| Title |
Phase I dose-escalation study of milciclib in combination with gemcitabine in patients with refractory solid tumors
|
|---|---|
| Published in |
Cancer Chemotherapy and Pharmacology, April 2017
|
| DOI | 10.1007/s00280-017-3303-z |
| Pubmed ID | |
| Authors |
Sandrine Aspeslagh, Kunwar Shailubhai, Rastilav Bahleda, Anas Gazzah, Andréa Varga, Antoine Hollebecque, Christophe Massard, Anna Spreafico, Michele Reni, Jean-Charles Soria |
| Abstract |
This phase I trial evaluated the safety and tolerability of milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin receptor kinase A, in combination with gemcitabine in patients with refractory solid tumors. Sixteen patients were enrolled and treated with milciclib at three dose levels (45 mg/m(2)/day, n = 3; 60 mg/m(2)/day, n = 3; and 80 mg/m(2)/day, n = 10) with a fixed dose of gemcitabine (1000 mg/m(2)/day). Milciclib was administered orally once daily for 7 days on/7 days off in a 4-week cycle, and gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle. All 16 enrolled patients were evaluable for safety and toxicity. Dose-limiting toxicities, which occurred in only one out of nine patients treated at the maximum dose tested (milciclib 80 mg/m(2)/day and gemcitabine 1000 mg/m(2)/day), consisted of Grade 4 thrombocytopenia, Grade 3 ataxia and Grade 2 tremors in the same patient. Most frequent treatment-related AEs were neutropenia and thrombocytopenia. Among 14 evaluable patients, one NSCLC patient showed partial response and 4 patients (one each with thyroid, prostatic, pancreatic carcinoma and peritoneal mesothelioma) showed long-term disease stabilization (>6-14 months). Pharmacokinetics of the orally administered milciclib (~t1/2 33 h) was not altered by concomitant treatment with gemcitabine. The combination treatment was well tolerated with manageable toxicities. The recommended phase II dose was 80 mg/m(2)/day for milciclib and 1000 mg/m(2)/day for gemcitabine. This combination treatment regimen showed encouraging clinical benefit in ~36% patients, including gemcitabine refractory patients. These results support further development of combination therapies with milciclib in advanced cancer patients. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 34 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 6 | 18% |
| Student > Ph. D. Student | 4 | 12% |
| Student > Doctoral Student | 4 | 12% |
| Researcher | 3 | 9% |
| Professor > Associate Professor | 3 | 9% |
| Other | 7 | 21% |
| Unknown | 7 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 26% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 12% |
| Biochemistry, Genetics and Molecular Biology | 4 | 12% |
| Nursing and Health Professions | 2 | 6% |
| Chemistry | 2 | 6% |
| Other | 5 | 15% |
| Unknown | 8 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 80. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 February 2023.
All research outputs
#527,039
of 25,381,864 outputs
Outputs from Cancer Chemotherapy and Pharmacology
#9
of 2,565 outputs
Outputs of similar age
#10,824
of 315,883 outputs
Outputs of similar age from Cancer Chemotherapy and Pharmacology
#2
of 42 outputs
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So far Altmetric has tracked 2,565 research outputs from this source. They receive a mean Attention Score of 4.5. This one has done particularly well, scoring higher than 99% of its peers.
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