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

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.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15765 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15765-e15765 ◽

Cited By ~ 1

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.

Download Full-text

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

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2013/427910 ◽

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.

Download Full-text

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 ◽

10.2482/haigan.52.1007 ◽

2012 ◽

Vol 52 (7) ◽

pp. 1007-1016 ◽

Cited By ~ 1

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

Download Full-text

Virus reactivations and serology patterns following first-line therapy with alemtuzumab or fludarabine-based combination therapy in patients with chronic lymphocytic leukemia

Blood Cancer Journal ◽

10.1038/bcj.2011.20 ◽

2011 ◽

Vol 1 (6) ◽

pp. e22-e22 ◽

Cited By ~ 1

Author(s):

C Karlsson ◽

H Dahl ◽

J Lundin ◽

E Rossmann ◽

M Brytting ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Combination Therapy ◽

Lymphocytic Leukemia ◽

First Line ◽

First Line Therapy ◽

Line Therapy

Download Full-text

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

Cancer ◽

10.1002/1097-0142(19930201)71:3+<1059::aid-cncr2820711426>3.0.co;2-6 ◽

1993 ◽

Vol 71 (S3) ◽

pp. 1059-1067 ◽

Cited By ~ 60

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

Download Full-text

Monotherapy versus combination therapy used as first-line therapy for primary hypertension

10.1002/14651858.cd010316 ◽

2013 ◽

Author(s):

Javier Garjón ◽

Ana Azparren ◽

José J Elizondo ◽

Idoia Gaminde ◽

Mª José Ariz ◽

...

Keyword(s):

Combination Therapy ◽

Primary Hypertension ◽

First Line ◽

First Line Therapy ◽

Line Therapy

Download Full-text

Outcomes after first-line therapy for immune/immune or immune/VEGF combinations.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.706 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 706-706

Author(s):

Francesca Jackson-Spence ◽

Agne Jovaisaite ◽

Michael Grant ◽

Wing-Kin Liu ◽

Thomas Butters ◽

...

Keyword(s):

Combination Therapy ◽

Immune Therapy ◽

Response Rates ◽

Second Line ◽

Front Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Group I

706 Background: The introduction of first line immune combination or immune/VEGF therapy in metastatic renal cancer has changed treatment landscape. Here we compare outcomes of these combinations with patients treated with first line sunitinib. The focus is on the impact of subsequent treatments. Methods: This retrospective analysis was performed at Barts Cancer Institute for consecutive patients from April 2015 when front line immune therapy was first used at our institution. Only patients enrolled on reported prospective trials were included to avoid selection bias. Patients were treated with VEGF targeted therapy (n=35) (group V), PD-1 + CTLA4 (n=15) (group I/I) or a combination of PD-L1 + VEGF TKI inhibitor (n=29) (group I/V). The primary analysis focused on the proportion of patients who received second line therapy and their outcome. Results: 79 patients received first line therapy for clear cell RCC. IMDC good, intermediate and poor risk occurred in 27.8%, 60.8% and 11.4% respectively. Front line response rates for V, I/I and I/V groups were 34.3%, 46.7% and 65.5% and PFS in V, I/I and I/V groups were 11mo (95%CI 6-16), 18mo (95% CI 0-41) and 36mo (95% CI 13-59), respectively (P= 0.016). OS in the 3 groups were immature but not significantly different. Second line therapy occurred in 87.5%, 92.9% and 81.8% in the V, I/I and I/V groups respectively (in those who progressed after initial therapy). Second line response rate post first line V, I/I and I/V were 11%, 0% and 0% respectively as per RECIST 1.1. 63% of patients receiving VEGF front line therapy subsequently received immune therapy. 95% of patients receiving first line immune/immune or immune/VEGF combination therapy received VEGF therapy in the second line. Only 70% of patients who progressed on second line therapy got 3rd line therapy across all arms. Conclusions: Response rates after front line immune combination therapy are modest. The sequencing of PD-1 therapy after VEGF monotherapy appears particularly relevant in outcomes. A high proportion of patients are sequencing therapy and reaching third line which may help improve outcomes.

Download Full-text