Evidence map›Paper›PMID 30446785›Full record

ArticleCancer chemotherapy and pharmacology2019

A phase I study of single-agent BEZ235 special delivery system sachet in Japanese patients with advanced solid tumors.

Masanori Toyoda, Koichiro Watanabe, Taro Amagasaki, Kazuto Natsume, Hiromi Takeuchi, Cornelia Quadt, Kuniaki Shirao, Hironobu Minami

2 registry-linked trialsAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00620594 phase1completednot on this map

A Phase I/II, Multi-center, Open-label Study of BEZ235, Administered Orally on a Continuous Daily Dosing Schedule in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer

TypeinterventionalSponsorNovartis PharmaceuticalsRan2006 to 2013Enrolled183ConditionsBreast Cancer, Advanced Solid Tumors, Cowden SyndromeArmsBEZ235
NCT01195376 phase1completednot on this map

A Phase I Study of BEZ235, Administered Orally in Adult Japanese Patients With Advanced Solid Tumors

TypeinterventionalSponsorNovartis PharmaceuticalsRan2010 to 2013Enrolled35ConditionsAdvanced Solid TumorArmsBEZ235
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment.International journal of molecular sciences · 2024
    Review
  3. Article
  4. Review
  5. PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects.International journal of molecular sciences · 2021
    Review
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Masanori ToyodaDivision of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Koichiro WatanabeDepartment of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan.
Taro AmagasakiNovartis Pharma K.K, Tokyo, Japan.
Kazuto NatsumeNovartis Pharma K.K, Tokyo, Japan.
Hiromi TakeuchiNovartis Pharma K.K, Tokyo, Japan.
Cornelia QuadtNovartis Pharma AG, Basel, Switzerland.
Kuniaki ShiraoDepartment of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan.
Hironobu MinamiDivision of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. hminami@med.kobe-u.ac.jp.ORCID 0000-0001-8630-9145

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeBEZ235 is a dual kinase inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin, which are key components of the PI3K pathway. This was an open-label, multicenter, dose-escalation, phase I study of single-agent BEZ235 in Japanese oncology patients to determine the maximum tolerated dose (MTD) of BEZ235 based on dose-limiting toxicities (DLTs).

methodsDose escalation was guided by a standard 3 + 3 method and was based on DLTs observed in Cycle 1 and other safety, pharmacokinetic, and pharmacodynamic information. A total of 35 adult Japanese patients with advanced solid tumors received BEZ235 according to once daily (qd; n = 27) or twice daily (bid; n = 8) dosing schedules.

resultsTwo DLTs, namely, allergic reaction and thrombocytopenia, were observed at 1200 and 1400 mg qd, respectively, while liver dysfunction was reported as a DLT at 400 mg bid. The most common adverse events suspected to be related to BEZ235 in both dosing schedules were diarrhea, nausea, decreased appetite, stomatitis, and thrombocytopenia.

conclusionsAlthough the MTD was not established, the maximum clinically tolerable dose was determined to be 1200 mg because two out of six patients required dose reduction in Cycle 2. The recommended dose was determined to be 1000 mg qd, which was comparable with the results of the first-in-human BEZ235 study in Western patients with advanced solid tumors (NCT00620594). Additionally, the tolerability of BEZ235 400 mg bid in Japanese oncology patients was confirmed in this study. CLINICALTRIALS. GOV IDENTIFIER: NCT01195376.

Indexed as

Drug Delivery SystemsAdultAgedAntineoplastic AgentsFemaleFollow-Up StudiesHumansImidazolesJapanMaleMaximum Tolerated DoseMiddle AgedNeoplasmsPrognosisQuinolinesTissue DistributionAntineoplastic AgentsdactolisibImidazolesQuinolinesBEZ235InhibitormTORPhase IPI3K

Identifiers

PMID30446785
PMCPMC6394493

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.