Evidence map›Paper›PMID 27166379›Full record

ArticleNeuro-oncology2016

Toca 511 plus 5-fluorocytosine in combination with lomustine shows chemotoxic and immunotherapeutic activity with no additive toxicity in rodent glioblastoma models.

Kader Yagiz, Tiffany T Huang, Fernando Lopez Espinoza, Daniel Mendoza, Carlos E Ibañez, Harry E Gruber, Douglas J Jolly, Joan M Robbins

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

Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Kader YagizTocagen Inc., San Diego, California (K.Y., T.T.H., F.L.E., D.M., C.E.I., H.E.G., D.J.J., J.M.R.) kyagiz@tocagen.com.
Tiffany T HuangTocagen Inc., San Diego, California (K.Y., T.T.H., F.L.E., D.M., C.E.I., H.E.G., D.J.J., J.M.R.).
Fernando Lopez EspinozaTocagen Inc., San Diego, California (K.Y., T.T.H., F.L.E., D.M., C.E.I., H.E.G., D.J.J., J.M.R.).
Daniel MendozaTocagen Inc., San Diego, California (K.Y., T.T.H., F.L.E., D.M., C.E.I., H.E.G., D.J.J., J.M.R.).
Carlos E IbañezTocagen Inc., San Diego, California (K.Y., T.T.H., F.L.E., D.M., C.E.I., H.E.G., D.J.J., J.M.R.).
Harry E GruberTocagen Inc., San Diego, California (K.Y., T.T.H., F.L.E., D.M., C.E.I., H.E.G., D.J.J., J.M.R.).
Douglas J JollyTocagen Inc., San Diego, California (K.Y., T.T.H., F.L.E., D.M., C.E.I., H.E.G., D.J.J., J.M.R.).
Joan M RobbinsTocagen Inc., San Diego, California (K.Y., T.T.H., F.L.E., D.M., C.E.I., H.E.G., D.J.J., J.M.R.).
E.ON (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundToca 511, a gamma retroviral replicating vector encoding cytosine deaminase, used in combination with 5-fluorocytosine (5-FC) kills tumor by local production of 5-fluorouracil (5-FU), inducing local and systemic immunotherapeutic response resulting in long-term survival after cessation of 5-FC. Toca 511 and Toca FC (oral extended-release 5-FC) are under investigation in patients with recurrent high-grade glioma. Lomustine is a treatment option for patients with high-grade glioma.

methodsWe investigated the effects of lomustine combined with Toca 511 + 5-FC in syngeneic orthotopic glioma models. Safety and survival were evaluated in immune-competent rat F98 and mouse Tu-2449 models comparing Toca 511 + 5-FC to lomustine + 5-FC or the combination of Toca 511 + 5-FC + lomustine. After intracranial implantation of tumor, Toca 511 was delivered transcranially followed by cycles of intraperitoneal 5-FC with or without lomustine at the first or fourth cycle.

resultsCoadministration of 5-FC with lomustine was well tolerated. In F98, combination Toca 511 + 5-FC and lomustine increased median survival, but "cures" were not achieved. In Tu-2449, combination Toca 511 + 5-FC and lomustine increased median survival and resulted in high numbers of cure. Rejection of tumor rechallenge occurred after treatment with Toca 511 + 5-FC or combined with lomustine, but not with lomustine + 5-FC. Mixed lymphocyte-tumor cell reactions using splenocytes from cured animals showed robust killing of target cells in an effector:target ratio-dependent manner with Toca 511 + 5-FC and Toca 511 + 5-FC + lomustine day 10.

conclusionThe combination of Toca 511 + 5-FC and lomustine shows promising efficacy with no additive toxicity in murine glioma models. Immunotherapeutic responses resulting in long-term survival were preserved despite lomustine-related myelosuppression.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsCytosine DeaminaseDisease Models, AnimalFemaleFlucytosineGenetic TherapyGenetic VectorsGlioblastomaImmunohistochemistryImmunotherapyLomustineMaleMiceRatsCytosine DeaminaseFlucytosineLomustine5-FChigh-grade gliomasimmunotherapylomustine (CCNU)Toca 511

Identifiers

PMID27166379
PMCPMC5035524
OpenAlexW2386241382

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.