Evidence map›Paper›PMID 25461806›Full record

ArticleBritish journal of cancer2015

Combination of letrozole, metronomic cyclophosphamide and sorafenib is well-tolerated and shows activity in patients with primary breast cancer.

L Bazzola, C Foroni, D Andreis, V Zanoni, M R Cappelletti, G Allevi, S Aguggini, C Strina, M Milani, S Venturini and 13 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 23% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
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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

23 authors at 6 institutions in 3 countries.

L BazzolaU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
C ForoniU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
D AndreisU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
V ZanoniU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
M R CappellettiU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
G AlleviU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
S AgugginiU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
C StrinaU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
M MilaniU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
S VenturiniU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
F FerrozziU.O. Diagnostica per Immagini-Figlie di San Camillo-Via F Filzi 56, Cremona, Italy.
R GiardiniU.O. di Anatomia Patologica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
R BertoniU.O. di Anatomia Patologica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
H TurleyCRUK Tumor Pathology Group, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DS, UK.
K GatterCRUK Tumor Pathology Group, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DS, UK.
P G PetroniniDipartimento di Medicina Sperimentale, Via Volturno, 39, 43100 Parma, Italy.
S B FoxPeter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia.
A L HarrisWeatherall Molecular Oncology Laboratories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
M MartinottiU.O. Chirurgia Generale, Dipartimento di Chirurgia, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
A BerrutiU.O. Chirurgia Generale, Dipartimento di Chirurgia, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
A BottiniU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
A R ReynoldsBreakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London SW3 6JB, UK.
D GeneraliU.O.di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
Istituti Ospitalieri di Cremona · ITUniversity of Oxford · GBInstitute of Cancer Research · GBJohn Radcliffe Hospital · GBOspedale di Parma · ITPeter MacCallum Cancer Centre · AU

Funding

Cancer Research UK 11359Cancer Research UK 18974
6 · The paper itself

Abstract

purposeTo assess whether the combination of letrozole, metronomic cyclophosphamide and sorafenib (LCS) is well tolerated and shows activity in primary breast cancer (BC).

methodsThirteen oestrogen receptor-positive, postmenopausal, T2-4, N0-1 BC patients received the LCS combination for 6 months. In these patients we examined the pharmacokinetics of sorafenib and cyclophosphamide, toxicity of the regimen, the clinical response to therapy and changes in the levels of biologically relevant biomarkers.

resultsAdequate plasma concentrations of sorafenib were achieved in patients when it was dosed in combination with L+C. The mean plasma concentrations of C were consistently lower following administration of LCS, compared with administration of L+C only. The most common drug-related grade 3/4 adverse events were skin rash (69.3%), hand-foot skin reaction (69.3%) and diarrhoea (46.1%). According to RECIST Criteria, a clinical complete response was observed in 6 of 13 patients. A significant reduction in tumour size, evaluated with MRI, was also observed between baseline and 14 days of treatment in all 13 patients (P=0.005). A significant reduction in SUV uptake, measured by (18)FDG-PET/CT, was observed in all patients between baseline and 30 days of treatment (P=0.015) and between baseline and definitive surgery (P=0.0002). Using modified CT Criteria, a response was demonstrated in 8 out of 10 evaluable patients at 30 days and in 11 out of 13 evaluable patients at the definitive surgery. A significant reduction in Ki67 expression was observed in all patients at day 14 compared with baseline (P<0.00001) and in 9 out of 13 patients at the definitive surgery compared with baseline (P<0.03). There was also a significant suppression of CD31 and VEGF-A expression in response to treatment (P=0.01 and P=0.007, respectively).

conclusionsThe LCS combination is feasible and tolerable. The tumour response and target biomarker modulation indicate that the combination is clinically and biologically active.

Indexed as

Administration, MetronomicAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCyclophosphamideFemaleHumansLetrozoleMiddle AgedNiacinamideNitrilesPhenylurea CompoundsRandomized Controlled Trials as TopicSorafenibAntineoplastic AgentsBiomarkers, TumorCyclophosphamideLetrozoleNiacinamideNitrilesPhenylurea CompoundsSorafenibTriazoles

Identifiers

PMID25461806
PMCPMC4453610
OpenAlexW1975222023

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LicenceCC BY-NC-SA
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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.