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The search for a melanoma-tailored chemotherapy in the new era of personalized therapy: a phase II study of chemo-modulating temozolomide followed by fotemustine and a cooperative study of GOIM (Gruppo…

Overview of attention for article published in BMC Cancer, May 2018
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Title
The search for a melanoma-tailored chemotherapy in the new era of personalized therapy: a phase II study of chemo-modulating temozolomide followed by fotemustine and a cooperative study of GOIM (Gruppo Oncologico Italia Meridionale)
Published in
BMC Cancer, May 2018
DOI 10.1186/s12885-018-4479-2
Pubmed ID
Authors

Michele Guida, Stefania Tommasi, Sabino Strippoli, Maria Iole Natalicchio, Simona De Summa, Rosamaria Pinto, Antonio Cramarossa, Anna Albano, Salvatore Pisconti, Michele Aieta, Ruggiero Ridolfi, Amalia Azzariti, Gabriella Guida, Vito Lorusso, Giusepe Colucci

Abstract

It is frequently asked whether chemotherapy can still play a role in metastatic melanoma considering the effectiveness of the available drugs today, including antiCTLA4/antiPD1 immunotherapy and antiBRAF/antiMEK inhibitors. However, only approximately half of patients respond to these drugs, and the majority progress after 6-11 months. Therefore, a need for other therapeutic options is still very much apparent. We report the first large trial of a sequential full dose of fotemustine (FM) preceded by a low dose of temozolomide (TMZ) as a chemo-modulator in order to inactivate the DNA repair action of O(6)-methylguanine DNA-methyltransferase (MGMT). Primary endpoints were overall response and safety. We also evaluated specific biological parameters aiming to tailor these chemotherapies to selected patients. A total of 69 consecutive patients were enrolled. The main features included a median age of 60 years (21-81) and M1c stage, observed in 74% of the patients, with brain metastases in 15% and high LDH levels in 42% of the patients. The following schedule was used: oral TMZ 100 mg/m2 on days 1 and 2 and FM iv 100 mg/m2 on day 2, 4 h after TMZ; A translational study aiming to analyse MGMT methylation status and base-excision repair (BER) gene expression was performed in a subset of 14 patients. We reported an overall response rate of 30.3% with 3 complete responses and a disease control rate of 50.5%. The related toxicity rate was low and mainly of haematological types. Although our population had a very poor prognosis, we observed a PFS of 6 months and an OS of 10 months. A non-significant correlation with response was found with the mean expression level of the three genes involved in the BER pathway (APE1, XRCC1 and PARP1), whereas no association was found with MGMT methylation status. This schedule could represent a good alternative for patients who are not eligible for immune or targeted therapy or whose previous therapies have failed. EUDRACT 2009-016487-36l ; date of registration 23 June 2010.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 52 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 8 15%
Unspecified 6 12%
Other 6 12%
Researcher 5 10%
Student > Master 4 8%
Other 7 13%
Unknown 16 31%
Readers by discipline Count As %
Medicine and Dentistry 11 21%
Biochemistry, Genetics and Molecular Biology 8 15%
Unspecified 5 10%
Pharmacology, Toxicology and Pharmaceutical Science 4 8%
Nursing and Health Professions 2 4%
Other 5 10%
Unknown 17 33%

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 15 May 2018.
All research outputs
#18,610,562
of 23,053,169 outputs
Outputs from BMC Cancer
#5,468
of 8,372 outputs
Outputs of similar age
#252,630
of 326,006 outputs
Outputs of similar age from BMC Cancer
#135
of 205 outputs
Altmetric has tracked 23,053,169 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,372 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
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