Metronomics Global Health Initiative

the International School of Metronomic Chemotheray - ISMe

2019-07-18T14:40:06Z

We are delightred to e to introduce you “The International School of metronomic chemotherapy – ISMe”. This initiative is being lead by Dr. Marina Elena Cazzaniga.

ISMe's Core Faculty are all well recognized experts in the field of metronomic chemotherapy or are active participants of ongoing trials exploring new areas of research.

ISME has the aim to improve the knowledge in this particular type of treatment, its characteristic mechanisms of action, the most recent results in different types of cancer, as well as contributing to scientific exchange among physicians, clinicians and basic researchers involved in this field.
By improving the skills of all health professionals dealing with cancer patients, ISMe helps shorten the time needed to transfer knowledge from research centres to daily practice.
Last but not least, is that the School has no charging fees.
ISMe planned to start activities in 20198, providing independent, evidence based, patient-oriented education to health professionals, including clinical and medical oncologists, radiation therapists, surgeons, nurses, patients advocates and medical students on the topic of metronomic chemotherapy.
Due to unmet educational needs outside Europe, ISMe will include the Eurasia region, Mediterranean region, North and South Africa, Middle East, South-East Asia, and Central/South America as part of a wider “cultural Europe” in its educational activities.
Education will be delivered through e-learning activities.

ISMe is a distance learning school completely focused on spreading knowledge on metronomic chemotherapy, both at a pre-clinical and a clinical level.
Depending on location ISMe will provide web-based training (WBT), or computer-based training (CBT). ISMe Educational Program is composed of 12 different Modules. Each Module is organized and chaired by a Faculty Member, previously presented and approved by the Scientific Committee. Each Module can be attended separately from the others, even if the suggestion of the School is to attend each of them in sequence.
The training material consist of webinar recordings, pdf, literature and case studies.
The school permits to obtain EACCME® credits, as long as the attendee performs at least 10 out of 12 online modules and relative tests (multiple choice).

Here are the planned topic modules :
1. Pre-clinical data (1) – Robert Kerbel, Eddy Pasquier

2. Pre-clinical data (2) – Yuval Shaked, Bertolini Francesco, J Ciccolini

3. Pre-clinical data (3) – Guido Bocci, Maria Grazia Cerrito

4. Breast cancer (1) – neo&adjuvant – E. Munzone ,E. Montagna, L. Sven, M. Cazzaniga

5. Breast cancer (2) – metastatic– M. Cazzaniga, E. Petru , P. Sanchez-Rovira, E. Munzone

6. Lymphomas – Pediatric cancer – Nicolas André, Cox Christina, F. Berthold, J. Sterba

7. Colon and gastrointestinal cancers–Piotr Wysocki, Woo In Sook

8. Gynecologic cancers – Piotr Wysocki, Łukasz Kwinta, Pawel Potocki

9. Prostate Cancer – Camerini Andrea, Urban Emmenegger

10. Lung cancer – Camerini Andrea, Francesco Grossi

11. Nursing care –Marina Cazzaniga, Lourein Smit

12. Pharmacoeconomic – M. Cazzaniga, R. Umberto, P. Pantziarka, E. Pasquier

You can find the dedicated website here

3rd Karton Kamen-MGHI Prize : call for abstracts

2017-11-21T08:20:05Z

We are very proud to launch the call for abstract for the Third Barton Kamen-MGHI prize

The prize is given in honor of Pr. Barton Kamen, pediatric oncologist, pioneer in the field of metronomic chemotherapy. Barton Kamen has been one of the leading force that has kept the field of metronomics alive when it was facing resistance/skepticism from clinicians. Barton has also been a source of inspiration for clinical colleagues, scientists and mentored many junior scientists. Barton Kamen was also the first very MGHI ambassador. Through this prize, we wish to acknowledge his critical role for the field of metronomics and maintain his legacy alive by rewarding a clinician or a scientist working in the field of metronomics. Priority will be given to work focusing on children living in low and middle countries

This prize is awarded to the author of the best submitted scientific article. The jury can also propose candidate. The winner will present his work and receive the prize during the 6th Metronomic Meeting that will take place in Grand Rapids in May 2018 (click here for more information) All accepted abstracts will be published on the MGHI website.

The dead-line for submission is 01/03/2018 Results will be given by email before the 10th of April.

For more information conctact: metronomicsghi@gmail.com

Abstract Requirements and Guidelines

Formatting Tips:

Abstracts must be submitted in English by email at metronomicsghi@gmail.com. Each abstract should consist of four separate paragraphs. These should be labeled Background, Methods, Results, and Conclusions. Each abstract should, briefly and concisely, describe the problem or issue being addressed, how the study was performed, the salient results or findings, and what the authors conclude from these results.

Abstracts are not to exceed 200 words, excluding title and authors.The length should correspond to approximately 1 pages, single-spaced, in a Word document Abstract titles are restricted to 25 words.. You will type the title, authors and keywords into individual fields, separately from the body of the abstract.

Abstracts must clearly define the objectives, status, methodology, findings, and significance of the investigation or stud

How Abstracts are Judged and Assigned

Abstracts submitted for presentation will be reviewed by the Scientific Committee in April. Notification of acceptance and schedule information will be sent in APRIL. Abstracts will be judged according to four criteria: scientific merit, originality, interest for metronomic

Drug repositioning- Frontiers in Oncology-call for papers

2017-01-13T11:22:18Z

Pan Pantziarka for the Anticancer Fund and Nicolas André from the Metronomic Global Health Initiative are organizing a Research Topic titled “Drug Repurposing” to be published in Frontiers in Medicine.

Drug repurposing, also known as drug repositioning, is a strategy that seeks to reuse existing, licensed medications for new medical indications, often in diseases with very different profiles to that for which the drug was originally developed. Repurposing offers a number of significant advantages in comparison with de novo drug development. These include the availability of extensive pharmacokinetic, pharmacodynamic and safety data, (with data on both common and rare adverse events) and an understanding of relevant molecular targets and mechanisms of action.

Additionally the repurposing of generic medications is appealing at a time when economic pressures are negatively impacting health systems globally. The potential for cheap generic medications to tackle cancer and other serious medical conditions in low and middle income countries is particularly appealing. The combination of drug repurposing and metronomic chemotherapy, often termed metronomics, is particularly appealing in this respect. However, more widespread adoption of the repurposing strategy is often hampered by a lack industry engagement and poor financial incentives. Therefore, while the advantages are clear, there are many challenges to overcome in order to show clinical efficacy, which is the most important criterion by which repurposing should be judged.

This Research Topic provides a focus on drug repurposing, particularly in a clinical context. Potential articles will focus on translational and clinical studies, case reports, trial rationales and so on. An additional focus will be on regulatory and institutional issues related to repurposing, including drug licensing, financial disincentives and other factors associated with translating trial results to clinical practice.

The project homepage with a full description of this project can be found here

Important Note: All contributions to this Research Topic must be in line with the scope of the specialty and field to which they are submitted, as defined in their mission statements. Manuscripts discovered during any stage of peer review to be outside of the scope may be transferred to a suitable section or field, or withdrawn from review.

The 2nd Barton Kamen-MGHI Prize has been attributed to Pr G. Saulnier-Sholler : DFMO in Neuroblastoma

2016-05-09T16:09:37Z

The Second Barton Kamen-MGHI Prize has been attributed to Pr Giselle Saulnier Sholler, during the 5th Metronomic Meeting that took place in Mumbai from the 6th to 8th of MAY 2016. Pr G. SAULINER is currently
Director of Pediatric Oncology Research
Head of the Pediatric Oncology Translational Research Laboratory
Helen DeVos Children's Hospital, Grand Rapids, MI, USA.
Associate Professor, Michigan State University College of Human Medicine
Chair of the Neuroblastoma & Medulloblastoma Translational Research Consortium

The prize was given to her in recognition of her work on DFMO in neuroblastoma.

Read more about DFMO and the NMTCR here.

Second Barton Kamen-MGHI prize: call for abstract

2016-01-27T13:47:32Z

We are very proud to launch the call for abstract for the Second Barton Kamen-MGHI prize

The prize is given in honor of Pr. Barton Kamen, pediatric oncologist, pioneer in the field of metronomic chemotherapy. Barton Kamen has been one of the leading force that has kept the field of metronomics alive when it was facing resistance/skepticism from clinicians. Barton has also been a source of inspiration for clinical colleagues, scientists and mentored many junior scientists. Barton Kamen was also the first very MGHI ambassador. Through this prize, we wish to acknowledge his critical role for the field of metronomics and maintain his legacy alive by rewarding a clinician or a scientist working in the field of metronomics. For the first prize, priority will be given to work focusing on children living in low and middle countries

This prize is awarded to the author of the best submitted scientific article. The winner will present his work and receive the prize during the 5th Metronomic Meeting that will take place in Mumbai in May 2016 (click here for more information) All accepted abstracts will be published on the MGHI website.

The dead-line for submission is 1/04/2016 Results will be given by email before the 10th of April.

For more information conctact : metronomicsghi@gmail.com

Abstract Requirements and Guidelines

Formatting Tips:

Abstracts must clearly define the objectives, status, methodology, findings, and significance of the investigation or stud

How Abstracts are Judged and Assigned

the MGHI metronomics in LMIC survey

2016-01-03T09:25:00Z

MGHI is launching an international survey to know more about the use of metronomic chemotherapy and drug repositioning to treat children with cancer in LMIC.
The questioned have been developed by Dr Gabriel Revon-Rivière and Dr Nicolas André.
We aim at sending the survey in central and South America, Africa (GFAOP), Iran, Uganda, Tanzania and India.
This survey has 18 items, it is to be answered on-line and requires 10 minutes to be filled.
You may be contacted soon by email.

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Metronomic therapy can increase quality of life during paediatric palliative cancer care, but careful patient selection is essential.

2016-01-01T10:32:00Z

Porkholm M, Toiviainen-Salo S, Seuri R, Lönnqvist T, Vepsäläinen K, Saarinen-Pihkala UM, Pentikäinen V, Kivivuori SM from the Division of Hematology-Oncology and Stem Cell Transplantation, the Division of Child Neurology, the Division of Pediatrics and the Department of Pediatric Radiology from the University of Helsinki and Helsinki University Hospital, Helsinki, Finland. have just published an article entitled "Metronomic therapy can increase quality of life during paediatric palliative cancer care, but careful patient selection is essential." in Acta Paediatrica.

They report on 17 children with refractory or high-risk malignancies who were treated with a maintenance therapy that consisted of metronomic thalidomide, etoposide and celecoxib. The endpoints of the study were overall and progression-free survival, changes in the Karnofsky-Lansky scores from baseline to the end of the study therapy and radiological responses.
The median overall survival after the start of the study therapy was 6.2 months (range 2.0-57.7) and the six, 12 and 24-month survival rates were 59%, 18% and 18%, respectively. The median progression-free survival was 3.2 months (range 0.3-17.8). The Karnofsky-Lansky scores increased significantly during the study therapy (p=0.02), with 35% of the patients having a transient improvement in their clinical status. Radiologically, one partial response and two disease stabilisations were encountered. Grade III-IV adverse events occurred in 76% of the patients.
This report highlight that metronomics can increase the quality of life during palliative care for childhood cancer, but requires careful patient selection to minimise the risk of serious adverse events.

You can access the full text on the website of the journal here

Update about the Moroccan Society of Pediatric Hematology/Oncology Phase II metronomic trial.

2015-07-10T10:47:33Z

Cure rates in pediatric cancer can reach 80% in high income countries (HIC). However, 80% children are living low income countries where cure rates often don't exceed 35%. Children with metastatic, unresectable, or recurrent cancer continue to have poor prognosis and the treatment of these patients with second-line intensive or experimental treatments with new expensive drugs, as it is done in HIC nonrealistic option in most of the African countries.

In Morocco, we have previously reported cases of disease stabilization and/or second complete remission in children with recurrent or relapsed malignant disease (SIOP Africa Ghana 2005) under prolonged low dose of cyclophosphamide treatment. Besides, a study from Mali, another LMIC African country, reported the efficacy and safety of a vincristine/cyclophosphamide/methotrexate MC regimen given to children with refractory cancer of various tumor types. These findings led pediatricien from Morroco to look closely at the concept of metronomic chemotherapy (MC) for children with cancer treated in Morocco.

Pr Laila Hessissen and Pr Maria El Kababri with the help of MGHI therefore initiated in 2014 a prospective multicentre metronomic phase II trial with a cyclophosphamide, etoposide, and valproic acid combination in children with either a relapsing/refractory tumors or a very advanced disease. This project is conducted by The Moroccan Society of Pediatric Hematology/Oncology with the financial support of the Lalla Salma Foundation Prevention and Treatment of Cancer.

Intravenous Etoposide is used by oral route because oral form is not available in Morocco.
The primary objective of the protocol is to evaluate the anti-tumor effect defined by:
– Progression free survival (PFS) after 4 months (4 cycles), 8 and 12 months of treatment.
– Response rate after 4 months, 8 and 12 months of treatment.
The secondary objectives are:
– Evaluate the tolerance of treatment
– Evaluate the quality of life (at D0 and every 4 months)
– Evaluate the analgesic consumption and the transfusion requirements

The study is ongoing and 20 patients from 3 out of the 4 Moroccan pediatric oncology centers have been included so far. Tolerance of treatment and compliance are excellent.

Treated patients:
– Ewing : 4 patients
– Osteosarcoma : 3
– Neuroblastome : 2
– Rhabdomyosarcoma : 4
– MGT : 2
– Nephroblastoma : 2
– UCNT : 1
– Medulloblastoma : 1
– STS : 1

Dose-Finding of Propranolol in combination with metronomic fixed oral cyclophosphamide based on Bivariate efficacy-tolerability outcome in patients with locally advanced or metastatic angiosarcoma : A collaborative and innovative phase I-II sequential trial

2015-02-26T11:07:27Z

The Pr Sébastien Salas from the Adult Oncology Unit, CHU La Timone, AP-HM, Marseille, France has obtained funding for the PROPAN study (Dose-Finding of Propranolol in combination with metronomic fixed oral cyclophosphamide based on Bivariate efficacy-tolerability outcome in patients with locally advanced or metastatic angiosarcoma : A collaborative and innovative phase I-II sequential trial ).

Adrenergic processes stimulated by epinephrine and neorepinephrine drive the development of tumor growth and metastatis. Beta-adrenergic receptor (BAR) antagonists have shown efficacy against melanoma, breast cancer and prostate cancer. The non-specific BAR inhibitor propranolol has been utilized as the gold standard treatment in pediatric patients with benign infantile hemangioma which express high levels of beta adrenergic receptors potentially explaining their sensitively to propranolol. BAR have been shown to be expressed across a diverse panel of vascular tumors, with the highest expression in malignant vascular tumors including angiosarcomas. Several reports indicate positive results from beta-blockade in patients with moderately threatening vascular tumors. It remains to be determined if more malignant vascular tumor such as the angioasarcomas are susceptible to propranolol. Besides, due to the lack of adequate therapies for angiosarcomas (doxorubicin or paclitaxel and finally cyclophosphamide in third line) and to the poor prognosis of this rare and agressive tumor, there is a strong need for the development of treatments against this tumor type.
Recently using a panel of angiosarcoma cell lines, Stiles et al. demonstrate that beta-adrenergic inhibition blocks cell proliferation and induces apoptosis in a dose dependent manner. Moreover, using in vivo tumor models they demonstrate that propranolol shows remarkable efficacy in reducing the growth of angiosarcoma tumors.
Based on these proofs of mechanisms in vitro and in vivo and due to the well established safety propranolol in humans, we propose to determine among a wide range of propranolol dose (80 mg/d ; 120 mg/d and 160 mg/d) the optimal one based on bivariate efficacy-toxicity outcome in patients with angiosarcoma treated by cyclophosphamide.
Because these these 2 agents have different pharmacological mechanisms, the aim is to determine the optimal dose of propranolol having the best systemic cardiovascular tolerability and the best potential antiangiogenic effect in addition with cyclophosphamide. Due to recent preclinical papers demonstrating the selective cytotoxicity and tumor suppressive ability of beta adrenergic inhibition on angiosarcoma in dose dependant manner, we propose here for the first time to assess the synergy of propranolol and fixed dose of oral cyclophosphamide among patients with advanced angiosarcoma, using an innovative design modeling both toxicity and efficacy outcomes (dose finding combined phase I-II sequential trial using a bivariate continual reassessment method). Because this tumor is very rare leading to a limited number of patients and because an efficient therapeutic is lacking, this design is particular of interest in order to determine more quickly the potential dose of propranolol to be tested in the pivotal phase III.

This trial will be a joint effort from the GSF/GETO, the SFCE and MGHI and will include adults and teenagers from French centers.
In this dose-finding design up to 24 patients will be required to find the dose level satisfying the requirements in terms of toxicity and efficacy.
The study shall be opened for recruitement by mid 2015.

First Barton Kamen-MGHI prize : Modified COMBAT (Combined Oral Metronomic Biodifferentiating Antiangiogenic Treatment) therapy in poor prognosis pediatric malignant brain tumors

2014-07-18T09:08:00Z

The first Barton Kamen-MGHI Prize has been attributed to Pr Shripad Banavali following the submission of the following abstract. The work will be presented during the 4th Metronomic Meeting that will take place in Milano on the 24th and 25th of June 2014.
Dr Shripad D. Banavali is Professor & Head, Dept. of Medical & Pediatric Oncology
Vice President (India), Asian Cellular Therapy Organization and Coordinator, TMC-Rural Outreach Program in Mumbai

MODIFIED COMBAT (COMBINED ORAL METRONOMIC BIODIFFERENTIATING ANTIANGIOGENIC TREATMENT) THERAPY IN POOR PROGNOSIS PEDIATRIC MALIGNANT BRAIN TUMORS - IS THERE A ROLE?

CHINNASWAMY GIRISH, Prasad Maya, Vora Tushar, Arora Brijesh, Sridhar Eppari, Gupta Tejpal, Moiyadi Ali, Jalali Rakesh, Kukure Purna, Banavali Shripad

Background: The outcome of children with recurrent/high risk malignant brain tumors continues to be poor with conventional modalities of therapy. Metronomic therapy (COMBAT) has been found to be beneficial in many disseminated and aggressive pediatric solid tumors. We evaluated the impact (efficacy and toxicity) of this strategy in children with poor prognosis malignant brain tumors.

Methods: Children deemed to have a poor risk malignant brain tumor (by histology, site, metastatic status) were started on modified COMBAT regimen after completion of conventional therapy. Relapsed high grade tumors were also included. The treatment strategy consisted of the COMBAT regimen which includes low dose temozolomide, etoposide, sodium valproate and 13-cisretinoic acid administered in 12-weekly cycles. All children were followed up at 3 monthly intervals with clinical evaluation and MR imaging.

Results: Thirty four children were started on Modified COMBAT therapy between the year 2010-2013 and 32 were available for evaluation. The median age of the study population is 10 years with a male:female ratio being 2:1. Among the 32 patients, 13(40.6%) had relapsed/progressive medulloblastoma, 7(21.9%) had metastatic/recurrent PNET(supratentorial), 7(21.9%) had recurrent anaplastic ependymoma and 5(15.6%) were diagnosed with diffuse pontine glioma. 23/32 (71%) of patients showed a response(SD/PR/CR) to therapy while 9(28%) of patients continued to progress with no response documented. Toxicity included grade III/IV cytopenia in 2 patients and 1 patient developed myelodysplastic syndrome. Isotretinoin skin toxicity was noted in majority and was manageable with topical interventions. In the final analysis 62.5%(20) of patients had progressed with median time to progression being 9 months (2-44 months) while 37.5%(12) patients had shown a positive sustained response.

Conclusion: The modified COMBAT regimen is a feasible, well tolerated and effective treatment option for children with high risk or metastatic brain tumours. The data is a retrospective analysis and hence a prospective study to evaluate this strategy systematically is warranted.