| Title |
Phase I trial of afatinib plus vinorelbine in Japanese patients with advanced solid tumors, including breast cancer
|
|---|---|
| Published in |
Cancer Chemotherapy and Pharmacology, August 2015
|
| DOI | 10.1007/s00280-015-2826-4 |
| Pubmed ID | |
| Authors |
Hirofumi Mukai, Norikazu Masuda, Hiroshi Ishiguro, Ayako Mitsuma, Takashi Shibata, Jun Yamamura, Masakazu Toi, Aiko Watabe, Akiko Sarashina, Martina Uttenreuther-Fischer, Yuichi Ando |
| Abstract |
This phase I trial assessed afatinib, an irreversible ErbB family blocker, plus vinorelbine in Japanese patients with advanced solid tumors not amenable to standard treatment. Primary objectives were evaluation of safety and the maximum tolerated dose (MTD) of once-daily (QD) afatinib plus weekly intravenous vinorelbine. Secondary objectives included pharmacokinetic assessments and preliminary efficacy. Dose finding utilized a 3 + 3 design, with a starting dose of afatinib 20 mg QD plus vinorelbine 25 mg/m(2) weekly. Seventeen patients were enrolled. Dose level 2 (afatinib 40 mg and vinorelbine 25 mg/m(2)) exceeded the MTD; dose-limiting toxicities (DLTs) were considered vinorelbine-related. Dose finding continued with modified dose levels; dose level 2a: afatinib 40 mg and a reduced dose of vinorelbine 20 mg/m(2) and dose level 3: afatinib 40 mg and vinorelbine 25 mg/m(2) allowing omission of vinorelbine for grade ≥2 neutropenia/thrombocytopenia and afatinib dose modification for adverse events (AEs). At dose level 3, 1/6 patients had a DLT (upper abdominal pain requiring afatinib dose reduction). Overall, the most frequent treatment-related AEs (any/grade 3 and 4) were: neutropenia (100/71 %), leukopenia (100/59 %), diarrhea (94/0 %), anemia (71/12 %) and stomatitis (65/0 %). Two patients with breast cancer achieved a partial response; eight patients (various cancer indications) had stable disease. Pharmacokinetic analyses suggested no relevant drug-drug interactions. Afatinib 40 mg QD plus vinorelbine 25 mg/m(2) weekly was tolerated in Japanese patients when dose modifications for known AEs for either compound were allowed. Tumor shrinkage was also observed. This dose schedule was recommended for phase II/III trials in Japanese patients. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 2% |
| Unknown | 50 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 20% |
| Student > Master | 6 | 12% |
| Student > Ph. D. Student | 6 | 12% |
| Other | 5 | 10% |
| Student > Bachelor | 4 | 8% |
| Other | 7 | 14% |
| Unknown | 13 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 16 | 31% |
| Biochemistry, Genetics and Molecular Biology | 4 | 8% |
| Agricultural and Biological Sciences | 4 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
| Economics, Econometrics and Finance | 3 | 6% |
| Other | 5 | 10% |
| Unknown | 16 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 18 August 2015.
All research outputs
#19,221,261
of 23,815,455 outputs
Outputs from Cancer Chemotherapy and Pharmacology
#2,044
of 2,501 outputs
Outputs of similar age
#192,517
of 265,786 outputs
Outputs of similar age from Cancer Chemotherapy and Pharmacology
#12
of 25 outputs
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