Intra-Cerebrospinal Fluid Chemotherapy is New Direction in Pediatric Solid Tumors in Developing Countries

Research Article

J Blood Disord. 2019; 6(1): 1055.

Intra-Cerebrospinal Fluid Chemotherapy is New Direction in Pediatric Solid Tumors in Developing Countries

Babak A1, Zareifar S2*, Pouria S3 and Somayeh L1

1Department of Pediatric, Lorestan University of Medical Science, Iran

2Department of Pediatric, Shiraz University of Medical Science, Iran

33Department of Pediatric, Iran University of Medical Science, Iran

*Corresponding author: Soheila Zareifar, Department of Pediatric, Shiraz University of Medical Science, Shiraz, Iran

Received: December 04, 2019; Accepted: December 30, 2019; Published: December 31, 2019


Introduction: Intra-cerebrospinal fluid (CSF) chemotherapy defined chemotherapy drugs administration in the brain/spine fluid compartment for leptomeningeal metastases treatment in infilterative tumors such as leukemia and lymphoma routinely. This method was administered for adults since 20 years ago but there is a limited experience in children.

Material and Method: We used electronic search on the online medical database "PubMed" and other motor search-engines such as "Google Scholar” and selected all of articles about intra-CSF chemotherapy regimens in solid tumors.

Results: We collected original articles and review articles over 20 years, on the target .All of selected articles include intrathecal chemotherapy regimens in solid tumors in pediatrics and adult patients with leptomeningeal metastasis.

Conclusion: We introduce several intra-CSF chemotherapy regimens in solid tumors. This approach can be used in pediatrics with radiation limitation.

Keywords: Intrathecal chemotherapy; Leptomeningeal metastases; Solid tumors


Intra-cerebrospinal fluid (CSF) chemotherapy is chemotherapy drugs administration in the brain/spine fluid compartment, which can treat leptomeningeal metastases of infiltrative tumors (leukemia and lymphoma) since some years ago, but intra-CSF chemotherapy drugs administration during pediatric solid tumors treatment is unusual and there are limit experiences. This is a new insight and approach for fighting against leptomeningeal metastasis of solid tumors in cancerous children. This technique is available by 2 methods: 1.intratechally 2. intraventricular through ommaya reservoir. Co-administration of this technique with conventional chemotherapy in metastatic embryonic tumors among younger kids has good outcome. In this technique is tried to supply excessive doses of chemotherapy to the coating regions of the brain and cover sanctuary sites [1-3].

Intrathecal chemotherapy destroys subclinical leptomeningeal deposits and kill tumor cells floating in the cerebrospinal fluid, and prevent tumor seeding [4].

Efficacy of single or combined intracerebrospinal (ICSF) chemotherapy is a challenging and controversial issue. Some trials have shown no distinction among single-agent Methotrexate and combined regimen. Combination regimens may be have greater neurotoxicity than single ICSF chemotherapy [5].

Use of intraventricular ommaya reservoir has better protective effect than intrathecal chemotherapy against tumor cells.

This modality of treatment provides high concentration of the drug on the site of the tumor and has more harmful effects on the normal brain [6,7].

Thiotepa and methotrexate (MTX) is the one of the oldest chemotherapy drugs has administered intra-CSF in solid or hematopoetic malignancies. Thiotepa is cleared from CSF within a few minutes and has survival curves similar to those of MTX, but it is lesser neurotoxic than MTX. Leukoencephalopathy secondary to intraventricular excessive dose of methotrexate is a problematic event after long-term intra-CSF administration of MTX, but decreasing methotrexate dose infused into the fourth ventricle has lesser neurological deficits or toxicity.

Recently, new agents introduced for intra-CSF chemotherapy. A few studies define intra-CSF chemotherapy does no longer extend patient survival and considerably increases associated neurotoxicity’s [8].

Material and Method

We searched the Medline (PubMed) electronic database by using a broad search strategy. The studies were identified by utilizing a combination of MeSH terms, such as intra-CSF chemotherapy, intratechal chemotherapy, solid tumors and leptomeningeal metastasis. Two reviewers independently screened the list of references to assess their eligibility for inclusion in consultation with another reviewer. Collection, spanning over 20 years, was searched, as were recent issues of journals in which articles on the subject are most often found (2017-1995). The inclusion criteria were as follows:

1- The articles address an appropriate and clearly focused question

 2- The study was done to minimise bias

3- Identify all the relevant studies.

4- There are enough similarities between the studies selected to make combining them reasonable.

5- Publication date between 1995- 2017

6-Article in English

7- Peer-reviewed journals. In addition, an extensive personal literature.

Inclusion Criteria

Finally, 31 main articles were founded to form the basis for this mandatory narrative review.


A total of 31 publications (22 include and 67 exclude) during 1995-2017, met eligibility criteria for this review was based on successful experiences for intra-CSF chemotherapy on solid tumors.

We found some chemotherapy drugs for intra-CSF chemotherapy for solid tumors treatment in the literature and suggest two standard intrathecal chemotherapy regimens for pediatric solid tumors.


Majority of intra-CSF chemotherapy regimens in solid tumors were suggested for adult and pediatric during two decades.

Traditionally, intra-CSF drug regimen include 3 chemotherapeutic drugs (Methotrexate, Cytosine Arabinoside, and Thiotepa) administered through intratechal or intraventricular pathway [9].

Cytararabine is not effective for solid tumors but is useful in leukemic and lymphomatous meningitis. It is now available in liposome-encapsulated form (DepoCyt) that can be administered every 2 weeks rather than 2-3 times a week and results in a longer time to disease progression and higher quality of life than therapy with MTX [10].

Thiotepa can be use as the second line agent after MTX and cytarabine [11].

Intraventricular methotrexate is used for non-disseminated tumors that were absolutely resected. Five-year free survival after the addition of methotrexate is envisioned approximately 60%. Just 3-5% of systemically administered MTX penetrates the blood-brain barrier (BBB) at a half of-clearance time of 6 hours. Single intraventricular injection of MTX (6.25 mg/m2) can achieve healing awareness inside the lumbar area for 48 hours at a minimal systemic absorption (<0.1 µM ) [12].

In brain tumors, intraventricular methotrexate therapy was more acceptable and feasible and mostly well tolerated. In this method, infections were the most frequent complication. A higher cumulative dose of intraventricular methotrexate was associated with better survival [13].

Citation: Babak A, Zareifar S, Pouria S and Somayeh L. Intra-Cerebrospinal Fluid Chemotherapy is New Direction in Pediatric Solid Tumors in Developing Countries. J Blood Disord. 2019; 6(1): 1055. ISSN 2379-8009