR mutational status was assessed in available tumor blocks.ResultsTreatment with capecitabine and erlotinib in gemcitabine-refractory patients was associated with an overall objective radiologic response rate of 10% and a median survival duration of 6.5 months. In addition, 17% of the treated patients experienced decreases in tumor marker (CA 19-9) levels of more than 50% from baseline. Common toxicities included diarrhea, skin rash, fatigue, and hand-foot syndrome. EGFR mutations were detected in two of five available tumors; no association between treatment response and EGFR mutational status was evident.ConclusionThe combination of capecitabine and erlotinib is active in patients with gemcitabine-refractory pancreatic cancer. This regimen may represent an acceptable treatment option in patients who experience treatment failure with standard first-line therapy with gemcitabine or for whom gemcitabine may not be an appropriate first-line treatment option.

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